bromochloroacetic-acid and Esophageal-Neoplasms

The palmoplantar epidermis is a specialized area of the skin that undergoes high levels of mechanical stress. The palmoplantar keratinization and esophageal cancer syndrome, tylosis with esophageal cancer, is linked to mutations in RHBDF2 encoding the proteolytically inactive rhomboid protein, iRhom2. Subsequently, iRhom2 was found to affect palmoplantar thickening to modulate the stress keratin response and to mediate context-dependent stress pathways by p63. iRhom2 is also a direct regulator of the sheddase, ADAM17, and the antiviral adaptor protein, stimulator of IFN genes. In this perspective, the pleiotropic functions of iRhom2 are discussed with respect to the skin, inflammation, and the antiviral response.

Topics: ADAM17 Protein; Animals; Carrier Proteins; Dermatitis; Disease Models, Animal; Epidermis; Esophageal Neoplasms; Foot; Gene Expression Regulation; Hand; Host Microbial Interactions; Humans; Intracellular Signaling Peptides and Proteins; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Mice; Mice, Knockout; Mutation; Signal Transduction; Skin Diseases, Viral; Transcription Factors; Tumor Suppressor Proteins

Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.

Topics: Aged, 80 and over; Atrophy; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Keratins; Male; Mucin-5B; Neoplasms, Glandular and Epithelial; Retrospective Studies

Adenoid cystic carcinoma (ACC) commonly originates in the major salivary glands and respiratory tract, but extremely rarely in the oesophagus. We report the surgical and pathologic findings of a primary ACC of the oesophagus in a 59-year-old woman, and review the management options of this tumour.

Topics: Actins; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Esophageal Neoplasms; Female; Humans; Keratins; Middle Aged

This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

Topics: alpha-Fetoproteins; Antigens, CD19; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Lewis X Antigen; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Protein Precursors; Prothrombin; Stomach Neoplasms

Adenocarcinoma of the upper esophagus arising in heterotopic gastric mucosa is a rare tumor, with only 15 cases reported to date. We report a case in a 61-year-old man complaining of dysphagia. The upper endoscopy revealed that the tumor measured 3 cm and was 22 cm distant from the incisivors. A hiatal hernia with erosive esophagitis of the distal esophagus was present. On microscopic examination the tumor corresponded to a poorly differentiated adenocarcinoma immunoreactive for cytokeratin (CK) 7 and p53. The surrounding heterotopic gastric mucosa contained foci of intestinal metaplasia immunoreactive for CK7 in the surface epithelium and the entire glands and CK20 in the superficial epithelium and superficial glands. The CK7 and p53 positivity that we observed is very common in Barrett's adenocarcinomas. Moreover, intestinal metaplasia in heterotopic gastric mucosa shows the same CK7/CK20 pattern as specialized Barrett's mucosa. These common features shared by adenocarcinomas of the upper esophagus arising in heterotopic gastric mucosa and adenocarcinoma of the lower esophagus developing on Barrett's mucosa suggest that those two types of cancer have a common pathogenesis, related to gastroesophageal reflux disease.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Choristoma; Combined Modality Therapy; Esophageal Neoplasms; Fatal Outcome; Gastric Mucosa; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Tumor Suppressor Protein p53

Several case reports have emphasized that esophageal carcinoid tumors are associated with a poor prognosis. To expand our knowledge about the pathology and biologic behavior of these rare tumors, we reviewed the clinicopathologic and immunohistochemical findings of four cases of primary esophageal carcinoid. The age of the patients ranged from 48 to 82 years (mean 63 years; median 61 years). The lower segment of the esophagus was involved in two cases and the mid segment was involved in one case. The sizes of the tumors ranged from 0.3 cm to 3.5 cm. Two tumors were confined to the lamina propria and two invaded into the muscular wall. Two tumors appeared polypoid, whereas the remaining two were incidental findings and associated with adenocarcinoma arising in a background of Barrett esophagus. The adenocarcinoma was superficially invasive in one case, whereas it penetrated the muscular wall in the other. All four carcinoid tumors were immunoreactive with chromogranin and synaptophysin. There was focal expression of serotonin in two cases, glucagon in one case, and pancreatic polypeptide in one case. Endocrine cell hyperplasia was noted in both the Barrett esophagus and the invasive adenocarcinoma. One patient died secondary to postoperative pneumonia. Three patients are alive and disease free at 1, 6, and 23 years status post therapy. None of the patients had metastatic disease. These findings show that esophageal carcinoids are associated with a favorable prognosis. They arise in two settings: (1) a single large polypoid tumor or (2) an incidental finding and in association with adenocarcinoma arising in the background of Barrett esophagus. The presence of endocrine cell hyperplasia in the Barrett mucosa and the adenocarcinoma supports the hypothesis that these lesions arise from a common stem cell.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Barrett Esophagus; Carcinoid Tumor; Chromogranins; Esophageal Neoplasms; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pancreatic Polypeptide; Polyps; Prognosis; Synaptophysin

Esophageal squamous cell carcinoma in situ (SCCIS) with diffuse pagetoid features is a recently recognized rare variant of squamous cell carcinoma. A histopathological study of a specimen from a 70-year-old male Japanese patient is reported. The patient died of respiratory failure due to rapidly progressing metastatic pulmonary tumors of unknown origin 73 days after the onset of hemosputum. Autopsy disclosed widespread metastasis of choriocarcinoma in the absence of tumors of the testes or other common sites of germ cell tumors. Elevation of human chorionic gonadotropin (hCG-beta) levels was later detected in the stored serum. Serial histological evaluation of the entire esophagus revealed a small primary site of choriocarcinoma in a background of diffuse SCCIS, mainly of pagetoid type, accompanied by several small foci of submucosally invasive squamous cell carcinoma and primary mucoepidermoid carcinoma. These stimulated nodal metastasis independently of the choriocarcinoma. The SCCIS did not alter the gross mucosal appearance. This is the first reported case of diffuse pagetoid SCCIS combined with choriocarcinoma. Morphological findings and previous studies suggest that the extensive SCCIS of the esophagus resulted from pagetoid spread of tumor cells. The invasive squamous cell carcinoma, mucoepidermoid carcinoma and choriocarcinoma are suggested to have originated from the overlying SCCIS.

Topics: Aged; alpha-Fetoproteins; Autopsy; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Esophageal Neoplasms; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Paget Disease, Extramammary; Tissue Polypeptide Antigen

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Bone Neoplasms; Carcinoembryonic Antigen; Esophageal Neoplasms; Humans; Keratins; Lymphatic Metastasis; Neoplasm Metastasis; Reverse Transcriptase Polymerase Chain Reaction

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Cardia; Epithelium; Esophageal Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins

Palmoplantar keratosis is a frequent hereditary disorder of keratinization in humans that have been classified into diffuse, punctate and focal forms according to the pattern of hyperkeratosis on the pal and soles. Various clinically, histopathologically and genetically distinct phenotypes can be diagnosed. Diffuse palmoplantar keratodermas can be further subdivided by the presence of epidemlysis on histopathology into epidermolytic form and non-epidermolytic form. The late onset non-epidermolytic palmoplantar keratoderma was found associated with oesophageal cancer. The causative locus designated as TOC(Tylosis with oesophageal cancer) mapped to a small region on chromosome 17q25. Frequent allelic loss was found overlapping the region in sporadic oesophageal, ovarian and breast cancers. Positional cloning and candidate gene analysis will allow identification and characterization of the TOC gene which may also be implicated in cancer development.

Topics: Chromosome Mapping; Chromosomes, Human, Pair 17; Cytoskeletal Proteins; Desmoplakins; Esophageal Neoplasms; Humans; Keratins; Keratoderma, Palmoplantar; Loss of Heterozygosity; Phenotype

Topics: Bone Marrow; Bone Marrow Examination; Bone Marrow Neoplasms; Breast Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Stomach Neoplasms; Uterine Cervical Neoplasms

A clinically and genetically heterogeneous group of disorders, known collectively as the palmoplantar keratodermas, are unified by the phenotypic characteristic of a thickening of the skin over the palms and soles. Although spectacular progress has been made in understanding the basis of many genodermatoses, the genetic defects causing many of the keratodermas are still largely unknown. These unusual phenotypes are beginning to capture the attention of investigators in epidermal biology, and several compelling lines of evidence point to the cornified cell envelope and structural components of the desmosome as potential underlying targets of disease. It is anticipated that understanding the molecular basis of the keratodermas will underscore the importance of the integrity of the cell envelope and the desmosome, and provide new insights into the mechanisms of epidermal differentiation and related disorders.

Topics: Animals; Autoantibodies; Cell Differentiation; Cell Membrane; Desmosomes; Epidermal Cells; Esophageal Neoplasms; Genetic Linkage; Humans; Keratins; Keratoderma, Palmoplantar; Keratoderma, Palmoplantar, Diffuse; Keratosis; Membrane Proteins; Mice; Mice, Transgenic; Pemphigus; Protein Precursors

We report a case of spindle-cell adenosquamous carcinoma of the esophagus. This represents the third case in the worldwide literature in which an esophageal polypoid tumor contains adenosquamous carcinoma rather than the usual squamous cell carcinoma in addition to a prominent spindle-cell element. The spindle-cell component displayed positive immunoreaction for both keratin and vimentin, as expression of bidirectional differentiation within a single neoplasm.

Topics: Adenocarcinoma; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Vimentin

Merkel cell carcinomas (MCC) were compared to small cell carcinomas of the lung (SCCL) and oesophagus (SCCO). Most MCC were of the intermediate cell type while SCCL and SCCO were usually of the small cell type. Only MCC of trabecular type could be separated from SCCL and SCCO by means of histopathological examination alone. All MCC (25) stained with cytokeratin CAM 5.2, 20 of which in a "paranuclear globular" or combined "paranuclear globular"/diffuse pattern while 17 MCC stained with cytokeratin AE1/AE3. Cytokeratin CAM 5.2 reacted with 60 percent of the SCCL and 86 percent of the SCCO, and cytokeratin AE1/AE3 with 33 and 28 percent respectively. Neurofilament stained 17 MCC in a "paranuclear globular" pattern but none of the SCCL and SCCO. All MCC with a diffuse staining pattern for cytokeratin CAM 5.2 were negative for neurofilament. The results of this study and review of the literature indicate that in most instances Merkel cell carcinoma can be separated from other SCC, pulmonary as well as extrapulmonary, by means of histopathological and, above all, immunohistochemical examinations.

Topics: Antigens, CD; Antigens, Differentiation; Carcinoma, Merkel Cell; Carcinoma, Small Cell; Esophageal Neoplasms; Histocompatibility Antigens; Humans; Intermediate Filament Proteins; Keratins; Leukocyte Common Antigens; Lung Neoplasms; Membrane Glycoproteins; Mucin-1; Neurofilament Proteins; Phosphopyruvate Hydratase; S100 Proteins

The DNA content of oesophageal tumour cells is a prognostic factor in untreated patients. To investigate whether DNA ploidy is useful to select patients for neoadjuvant therapy it is of interest to develop a method allowing reliable flow cytometric analysis of the DNA content of tumour cells obtained by forceps biopsy during endoscopy before start of therapy.. Freshly frozen forceps biopsy samples from 30 patients with oesophageal cancer were disaggregated. DNA was stained with propidium iodide and ploidy was determined by flow cytometry. To enhance sensitivity epithelial cells were simultaneously labelled with anti-cytokeratin antibodies. Results were compared with image analysis. To evaluate the sampling error, parallel measurements were done in 10 patients by image analysis on forceps biopsies obtained during endoscopy before surgery and on the resected tumour.. The sensitivity to detect aneuploidy was lower for standard flow cytometry than for image analysis (13 versus 33%). The overall sensitivities were identical using a double labelling technique with additional cytokeratin-staining of the epithelial cells, but divergent results were obtained in 2 cases, where detection of aneuploidy was either possible with image analysis or with double labelling flow cytometry only. DNA content of samples gained by forceps biopsies and surgically resected tumours was concordant in 8 of 10 cases. In 2 patients, aneuploidy was detected only in the surgically resected tumour but not in the pre-operatively obtained forceps biopsies.. A flow cytometric method for routine determination of the DNA ploidy of cells obtained by forceps biopsies from patients with oesophageal cancer was developed and evaluated against image analysis. The technique allows the prediction of DNA content before tumour resection, and might be used for optimising therapy and the patient's quality of live.

Topics: Adenocarcinoma; Aneuploidy; Carcinoma, Squamous Cell; Cell Death; Diploidy; DNA, Neoplasm; Endoscopy, Digestive System; Epithelial Cells; Esophageal Neoplasms; Esophagectomy; Flow Cytometry; Gene Expression Regulation, Neoplastic; Humans; Image Processing, Computer-Assisted; Keratins; Mathematical Computing; Microscopy, Fluorescence; Ploidies; Predictive Value of Tests; Prognosis

The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging.. The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining.. Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node-negative and nonsentinel lymph node-positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23).. Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node.

Topics: Aged; Carcinoma; Esophageal Neoplasms; Esophagectomy; False Negative Reactions; Female; Humans; Immunochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Rhenium; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Technetium Compounds

Micrometastasis (MM) and tumor cell microinvolvement (TCM) in the lymph node were immunohistochemically evaluated using the cytokeratin (CK) antibody between a surgery group (n=20; 929 lymph nodes) and a chemotherapy group (n=20; 1052 lymph nodes). The incidence of MM+/-TCM in the surgery and chemotherapy groups was 50.0 (10/20) and 55.0% (11/20), respectively. Limiting the analysis to TCM alone revealed that the incidence in the chemotherapy group (10.0%; 2/20) was significantly lower than that in the surgery group (40.0%; 8/20; P=0.032). Preoperative chemotherapy in this regime was not effective, except for some patients with TCM alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Leucovorin; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Survival Rate; Treatment Outcome

To study the expression of keratin 19, 20 (K19, K20) in different tumor cell lines and tumor tissues and its clinical implication.. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was employed to examine the specific expression of K19 and K20 mRNA in eleven tumor cell lines and 33 corresponding tumor tissue specimens.. The expression of K19 mRNA was detected in 4 kinds of tumor cell lines and all tumor tissues examined, but the magnitude of expression differed, with a difference ranging from 1.7 to 10 folds for the same type of cancer. In some patients, the level of expression was as low as 12% of the positive control. K20 mRNA expression was negative for lung and esophageal tumor cell lines and the corresponding carcinoma specimens. In one of 6 bladder cancer specimens and in 4 of 5 colorectal cancer tissues, K20 expression was positive, at a level of 41%-77% of the positive control. There was no expression of K20 in bladder tumor cell line EJ1 and colorectal tumor cell line SW480.. These results demonstrate that K19 and K20 may be used as a valuable marker for detecting circulating cancer cells, but the low level of expression in some cases of carcinoma would probably result in false negative results.

Topics: Biomarkers, Tumor; Colorectal Neoplasms; Down-Regulation; Esophageal Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Lung Neoplasms; Neoplasms; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured; Urinary Bladder Neoplasms

While most resection specimens from patients with neoadjuvantly treated esophageal squamous cell carcinoma show therapy-related changes in the form of inflammation and fibrosis, others harbor a florid foreign body-type giant cell response to keratin debris. The purpose of our study was to perform a detailed clinicopathologic analysis of these histologic types of treatment responses and correlate these findings with patient outcome. Clinical and pathologic parameters from 110 esophagogastrectomies were recorded and analyzed. Two main types of histologic responses were observed: inflammatory-predominant response (59%) and florid foreign body-type giant cell response to keratin (41%). Irrespective of cG, cTNM, and amount of residual cancer, florid foreign body-type giant cell reaction was predominantly noted deep within the esophageal wall, while the inflammatory response was restricted to the mucosa, submucosa, and inner half of muscularis propria. Patients with foreign body-type giant cell response showed significantly better overall survival compared with the inflammatory response group (log-rank test P=0.015). Florid foreign body-type giant cell response was the only factor associated with improved survival in a multivariable analysis for overall survival (hazard ratio=0.5; 95% confidence interval=0.3-1.0; P=0.038), but not in the model for disease-specific survival, whereas ypTNM stage II was the only significant risk factor for disease-specific survival in multivariable analysis (hazard ratio=3.4; 95% confidence interval=1.0-11.2; P=0.047). Our results suggest that in addition to the College of American Pathologists Tumor Regression Score and ypTNM stage, subtype of histologic response to therapy may represent another prognostic marker for neoadjuvantly treated esophageal squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chemotherapy, Adjuvant; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Female; Gastrectomy; Granuloma, Foreign-Body; Humans; Keratins; Male; Middle Aged; Neoadjuvant Therapy; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Only few studies examined the prognostic effect of tumor budding in esophageal adenocarcinomas so far. However, different quantification approaches were used, so results cannot be directly compared. Recently, the International Tumor Budding Consensus Conference (ITBCC) published consensus criteria for the evaluation of tumor budding in colorectal cancer, which we applied in our study. Hematoxylin and eosin (H&E) and cytokeratin (AE1/AE3) stained whole tissue slides of 104 resected esophageal adenocarcinomas were evaluated. The mean count of tumor buds was analyzed in one high power field according to the ITBCC criteria and assigned to budding groups Bd1-3. Tumor budding was significantly associated with a worse overall survival. Regardless of the quantification approach, an increased number of tumor buds was significantly associated with reduced overall survival (OS) (H&E: HR = 1.05 (95% CI 1.029-1.073), p < 0.001; cytokeratin: HR = 1.073 (95% CI 1.045-1.101), p < 0.001). In multivariable analysis tumor budding according to ITBCC criteria on H&E stained slides was an independent prognostic factor. Tumor budding, according to ITBCC criteria, is an independent prognostic factor in resected esophageal adenocarcinoma. Prospective studies using ITBCC criteria are useful in the near future to validate our results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Movement; Esophageal Neoplasms; Esophagectomy; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow; Esophageal Neoplasms; Gene Expression; Humans; Immunohistochemistry; Keratins; Leukemia; Lung Neoplasms; Male; Neoplasms, Second Primary; Radiotherapy

Topics: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Humans; Keratins; Squamous Cell Carcinoma of Head and Neck

Tumor budding is known predictors of lymph node metastasis from esophageal squamous cell carcinoma. However, it is not easy to detect such small cell clusters on hematoxylin-eosin (HE) staining. Therefore, we evaluated tumor budding using immunohistochemistry (IHC) for epithelial cell markers.. We analyzed tumor budding in 50 cases of superficial esophageal squamous cell carcinoma. We evaluated the impact of clinicopathological factors and tumor budding to predict lymph node metastasis. A total of 565 tumor sections were assessed using HE staining and IHC for cytokeratin 5/6.. Based on receiver operating characteristic curves, the cut-off values for high-grade tumor budding evaluated using HE staining or IHC were 2 and 11, respectively. High-grade tumor budding evaluated using HE staining (P = 0.007) and IHC (P ≤ 0.001) were significantly correlated with lymph node metastasis. For tumors with pT1a-MM to pT1b-SM1, high-grade tumor budding evaluated using IHC was correlated with lymph node metastasis (P = 0.050).. Tumor budding was significantly associated with lymph node metastasis. The optimal cut-off values of tumor budding on HE staining and tumor budding on IHC were 2 and 11, respectively. Even though both tumor budding on HE staining and tumor budding on IHC were significantly associated with lymph node metastasis, tumor budding on IHC tend to be more associated with lymph node metastasis.

Topics: Aged; Aged, 80 and over; Epithelial Cells; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Predictive Value of Tests; Retrospective Studies; ROC Curve; Staining and Labeling; Tumor Burden

Regional lymph node metastases in patients with carcinoma of the esophagogastric junction (EGJ) are an important prognostic factor. According to the tumor, node, and metastasis classification, isolated tumor cells (ITCs) are single tumor cells or small clusters of tumor cells not exceeding 0.2 mm. Tumor clusters >0.2 mm are classified as metastases. The significance of lymph nodes with ITCs is unclear, although not contributing to the pN category. The aim of this study was to determine the prevalence of regional lymph nodes with ITCs on the primary hematoxylin and eosin-stained slide and to examine how often deeper sections reveal a true metastasis. The study included surgical specimens of 126 patients with adenocarcinoma of the EGJ. Lymph nodes with ITCs were identified. Additional sections were cut and stained with hematoxylin and eosin and with cytokeratin. All slides were evaluated for the presence of tumor cells, and it was determined whether the criteria for a metastasis were met on the additional sections. ITCs were detected in 59 (1.7%) of 3454 lymph nodes and in 41 (32.5%) of 126 patients. In 29 (49.2%) lymph nodes with ITCs on the primary slide, further sections resulted in a changed status from ITCs to a metastasis. In 7 (17.1%) of 41 patients, the pN category was changed. In patients with adenocarcinoma of the EGJ, the presence of ITCs in regional lymph nodes is a common observation. ITCs often represent part of a real metastasis. To obtain a pN category as accurate as possible, we strongly recommend thorough examination of regional lymph nodes with additional sections when ITCs are observed.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms

Esophageal cancer is a common human malignant tumor with high mortality. Glandular epithelial markers, such as CAM5.2, can be expressed in esophageal squamous cell carcinoma (ESCC), but the clinical significance of these cells in ESCC remains elusive.Immunohistochemical analysis of CAM5.2 was performed on 604 ESCC specimens using tissue microarray. Our study design and study population used retrospective cohorts based on the hospital information system and pathological information management system which included medical information, date of admission, procedures undergone, registration, examinations, and medication.In total, positive staining of CAM5.2 was 145 of 604 (24%). Statistical analysis showed that the expression of CAM5.2 had no relationship with sex, age, tumor differentiation, tumor size, tumor-node-metastasis (TNM) classification, and lymph node metastasis, but it was significantly associated with poor prognosis of overall survival (P = .0041) and disease-free survival (P = .0048) in ESCC patients.Herein, we report for the first time that the high expression of the CAM 5.2 is an independent predictor of poor prognosis in patients with ESCC.

Topics: Adult; Aged; Biomarkers; Biopsy; China; Cohort Studies; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prognosis; Retrospective Studies; Transcriptome

Circulating tumor cells (CTCs) are putative markers of tumor prognosis and may serve to evaluate patient's response to chemotherapy. CTCs are often detected as single cells but infrequently as clusters and are indicative of worse prognosis. In this study, we developed a short-term culture of nucleated blood cells which was applied to blood samples from breast, lung, esophageal and bladder cancer patients. Clusters of different degrees of compactness, classified as very tight, tight and loose were observed across various cancer types. These clusters show variable expression of cytokeratins. Cluster formation from blood samples obtained during the course of chemotherapy was found to be associated with disease progression and shorter overall survival. The short-term cultures offer a robust and highly reliable method for early prediction of treatment response in different cancer types.

Topics: Antineoplastic Agents; Breast Neoplasms; Disease Progression; Esophageal Neoplasms; Female; Humans; Kaplan-Meier Estimate; Keratins; Lung Neoplasms; Neoplastic Cells, Circulating; Prognosis; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Circulating tumor cells (CTCs) are tumor cells present in the bloodstream, which originate from tumor sites, and are ultimately responsible for metastasis or relapse in several types of cancer. However, to the best of our knowledge, only a few studies have investigated these extremely rare cells in esophageal squamous cell carcinoma (ESCC). In the present study, 63 patients with ESCC and 50 healthy donors were recruited, and the potential clinical significance of CTCs was assessed using subtraction enrichment and immunostaining‑fluorescence in situ hybridization. Blood samples were collected at the following times: At first diagnosis, following neoadjuvant chemoradiotherapy, 24 h and 13 days post‑surgery, and every 3 months during follow‑up. Cytokeratin (CK)‑positive and clustered CTCs only accounted for 1% of total CTCs detected, whereas most CTCs were CK‑negative aneuploid cells. Patients with ESCC (n=63) had higher CTC counts compared with healthy donors (control group; n=50) (area under curve=0.807, median CTC count, 2 vs. 0). However, there was no statistical association between CTC counts and sex, age, pathological stage, tumor location, tumor depth or lymph node involvement (P>0.05). The association of tumor development with CTC status and other circulating biomarkers was monitored in patients for a further 2 years. The results revealed that a change in CTC counts between first diagnosis and 13 days post‑surgery (ΔCTC) of ≥2/7.5 ml peripheral blood could be applied for predicting progression‑free survival (hazard ratio, 3.922; 95% confidence interval, 0.907‑16.951; P<0.05) in patients with ESCC. In conclusion, ΔCTC evaluation may be a promising indicator for predicting tumor prognosis and the clinical efficacy of treatment in patients with ESCC.

Topics: Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Cell Count; Chemoradiotherapy, Adjuvant; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Progression-Free Survival

The accumulated evidence has indicated the diagnostic role of cytokeratin (CK) and vimentin protein immunoassay in primary esophageal spindle cell carcinoma (PESC), which is a rare malignant tumor with epithelial and spindle components. However, it is largely unknown for the expression of CK and vimentin in pathological changes and prognosis of PESC.. Eighty-two PESC patients were identified from the esophageal and gastric cardia cancer database established by Henan Key Laboratory for Esophageal Cancer Research of Zhengzhou University. We retrospectively evaluated CK and vimentin protein expressions in PESC. Clinicopathological features were examined by means of univariate and multivariate survival analyses. Furthermore, the co-expression value of cytokeratin and vimentin was analyzed by receiver operating characteristic (ROC) curve.. The positive pan-cytokeratins AE1/AE3 (AE1/AE3 for short) staining was chiefly observed in cytoplasm of epithelial component tumor cells, with a positive detection rate of 85.4% (70/82). Interestingly, 19 cases showed AE1/AE3 positive staining both in epithelial and spindle components (23.2%). However, AE1/AE3 expression was not observed with any significant association with age, gender, tumor location, gross appearance, lymph node metastasis and TNM stage. Furthermore, AE1/AE3 protein expression does not show any effect on survival. Similar results were observed for vimentin immunoassay. However, in comparison with a single protein, the predictive power of AE1/AE3 and vimentin proteins signature was increased apparently than with single signature [0.75 (95% CI = 0.68-0.82) with single protein v.s. 0.89 (95% CI = 0.85-0.94) with AE1/AE3 and vimentin proteins]. The 1-, 3-, 5- and 7-year survival rates for PESC patients in this study were 79.3%, 46.3%, 28.0% and 15.9%, respectively. Multivariate analysis demonstrated age and TNM stage were independent prognostic factors for overall survival (P = 0.036 and 0.003, respectively). It is noteworthy that only 17.1% patients had a PESC accurate diagnosis by biopsy pathology before surgery (14/82). 72.4% PESC patients with biopsy pathology before surgery had been diagnosed as squamous cell carcinoma.. The present study demonstrates that cytokeratin and vimentin protein immunoassay is a useful biomarker for PESC accurate diagnosis, but not prognosis. The co-expression of cytokeratin and vimentin in both epithelial and spindle components suggest the possibility of single clone origination for PESC.

Topics: Adult; Aged; Anion Exchange Protein 1, Erythrocyte; Biomarkers, Tumor; Chloride-Bicarbonate Antiporters; Esophageal Neoplasms; Female; Gene Expression; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; ROC Curve; Sarcoma; Vimentin

To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy.. End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10 (n = 6), 17 (n = 8), 24 (n = 9), 31 (n = 6), 38 (n = 6), and 40 (n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation was completed to determine respective rates of carcinogenic development. Quantitative reverse transcription-polymerase chain reaction was performed to determine gene expression levels of. The overall study mortality was 15%. Causes of mortality included anastomotic leak, gastrointestinal hemorrhage, stomach ulcer perforation, respiratory infection secondary to aspiration, and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery, 100% of animals presented with esophagitis. Barrett's esophagus (BE) was first observed at 10 wk, and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk, and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition, two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine, respectively.. Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden, which may facilitate broader adoption to study EAC development, progression, and therapeutics.

Topics: Adenocarcinoma; Anastomosis, Surgical; Animals; Barrett Esophagus; Biomarkers, Tumor; Carcinogenesis; Disease Models, Animal; Disease Progression; Esophageal Neoplasms; Esophagus; Gastroesophageal Reflux; Humans; Jejunum; Keratin-19; Keratins; Male; Mucin-2; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Cross-contamination during or early after establishment of a new cell line could result in the worldwide spread of a misidentified cell line. Therefore, newly established cell lines need to be authenticated by a reference standard method. This study was conducted to investigate the authenticity of a newly established epithelial cell line of human esophageal squamous cell carcinoma (ESCC) called YM-1 using short tandem repeat (STR) DNA profiling method. Primary human ESCC epithelial cells were cultured from the fresh tumor tissue of an adult female patient. Growth characteristics and epithelial originality of YM-1 cells were studied. Genomic DNA was isolated from YM-1 cells harvested at passage 22 and ESCC donor tumor sample on two different days to prevent probable DNA contamination. STR profiling was performed using AmpFℓSTR® Identifiler® Plus PCR Amplification Kit. To address whether YM-1 cells undergo genetic alteration as the passage number increases, STR profiling was performed again on harvested cells at passage 51. YM-1 cells grew as a monolayer with a population doubling time of 40.66 h. Epithelial originality of YM-1 cells was confirmed using ICC/IF staining of cytokeratins AE1/AE3. The STR profile of the ESCC donor tumor sample was the same with YM-1 cells at passage 22. However, STR profile of the donor tumor sample showed an off-ladder (OL) allele in their D7S820 locus. Also, re-profiling of YM-1 cells at passage 51 showed a loss of heterozygosity (LOH) at D18S51 locus. This suggests that long-term culture of cell lines may alter their DNA profile. Comparison of the DNA fingerprinting results in DSMZ, and ATCC STR profiling databases confirmed unique identity of YM-1 cell line. This study provides an easy, fast, and reliable procedure for authentication of newly established cell lines, which helps in preventing the spread of misidentified cells and improving the reproducibility and validity of experiments, consequently.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; DNA Fingerprinting; DNA, Neoplasm; Esophageal Neoplasms; Female; Humans; Keratins; Loss of Heterozygosity; Microsatellite Repeats; Middle Aged; Reference Standards; Reproducibility of Results; Time Factors; Tumor Cells, Cultured

Tumor budding has prognostic significance in many carcinomas and is defined as the presence of detached isolated single cells or small cell clusters up to 5 cells at the invasion front (peritumoral budding [PTB]) or within the tumor (intratumoral budding [ITB]). For esophageal adenocarcinomas (EACs), there are currently only few data about the impact of this morphological feature. We investigated tumor budding in a large collective of 200 primarily resected EACs. Pancytokeratin staining was demonstrated to be superior to hematoxylin and eosin staining for the detection of buds with substantial to excellent interobserver agreement and used for subsequent analysis. PTB and ITB were scored across 10 high-power fields (HPFs). The median count of tumor buds was 130/10 HPFs for PTB (range, 2-593) and 80/10 HPFs for ITB (range, 1-656). PTB and ITB correlated significantly with each other (r = 0.9; P < .001). High PTB and ITB rates were seen in more advanced tumor categories (P < .001 each); tumors with lymph node metastases (P < .001/P = .002); and lymphatic, vascular, and perineural invasion and higher tumor grading (P < .001 each). Survival analysis showed an association with worse survival for high-grade ITB (P = .029) but not PTB (P = .385). However, in multivariate analysis, lymph node and resection status, but not ITB, were independent prognostic parameters. In conclusion, PTB and ITB can be observed in EAC to various degrees. High-grade budding is associated with aggressive tumor phenotype. Assessment of tumor budding, especially ITB, may provide additional prognostic information about tumor behavior and may be useful in specific cases for risk stratification of EAC patients.

Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; Chi-Square Distribution; Coloring Agents; Eosine Yellowish-(YS); Esophageal Neoplasms; Germany; Hematoxylin; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Logistic Models; Lymphatic Metastasis; Multivariate Analysis; Neoplasm Grading; Neoplasm Invasiveness; Observer Variation; Odds Ratio; Phenotype; Predictive Value of Tests; Proportional Hazards Models; Reproducibility of Results; Staining and Labeling; Switzerland

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis due to its highly invasive and metastatic potential. The molecular pathogenesis underlying the invasive mechanism of ESCC is not well known because of the lack of existing models to study this disease. p120-Catenin (p120ctn) and the epidermal growth factor receptor (EGFR) have each been implicated in several cancers, including ESCC. p120ctn is down-regulated in 60% of ESCC tumors, whereas EGFR is the most commonly overexpressed oncogene in ESCC. For these reasons, we investigated the cooperation between p120ctn and EGFR and its effect on ESCC invasion. We show that p120ctn down-regulation is commonly associated with EGFR overexpression. By using a three-dimensional culture system, we demonstrate that the inverse relationship between p120ctn and EGFR has biological implications. Specifically, p120ctn down-regulation coupled with EGFR overexpression in human esophageal keratinocytes (EPC1-PE) was required to promote invasion. Morphological comparison of EPC1-PE cells grown in three-dimensional culture and human ESCC revealed identical features, including significantly increased cellularity, nuclear grade, and proliferation. Molecular characteristics were measured by keratin expression patterns, which were nearly identical between EPC1-PE cells in three-dimensional culture and ESCC samples. Altogether, our analyses have demonstrated that p120ctn down-regulation and EGFR overexpression are able to mimic human ESCC in a relevant three-dimensional culture model.

Topics: Antigens, CD; Cadherins; Carcinoma, Squamous Cell; Catenins; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Delta Catenin; Down-Regulation; Epithelium; ErbB Receptors; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness

Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Anemia; Barrett Esophagus; Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Comorbidity; Deglutition Disorders; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Follow-Up Studies; Gastroesophageal Reflux; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Second Primary; Prognosis; Smoking; Survival Rate; Transcription Factors; Treatment Outcome

To characterize the immunophenotypic relationship between the squamous and the glandular compartments in the oesophagus of patients with columnar-lined oesophagus (CLO).. Eight tissue blocks from three oesophageal resection specimens from patients who underwent oesophagectomy for adenocarcinoma of the oesophagus were selected for immunohistochemical analysis. The markers of intestinal differentiation [CK20, CDX2 and MUC2] were all expressed in the expected pattern, solely in the glandular compartment of the resection specimens. CK4, CK17 and lysozyme were expressed in both the glandular and the squamous compartments. In addition, CK17 expression was found on both the squamous and glandular margins of the squamocolumnar transformation zones and in the submucosal gland (SMG) intraglandular and excretory ducts.. There is an immunophenotypic relationship between the squamous and the glandular compartments of the CLO, with expression of lysozyme, CK4 and CK17 in both squamous and columnar cells. These overlapping immunophenotypes indicate similar differentiation paths, and link the SMG unit with the columnar metaplasia and the neosquamous islands in CLO. Our findings support the theory of a cellular origin of CLO and neosquamous islands from the SMG unit.

Topics: Adenocarcinoma; CDX2 Transcription Factor; Esophageal Neoplasms; Esophagus; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Metaplasia; Mucin-2; Mucous Membrane

Hsp90α (heat shock protein 90α), one of the important molecular chaperones in cancer cell signal transduction, has been a new candidate target for cancer therapy. Cyclin B1, the client protein of Hsp90α, plays a key role as a mitotic cyclin in the G2-M phase transition during the cell cycle progression. However, the relationship between the level of HSP90α and cyclin B1, the location of Hsp90α and cyclin B1 in prognosis of esophageal squamous cell carcinoma (ESCC) has not been examined. Here, we demonstrate that the diagnostic significance of Hsp90α and cyclin B1 by immunohistochemistry and the association of Hsp90α and cyclin B1 expression in ESCC. In the specimens from 105 ESCC patients (81 stained with Hsp90α antibody by Immunohistochemistry, 65 with cyclin B1 antibody, and among them, 41 paired specimens were stained with Hsp90α and cyclin B1 respectively, and then checked for the correlation of the level and location of Hsp90α and cylcin B1. The positivity rate of Hsp90α and cyclin B1 expression were 96.3% (78 of 81) and 84.6% (55 of 65) respectively. Both of them, the expression levels are associated with the clinical pathological stage (Hsp90α, p=0.027; cyclin B1, p=0.007). No association was found between Hsp90α or cyclin B1 and gender, age, tumor location. As to TMN stage, there is no association with the level of Hsp90α, However, cyclin B1 expression is significantly related to tumor status (p=0.002). Interestingly, Hsp90α expression was negatively correlated to cyclin B1 expression (Gamma=-0.692, p=0.007) in the keratin pearls though there is a positive correlation in the other areas of tumor (Gamma=0.503, p=0.015), which suggest Hsp90α might play diverse roles in the cyclin B1 expression and cyclin B1 related cell cycle regulation in the different area of tumor. These findings demonstrated that the expression of Hsp90α, cyclin B1 protein is associated with tumor malignancy and prognosis for patients with human esophageal squamous cell carcinoma, and Hsp90α might be involved in cyclin B1 expression regulation and cell cycle regulation in keratin peal formation of ESCC.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin B1; Cytoplasmic Structures; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; HSP90 Heat-Shock Proteins; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate

To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions.. In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pink-color sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed.. A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range: 2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous layer and cellular atypia were significantly associated with the pink-color sign. After Bonferroni correction, there were no significant associations between the pink-color sign and presence of the basal membrane or vascular change. Multivariate analyses found that only absence of the keratinous layer was independently associated with the pink-color sign (OR = 58.8, 95%CI: 5.5-632). Quantitative analysis was performed on 10 superficial esophageal neoplasms with both pink-color sign positive and negative areas in 10 patients. Pink-color sign positive mucosa had a lower mean color value in the late phase (pinkish color) than in the early phase (yellowish color), and had similar mean color values in the late and final phases. These findings suggest that pink-color positive mucosa underwent color fading from the color of the iodine (yellow) to the color of the mucosa (pink) within 2-3 min after iodine staining. Pink-color sign negative mucosa had similar mean color values in the late and early phases (yellowish color), and had a lower mean color value in the final phase (pinkish color) than in the late phase. These findings suggest that pink-color sign negative mucosa did not undergo color fading during the 2-3 min after iodine staining, and underwent color fading only after spraying of sodium thiosulfate.. The pink-color sign was associated with absence of the keratinous layer. This sign may be caused by early fading of iodine staining.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cell Nucleus; Color; Cytoplasm; Duodenoscopy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Female; Humans; Iodine; Keratins; Male; Middle Aged; Mitosis; Mucous Membrane; Staining and Labeling; Time Factors

When adenocarcinomas arise within the esophagus, particularly when located away from the gastroesophageal junction, it may be important in some patients to differentiate between a primary esophageal adenocarcinoma and metastasis from another site. Lung adenocarcinoma is one tumor that has been reported to frequently metastasize to the esophagus.. To create a panel of immunohistochemical markers that can reliably distinguish between an esophageal and pulmonary primary; within the gastrointestinal pathology literature, including published articles and textbooks, common lung immunohistochemical markers, such as TTF-1, are assumed to be negative in esophageal adenocarcinoma, yet, to our knowledge, no study has yet investigated the veracity of that presumption.. In this study, 24 cases each of pulmonary and esophageal adenocarcinomas were stained with TTF-1, napsin A, CDX2, 34βE12, N-cadherin, and IMP3 in an attempt to define an optimal panel for differentiation. Esophageal adenocarcinomas occurring at the gastroesophageal junction were excluded in this study because a gastric primary tumor cannot be excluded in those cases.. Surprisingly, TTF-1 and napsin A were positive in similar proportions of tumors from both sites. Those markers that differentiated statistically between esophageal and pulmonary adenocarcinoma were IMP3, CDX2, and N-cadherin.. When differentiating the origin of a tumor as either esophageal or pulmonary, an immunohistochemical panel consisting of IMP3, CDX2, and N-cadherin is superior to either TTF-1 or napsin A.

Topics: Adenocarcinoma; Antigens, CD; Aspartic Acid Endopeptidases; Biomarkers, Tumor; Cadherins; CDX2 Transcription Factor; Diagnosis, Differential; Esophageal Neoplasms; Homeodomain Proteins; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Nuclear Proteins; RNA-Binding Proteins; Staining and Labeling; Thyroid Nuclear Factor 1; Transcription Factors

The expression of the activated leukocyte cell adhesion molecule (ALCAM and CD166) is increased in various types of cancer. We aimed to evaluate its role as a prognostic marker for esophageal cancer (EC). We retrospectively analyzed ALCAM expression in 299 primary lesions, 147 lymph node and 46 distant metastases from EC patients, on a tissue microarray using immunohistochemistry. Bone marrow samples from representative cancer patients (n = 16), taken before primary surgery, were stained by double-immunofluorescence for ALCAM and cytokeratins (CK). Blood serum samples from 236 cancer patients and 127 controls were analyzed for serum ALCAM (s-ALCAM) by ELISA. The immunohistochemical analysis showed increased ALCAM expression in the majority of lesions (primary tumor 71%, lymph node 76% and distant metastases 80%). ALCAM expression was not associated with histopathological parameters except for tumor grading (p = 0.015). ALCAM-positive patients had significantly worse recurrence-free and overall survival (OS; p = 0.002). Disseminated tumor cells (DTC) in bone marrow showed two phenotypes, ALCAM+/CK+ (36%) and ALCAM-/CK+ (64%). Multivariate analysis revealed that ALCAM expression and elevated s-ALCAM serum values are powerful prognostic variables for OS in patients with EC (hazard ratio [HR] 3.987, 95% confidence interval [95%CI] 1.906-8.340, p < 0.001 and HR 1.915, 95%CI 1.021-3.592, p = 0.043). The results of our study provide preliminary evidence for the potential clinical utility of ALCAM as a prognostic biomarker for EC, which might be a basis for future clinical application. In addition, ALCAM expression in a subset of DTC of the bone marrow indicates a potential function in the metastatic cascade of EC.

Topics: Activated-Leukocyte Cell Adhesion Molecule; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Grading; Prognosis; Protein Array Analysis; Retrospective Studies

Distinguishing adenocarcinoma and squamous cell carcinoma of the esophagus is often based on morphological criteria and can be difficult in small biopsies. We analyzed commonly used immunohistochemical markers (p63, cytokeratin 5/6, cytokeratin 7, CDX2, MUC2, and MUC5AC) and 2 new markers, anterior gradient homolog 2 and SOX2, in esophageal carcinomas to establish the best panel to distinguish these tumors. Tissue microarrays with 69 esophageal adenocarcinomas and 41 whole sections of esophageal squamous cell carcinomas were stained for these markers and semiquantitatively scored. Sensitivities and specificities were calculated for individual markers and select combinations using the morphological diagnosis as a gold standard. All squamous cell carcinomas expressed p63 with 38 of 41 demonstrating reactivity in more than 75% of tumor cells. Cytokeratin 5/6 expression was seen in 40 of 41 squamous cell carcinomas with 39 of 41 demonstrating reactivity in more than 75% of tumor cells. SOX2 expression was present in 35 of 41 of squamous cell carcinomas but also in 24 of 69 of adenocarcinomas, frequently demonstrating extensive reactivity in adenocarcinomas. Anterior gradient homolog 2 was highly sensitive for adenocarcinoma and present in 68 of 69 of cases, but anterior gradient homolog 2 reactivity was also identified in 15 of 41 of squamous cell carcinomas, typically demonstrating focal reactivity in squamous cell carcinoma. MUC5AC expression was seen almost exclusively in adenocarcinomas with only a single squamous cell carcinoma demonstrating focal MUC5AC staining. Overall, the dual expression of both p63 and cytokeratin 5/6 was 99% specific and 98% sensitive for squamous cell carcinoma. In addition, anterior gradient homolog 2 and MUC5AC are useful positive markers of adenocarcinoma in the setting of absent or diminished p63 and cytokeratin 5/6 staining.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Esophageal Neoplasms; Esophagogastric Junction; Humans; Keratins; Mucin 5AC; Mucoproteins; Oncogene Proteins; Proteins; Sensitivity and Specificity; Tissue Array Analysis; Transcription Factors; Tumor Suppressor Proteins

To analyze the clinicopathological characteristics and prognosis of a rare histological type of esophageal cancer-sarcomatoid carcinoma.. Clinicopathological data of 31 patients with esophageal sarcomatoid carcinoma who underwent surgery in the Department of Thoracic Surgery of Zhejiang Cancer Hospital from Jan 2000 to Dec 2009 were collected and analyzed. The survival analysis was performed using Kaplan-Meier method.. All the patients underwent surgery. Of the 31 patients, one received preoperative chemoradiotherapy and postoperative chemotherapy, and 8 received postoperative chemotherapy. All the tumors were located in the middle or lower esophagus. Microscopically, the tumors were composed of both carcinomatous and sarcomatous components, and there was a transition between the two components, but no obvious heterogenous elements such as osteosarcoma, chondrosarcoma or rhabdomyosarcoma were found. In the carcinomatous components, positive expression of CK and EMA was found in all the 31 cases, and positive expression of vimentin in 5 of the 31 cases. In the sarcomatous components, positive expression of CK, EMA and vimentin was found in 29, 28 and 23 cases, respectively. The 1-, 3-, and 5-year survival rates were 80.6%, 55.9% and 33.4%, respectively, and the median survival time was 40 months.. Esophageal sarcomatoid carcinoma is a particular type of esophageal malignancy with unique clinicopathological features. The diversity and complexity of the carcinomatous and sarcomatous components and their potential of transformation and differentiation lead to different prognosis from each other.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinosarcoma; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Mucin-1; Prognosis; Survival Rate; Vimentin

Esophageal squamous cell carcinoma (ESCC) is considered one of the most aggressive cancers with poor prognosis. The high molecular weight cytokeratin 34βE12 (CK34βE12) is recognized by the antibody, that is expressed in the cytoplasm of epithelial basal cells, and has been considered as a potential marker for prostate cancer, breast cancer, and basaloid carcinoma of the lung. However, there are no clinicopathological studies investigating CK34βE12 expression at the invasive front of ESCC. In this study, we examined 170 surgically resected cases of ESCC to clarify the clinicopathological significance of CK34βE12 expression. CK34βE12 expression was found in 85.3% (145/170) of ESCC cases and was significantly correlated with lymph node metastasis (66.2% [96/145], P = 0.034), depth of tumor invasion (57.9% [84/145], P = 0.042), and differentiation (82.1% [119/145], P = 0.013). These results indicated that CK34βE12 expression is a good indicator of lymph node metastasis, depth of tumor invasion, and differentiation in case of ESCC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Disease Progression; Esophageal Neoplasms; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis

Involved lymph nodes (LN) are a negative prognostic factor in esophageal cancers. To assess the role of nodal micrometastases, we performed immunohistochemical analyses of LN after resection of node-negative esophageal cancers and correlated the results with survival.. Seventy patients with esophageal cancer after curative resection and conventionally negative nodes were included. The LN were examined with six consecutive sections (three hematoxylin and eosin (HE) stained and three stained immunohistochemically with the cytokeratin (CK) antibodies AE1/AE3). Survival was evaluated uni- and multivariately. Median follow-up was 4.1 years.. Immunohistochemical analysis showed CK-positive LN in 16 (23%) patients. Of those 16 cases with CK-positive LN, nine had aviable macrometastases, ten had CK-positive scars/fibrosis and five had viable micrometastases. All patients with aviable macrometastases or CK-positive scars/fibrosis had undergone neoadjuvant chemoradiation. Five-year survival was 48% in all patients. In univariate analysis, survival was worse in patients with CK-positive LN (5-year survival of 30% vs. 54% in CK-negative LN; p < 0.02) and in patients with squamous cell carcinoma (5-year survival of 38% vs. 75% in adenocarcinoma; p = 0.05). Multivariate analysis revealed CK-positive LN (p = 0.02) and (borderline) squamous cell carcinoma (p = 0.06) as negative prognostic factors.. The immunohistochemical analysis of LN may detect (viable or non-viable) tumor cells in lymph nodes after resection of conventionally node-negative esophageal cancers. Conventional pathological analysis by HE, therefore, understages esophageal cancer in these cases. The detection of CK-positive cells in resected LN is an independent prognostic factor in otherwise LN-negative esophageal cancer.

Topics: Adult; Aged; Biomarkers, Tumor; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Postoperative Period; Retrospective Studies; Thorax

We report the malignant characteristics of circulating tumor cells (CTCs) and the corresponding molecular features of the primary tumor in a patient with esophageal squamous cell carcinoma (ESCC). A 70-year-old male patient was diagnosed with TNM stage T3N0M0 ESCC. Before surgery, seven intact CTCs and 12 CTCs with a fragmented membrane were detected in 7.5 mL of peripheral blood by immunofluorescence staining. One week after radical resection of the primary tumor, four CTCs were identified in 7.5ml peripheral blood. All CTCs were confirmed as having a malignant phenotype by chromosomal analysis and routine cell staining. Ninety percent of the CTCs were found to have polysomic chromosomes 8 and 20 by fluorescence in situ hybridization (FISH). Immunofluorescence analysis showed that all of the primary tumor cells detected were cytokeratin8/18/19 (CK8/18/19)-positive, but only 1% were CD133-positive. The serum CA19-9 and CEA level were normal in the process of diseases. The patient died 6 months after surgery as a result of lung metastases and other complications. The results of this study suggest that the dynamics and malignant characteristics of both CTCs and the corresponding primary tumor during the disease process may predict tumor burden and the risk of relapse and metastasis.

Topics: AC133 Antigen; Aged; Antigens, CD; Carcinoma, Squamous Cell; Chromosome Aberrations; Chromosomes, Human, Pair 20; Chromosomes, Human, Pair 8; Esophageal Neoplasms; Fatal Outcome; Glycoproteins; Humans; Keratins; Male; Neoplastic Cells, Circulating; Peptides

Behaviors of esophageal cancer are different according to the geographic distribution. The prevalence of bone marrow involvement in patients with esophageal cancer has been shown to be between 40% and 90%, but clinical correlation is unknown. The aim of this study is to determine the rate of bone marrow involvement in patients with esophageal cancer in the northeast of Iran and its relationship with clinicopathologic findings of the tumors.. A total of 43 patients with esophageal cancer, who were candidates for esophagectomy (without neo-adjuvant chemotherapy), were enrolled in this study from 2007 to 2009. Bone marrow samples derived from rib bone were stained with hematoxylin and eosin (H&E) to distinguish tumoral cells, and cytokeratin immunohistochemistry (CKIHC) was used to determine micrometastasis. The correlation of the results was studied with the histopathologic indices of primary tumor (T (tumor), N (node) and length of tumoral involvement and grading) as well as characteristics of the patients (sex and age).. The mean age was 64 (57-70) years and the M/F ratio was 2.9. As many as 38 patients (88.4%) had squamous cell carcinoma and five patients (11.6%) had adenocarcinoma. In nine cases (20.9%), the H&E test, and, in 13 cases (30.2%), the CKIHC evaluation was positive. Statistically, there was no relationship between the pathologic type and the stage of T with the H&E study and CKIHC test, respectively. On the other hand, a significant meaningful correlation was found between microscopic bone marrow involvement as well as mediastinal lymph node involvement and grade of the tumor.. Bone marrow involvement incidence was low in our geographic area. According to our study, bone marrow involvement in esophageal cancer is related to differentiation grade and mediastinal lymph node involvement.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Cross-Sectional Studies; Esophageal Neoplasms; Esophagectomy; Female; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Neoplasm Micrometastasis; Neoplasm Proteins; Neoplasm Staging

Primary esophageal small cell carcinoma (PESCC) is a relatively rare and aggressive tumor with poor prognosis. Systemic spreading and metastasis often occur at diagnosis. Although 5-year survival rate of superficial squamous cell carcinoma of the esophagus can be 86.1%, 5-year survival rate of superficial PESCC is still relatively low. This study mainly retrospectively analyzed clinicopathological and immunohistochemical features of 15 cases of superficial PESCC in our hospital from 1990 to 2004, in order to find suitable diagnostic markers and applicable therapies for this disease. The records mainly included presenting symptoms, demographics, diagnostic method, histopathology, follow-up, and therapy. Immunohistochemical staining of chromogranin A (CgA), neuron-specific enolase (NSE), synaptophysin (Syn), neuronal cell adhesion molecules (CD56), thyroid transcription factor-1 (TTF-1), cytokeration 34betaE12 (CK34betaE12), cytokeratin (AE1/AE3), and cytokeratin 10/13 was performed. Incidence of superficial PESCC accounted for 4.8% of that of superficial carcinoma of the esophagus during the same period. Initial symptoms of all patients were dysphagia or accompanied with retrosternal pain and upper abdominal pain, and duration of these symptoms was 75 days averagely. Mean age of patients was 58.8 years old, and the male-to-female ratio was 2.75 : 1. Lesions were mainly located at middle thoracic esophagus. One, 2, and 5-year survival rates were 66.7, 33.3, and 6.7%, respectively. The median survival time was 19 months and mean survival time was 23.7 months after diagnosis. The percentages of PESCC samples with positive immunoreactivity were NSE 100%, Syn 100%, AE1/AE3 100%, CD56 93.3%, TTF-1 60%, CgA 53.3%, CK34betaE12 6.7%, and cytokeratin 10/13 0%, respectively. Our study suggested that PESCC was a rare and aggressive tumor with high malignancy. Superficial PESCC had rapid progression and poor prognosis compared with superficial squamous cell carcinoma of the esophagus at the same stage. The systemic therapy based on combination of postoperative chemotherapy and radiotherapy might be an effective approach for the treatment of superficial PESCC as a systemic disease. Higher proportion of positive labeling of NSE, Syn, AE1/AE3, CD56, TTF-1, and CgA in PESCC was valuably applied in diagnosis and differential diagnosis.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Small Cell; CD56 Antigen; Chromogranin A; Deglutition Disorders; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Humans; Keratin-13; Keratins; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Nuclear Proteins; Phosphopyruvate Hydratase; Retrospective Studies; Sex Factors; Survival Rate; Synaptophysin; Thyroid Nuclear Factor 1; Transcription Factors; Treatment Outcome

The molecular mechanism underlying epithelial metaplasia in Barrett's esophagus remains unknown. Recognizing that Hedgehog signaling is required for early esophageal development, we sought to determine if the Hedgehog pathway is reactivated in Barrett's esophagus, and if genes downstream of the pathway could promote columnar differentiation of esophageal epithelium.. Immunohistochemistry, immunofluorescence, and quantitative real-time polymerase chain reaction were used to analyze clinical specimens, human esophageal cell lines, and mouse esophagi. Human esophageal squamous epithelial (HET-1A) and adenocarcinoma (OE33) cells were subjected to acid treatment and used in transfection experiments. Swiss Webster mice were used in a surgical model of bile reflux injury. An in vivo transplant culture system was created using esophageal epithelium from Sonic hedgehog transgenic mice.. Marked up-regulation of Hedgehog ligand expression, which can be induced by acid or bile exposure, occurs frequently in Barrett's epithelium and is associated with stromal expression of the Hedgehog target genes PTCH1 and BMP4. BMP4 signaling induces expression of SOX9, an intestinal crypt transcription factor, which is highly expressed in Barrett's epithelium. We further show that expression of Deleted in Malignant Brain Tumors 1, the human homologue of the columnar cell factor Hensin, occurs in Barrett's epithelium and is induced by SOX9. Finally, transgenic expression of Sonic hedgehog in mouse esophageal epithelium induces expression of stromal Bmp4, epithelial Sox9, and columnar cytokeratins.. Epithelial Hedgehog ligand expression may contribute to the initiation of Barrett's esophagus through induction of stromal BMP4, which triggers reprogramming of esophageal epithelium in favor of a columnar phenotype.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Bile; Bile Reflux; Bone Morphogenetic Protein 4; Calcium-Binding Proteins; Cell Communication; Cell Differentiation; Cell Line; Disease Models, Animal; DNA-Binding Proteins; Epithelial Cells; Esophageal Neoplasms; Esophagus; Gastroesophageal Reflux; Hedgehog Proteins; Humans; Hydrogen-Ion Concentration; Keratins; Mesoderm; Metaplasia; Mice; Mice, Transgenic; Patched Receptors; Patched-1 Receptor; Phenotype; Precancerous Conditions; Receptors, Cell Surface; RNA Interference; Signal Transduction; SOX9 Transcription Factor; Transfection; Tumor Suppressor Proteins

Deciphering the molecular basis of esophageal cancer metastasis requires adequate experimental models. Epithelial-mesenchymal transition (EMT) is the hallmark of tumor metastasis. As a promoter of the malignant progression of esophageal cancer, epidermal growth factor (EGF) has been shown to induce EMT in several cell lines. In this study we examined the effects of EGF on esophageal carcinoma EC109 cells. We found that EGF at high concentration induced the cells to undergo morphological change, exhibit higher invasive and metastatic potential, as well as change in the expression of lineage markers. This EMT model might facilitate mechanistic studies of esophageal cancer metastasis.

Topics: Cell Dedifferentiation; Cell Differentiation; Cell Division; Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Epidermal Growth Factor; Epithelial Cells; Esophageal Neoplasms; Gelatin; Humans; Keratins; Mesoderm; Neoplasm Invasiveness; Neoplasm Metastasis; Recombinant Proteins; Vimentin; Wound Healing

Both endoscopic and surgical treatments are recommended for m3- or sm1-adenocarcinomas of the esophagus, depending on patients' lymph nodal status. Lymphatic dissemination is related to tumor infiltration depth, but varying incidences have been reported in m3- and sm1-adenocarcinomas. The study aim was to investigate whether the presence of occult tumor cells in lymph nodes could explain this variation.. Sixty-three node-negative (N0) patients with early esophageal adenocarcinoma (m2/m3/sm1-tumors) were included. Multilevel-sectioning of lymph nodes was performed; sections were stained by means of immunohistochemistry with cytokeratin marker CAM5.2. Two pathologists searched for micrometastases (0.2-2.0  mm) and isolated tumor cells (ITCs, <0.2  mm).. Positive CAM5.2 staining in lymph nodes was not seen in any of the 18 m2-patients. In 2/25 m3-tumors (8.0%) an ITC was found, but no micrometastases. Tumor cells were identified in 4/20 sm1-tumors (20.0%): three micrometastases and one ITC. Median follow-up was 121 months. Two m3-patients (3.2%) died due to disease recurrence, including one patient in whom an ITC was detected.. Lymphatic migration of tumor cells was found in node-negative m3- and sm1-adenocarcinomas of the esophagus (8.0% and 20.0%, respectively). However, the clinical relevance of these occult tumor cells should become apparent from large series of endoscopically treated patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate

To assess the role of immunohistochemically detectable nodal microinvolvement of patients with "curatively" resected esophageal carcinoma.. In 73 patients with resectable esophageal carcinoma [squamous cell carcinoma (SCC), n = 45 (61.6%); adenocarcinoma (AC), n = 28 (38.4%)] a total of 2174 lymph nodes (LN) were removed. In each of the 1958 LN classified as negative on conventional histopathology, immunohistochemistry was performed using the anticytokeratin antibody AE1/AE3. To determine the role of the amount of residual tumor load, the patients were grouped according to the percentage of LN affected with micrometastasis (0%, <11%, and > or =11%).. Tumor cells were immunohistochemically detected in 47 LN (2.4%) from 25 (34.2%) patients. Five-year overall survival probability (5-YSP) of 30% in pN(0 )patients with detected occult tumor cells in LN was significantly worse than that in those without nodal microinvolvement (76%, P = 0.021), hereby resembling that of pN1-patients (24%, P = 0.84). Median overall survival in patients with no (0%), low (<11%), and high (>11%) micrometastatic tumor load was 43, 27, and 11 months, respectively. Substratification according to histological type showed that, in patients with AC, the presence of nodal microinvolvement had a significant impact on 5-YSP (0% versus 65%; P = 0.03), whereas in patients with SCC, differences of 5-YSP were only of borderline significance (24% versus 53%; P = 0.081).. Minimal tumor cell load as assessed by the ratio of micrometastatically affected LN is a complementary tool for better risk stratification of patients with esophageal carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Disease Progression; Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate

Esophageal cancer is a frequently fatal malignancy, and is described in certain regions in Northeast India with an incidence of esophageal squamous cell carcinoma many fold higher than the rest of the population. The population in Northeast India is at higher risk due to poor nutritional status, consumption of fermented betel quid and other oral tobacco products besides smoking and alcohol intake. Cytokeratins (CKs) are the major constituents of the esophageal epithelium and may show gain or loss of CKs as the cancer progresses from normal epithelium to invasive phenotype. In this study, we studied the immunohistochemical expression of 5 CKs (CK4, CK5, CK8, CK14, and CK17) in the normal esophageal epithelium and esophageal squamous cell carcinoma from both the general population and the high-risk population of Assam in Northeast India. The CK expression profile was similar to other published data in general. Further analysis demonstrated differences in CK expression between the general and the high-risk tumor samples. CK5 and CK8 expression was altered in the high-risk population. The significance of these differences is unclear, but suggests a connection to the etiologic factors.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; India; Keratins; Risk Factors; Tissue Array Analysis

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinosarcoma; Esophageal Neoplasms; Esophagectomy; Histiocytoma, Malignant Fibrous; Humans; Keratins; Male; Middle Aged; Mucin-1; Vimentin

Topics: Adenocarcinoma; Animals; Computational Biology; Esophageal Neoplasms; Genomics; Genotype; Humans; Keratins; Mutation, Missense; Neoplasm Transplantation; Phenotype; Vimentin

AFP-producing tumors are uncommon. They have mostly been described of pulmonary origin. However, they have also been described from gastrointestinal tract. Esophageal involvement with hepatoid tumor has been rarely described. The diagnosis is clinically challenging in patients with metastatic disease to liver. We present an interesting case of AFP-producing esophageal tumor, describing its clinical presentation, endoscopic manifestation, as well as histological features.

Topics: alpha-Fetoproteins; Carcinoma, Hepatocellular; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged

The aim of this study was to examine the clinical usefulness of cytokeratin 19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in patients with esophageal cancer treated with radiation therapy.. Fifty-one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC antigen serum levels were measured at the start and the end of radiation therapy.. CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21-1 levels were significantly correlated with TNM stages, tumor depth and lymph node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no correlation was observed between SCC antigen and these factors. The values of CYFRA 21-1 in all patients who survived without recurrence were under the cutoff level at the end of treatment, but the values in all patients with locoregional recurrence were above the level. However, there was no significant correlation between SCC antigen level at the end of treatment and any clinical outcome.. The results suggest that the evaluation of CYFRA 21-1 would be useful not only for assessment before radiation therapy but also for monitoring after radiation therapy in the treatment for esophageal cancer.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Keratin-19; Keratins; Lymph Nodes; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Recurrence; Serpins; Time Factors; Treatment Outcome

Neoadjuvant chemotherapy (NACT) has been postulated but not yet proven to eradicate micrometastases and improve the prognosis of patients with advanced esophageal squamous cell carcinomas (ESCC). Cytokeratin immunohistochemistry of the lymph nodes of ESCC revealed immunohistochemical micrometastases (IHM) and cytokeratin deposits (CD), which are hyalinized denucleated particles considered to be cadavers of carcinoma cells. Successful chemotherapy should convert cancer cells from IHM to CD and improve the status of ESCC patients from systemic disease to regional disease.. Cytokeratin immunostaining of surgically removed lymph nodes was performed for 107 patients with node-positive ESCC, including 32 patients without preoperative treatment (Surgery group) and 75 patients undergoing NACT using CDDP, doxorubicin hydrochroride, and 5-fluorouracil (NACT group). Cytokeratin-positive staining was done for serial hematoxylin-eosin-stained sections and classified as pathologic metastasis, IHM, or CD.. CD was observed less frequently in the Surgery group than in the NACT group (6% vs 43%, P < .0001), whereas IHM was more frequent in the former (47% vs 24%, P = .019). IHM was a poor prognostic factor in both groups, whereas CD was a favorable one in the NACT group. The effect of chemotherapy on IHM was classified as eradicated, IHM(-)/CD(+); persistent, IHM(+)/CD(+); no effect, IHM(+)/CD(-); or not informative, IHM(-)/CD(-). This classification correlated well with the clinical response of the primary neoplasm, number of pathologic metastases, and postoperative survival (3-year survival rates: 78%, 18%, 0%, and 38%). IHM/CD was found to be an independent prognostic factor together with the number of pathologic metastases in the multivariate analysis.. Disappearance of IHM and the emergence of CD suggest the eradication of micrometastases by NACT. The clinical benefit of NACT was apparent for IHM(-)/CD(+) patients with node-positive ESCC.

Topics: Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Esophageal Neoplasms; Fluorouracil; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Prognosis

Investigation of canine dysphagia is performed by a combination of diagnostic imaging, direct visualisation of the upper gastrointestinal tract, and ancillary diagnostic testing to differentiate between structural and functional causes. Video fluoroscopy may be especially helpful. The case of a seven-year-old Border collie that presented with a history of progressive pharyngeal dysphagia is described. Fluoroscopic investigation was initially suggestive of functional pharyngeal disease, but magnetic resonance imaging and surgical exploration demonstrated the presence of a diffuse, scirrhous, poorly differentiated carcinoma with extensive oesophageal involvement. This case highlights that, in some circumstances, fluoroscopy may occasionally be of limited use in the investigation of dysphagia in the dog.

Topics: Adenocarcinoma, Scirrhous; Animals; Deglutition Disorders; Dog Diseases; Dogs; Esophageal Neoplasms; Esophagus; Fluoroscopy; Keratins; Magnetic Resonance Imaging; Male; Treatment Outcome

Upper aerodigestive tract (UADT) cancer, including oral and esophageal cancer, is an important cause of cancer deaths worldwide. Patients with UADT cancer are frequently zinc deficient (ZD) and show a loss of function of the pivotal tumor suppressor gene p53. The present study examined whether zinc deficiency in collaboration with p53 insufficiency (p53+/-) promotes lingual and esophageal tumorigenesis in mice exposed to low doses of the carcinogen 4-nitroquinoline 1-oxide. In wild-type mice, ZD significantly increased the incidence of lingual and esophageal tumors from 0% in zinc sufficient (ZS) ZS:p53+/+ mice to approximately 40%. On the p53+/- background, ZD:p53+/- mice had significantly greater tumor incidence and multiplicity than ZS:p53+/- and ZD:p53+/+ mice, with a high frequency of progression to malignancy. Sixty-nine and 31% of ZD:p53+/- lingual and esophageal tumors, respectively, were squamous cell carcinoma versus 19 and 0% of ZS:p53+/- tumors (tongue, P = 0.003; esophagus, P = 0.005). Immunohistochemical analysis revealed that the increased cellular proliferation observed in preneoplastic lingual and esophageal lesions, as well as invasive carcinomas, was accompanied by overexpression of cytokeratin 14, cyclooxygenase-2 and metallothionein. In summary, a new UADT cancer model is developed in ZD:p53+/- mouse that recapitulates aspects of the human cancer and provides opportunities to probe the genetic changes intrinsic to UADT carcinogenesis and to test strategies for prevention and reversal of this deadly cancer.

Topics: 4-Nitroquinoline-1-oxide; Animals; Biomarkers, Tumor; Carcinogens; Cyclooxygenase 2; Disease Models, Animal; Esophageal Neoplasms; Female; Gene Expression; Genetic Predisposition to Disease; Immunohistochemistry; Keratin-14; Keratins; Male; Metallothionein; Mice; Mice, Mutant Strains; Precancerous Conditions; Tongue Neoplasms; Tumor Suppressor Protein p53; Zinc

Esophageal cancers are predominantly carcinomas, which are-due to their origin from the epithelial lining-visible by endoluminal view. We report in this study about the rare case of an esophageal squamous cell cancer with an unusual, entirely intramural growth pattern. The diagnosis could only be established postoperatively, because all preoperative biopsies had failed to demonstrate the tumor. The entirely intramural growth pattern of esophageal squamous cell cancer is an exceedingly rare variant, with only one previously reported case. Nevertheless, clinicians, radiologists, and pathologists should be aware of the potential existence of this condition, especially when clinical and imaging results suggest a malignant tumor that cannot be proven on biopsies. Surgical exploration must be considered under these circumstances.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Count; Disease-Free Survival; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Treatment Outcome

Esophageal cancer remains a highly lethal malignancy for which the genetic and proteomic events are poorly understood. Studies have reported dysregulated proteins in esophageal carcinoma; however, the magnitude of these changes remains largely uncharacterized. Little is known about alterations early in the neoplastic pathway. Using multiplex tissue immunoblotting, we quantified the expression of seven proteins in esophageal carcinogenesis. Regions of normal, dysplasia, and invasive carcinoma of the squamous esophagus in six patients were characterized. Pan-cytokeratin (CK) was essentially unchanged across the transition (0.96 in dysplasia and 0.69 in tumor). Expression levels of annexin 1, CK-4, and CK-14 were all decreased in dysplasia and tumor compared with normal (reference, 1.00): annexin 1, 0.30 in dysplasia and 0.15 in tumor; CK-4, 0.20 in dysplasia and 0.16 in tumor; and CK-14, 0.54 in dysplasia and 0.40 in tumor. Expression of two proteins was increased in dysplasia and tumor versus normal: cyclooxygenase-2, 1.35 in dysplasia and 2.32 in tumor and p53, 1.29 in dysplasia and 2.37 in tumor. Secreted protein, acidic and rich in cysteine, which is expressed in the adjacent stroma, was 1.56-fold higher in stroma underlying dysplasia and 6.20-fold increased in dysplastic stroma surrounding invasive tumor. These findings suggest that changes in protein expression can be detected during the transition to dysplasia and may be useful biomarkers.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Esophageal Neoplasms; Esophagus; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; Keratins; Molecular Diagnostic Techniques; Neoplasm Invasiveness; Osteonectin; Pilot Projects; Precancerous Conditions; Proteome; Tumor Suppressor Protein p53

The genetic bases underlying esophageal tumorigenesis are poorly understood. Our previous studies have shown that coordinated deletion of the Smad4 and PTEN genes results in accelerated hair loss and skin tumor formation in mice. Herein, we exemplify that the concomitant inactivation of Smad4 and PTEN accelerates spontaneous forestomach carcinogenesis at complete penetrance during the first 2 months of age. All of the forestomach tumors were invasive squamous cell carcinomas (SCCs), which recapitulated the natural history and pathologic features of human esophageal SCCs. A small population of the SCC lesions was accompanied by adenocarcinomas at the adjacent submucosa region in the double mutant mice. The rapid progression of forestomach tumor formation in the Smad4 and PTEN double knockout mice corresponded to a dramatic increase in esophageal and forestomach epithelial proliferation. The decreased expression of p27, p21, and p16 together with the overexpression of cyclin D1 contributed cooperatively to the accelerated forestomach tumorigenesis in the double mutant mice. Our results point strongly to the crucial relevance of synergy between Smad4 and PTEN to suppress forestomach tumorigenesis through the cooperative induction of cell cycle inhibitors.

Topics: Animals; Carcinoma, Squamous Cell; Cell Growth Processes; Cell Transformation, Neoplastic; Cyclin D; Cyclins; Down-Regulation; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Keratins; Mice; Mice, Knockout; Mice, Transgenic; Mutation; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Smad4 Protein; Stomach Neoplasms

Mucosal ablation and endoscopic mucosal resection have been proposed as alternatives to surgical resection as therapy for intramucosal adenocarcinoma (IMC) of the esophagus. Acceptance of these alternative therapies requires an understanding of the clinical biology of IMC and the results of surgical resection modified for treatment of early disease.. Retrospective review of 78 patients (65 men, 13 women; median age 66 years) with IMC who were treated with progressively less-extensive surgical resections (ie, en bloc, transhiatal, and vagal-sparing esophagectomy) from 1987 to 2005.. The tumor was located in a visible segment of Barrett's esophagus in 65 (83%) and in cardia intestinal metaplasia in 13 (17%). A visible lesion was present in 53 (68%) and in all but 4 the lesion was cancer. In those patients with visible Barrett's, the tumor was within 3 cm of the gastroesophageal junction in 66% and within 1 cm in 37%. Esophagectomy was en bloc in 23, transhiatal in 31, vagal-sparing in 20, and transthoracic in 4. Operative mortality was 2.6%. Vagal-sparing esophagectomy had less morbidity, a shorter hospital stay, and no mortality. Of the patients who had en bloc resection, a median of 41 nodes were removed. One patient had one lymph node metastasis on hematoxylin and eosin staining and two others, normal on hematoxylin and eosin staining, had micrometastases on immunohistochemistry. Actuarial survival at 5 years was 88% and was similar for all types of resections. Two patients died from systemic metastases and seven from noncancer causes.. IMC occurred in cardia intestinal metaplasia and in Barrett's esophagus. Two-thirds of patients with IMC had a visible lesion. Most tumors occurred near the gastroesophageal junction. Node metastases were uncommon, questioning the need for lymphadenectomy. A vagal-sparing technique had less morbidity than other forms of resection and no mortality. Survival after all types of resection was similar. Outcomes of endoscopic techniques should be compared with this benchmark.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Biopsy; Esophageal Neoplasms; Esophagectomy; Esophagoscopy; Female; Follow-Up Studies; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Male; Middle Aged; Retrospective Studies; Treatment Outcome

We report three cases of leiomyoma of the gastrointestinal tract with intracytoplasmic inclusion bodies similar to those characteristic of inclusion body fibromatosis (IBF). The first two cases represent leiomyoma of the stomach: one in a 70-year-old female and the other in a 72-year-old female. In both instances inclusion bodies were present in a large amount. In the third case the leiomyoma was located in the esophagus of a 63-year-old male and inclusion bodies in this case were rare. In all three cases an immunohistochemical analysis showed positivity of the tumor cells for muscle specific actin HHF35 (MSA), alpha-smooth muscle actin (SMA), h-caldesmon and desmin. The first case showed some inclusion bodies with positivity for cytokeratin CAM 5.2 and focal weak positivity for cytokeratin 18. In the second case the inclusion bodies were positive at the periphery with antibodies directed against MSA and SMA. In the third case the inclusion bodies were immunohistochemically entirely negative. Ultrastructurally, the inclusion bodies in the first case were composed of aggregated filaments, some with entrapped cytoplasmic organels and others with finely granular dense cores.

Topics: Actins; Aged; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Inclusion Bodies; Keratins; Leiomyoma; Male; Middle Aged; Neoplasms, Multiple Primary; Stomach Neoplasms

Primary small cell carcinoma of esophagus (SCC) is a rare disease but has more aggressive behavior than esophageal squamous cell carcinoma (SQC). The distinction of SCC from SQC is very important therapeutically. Few systematic studies of immunohistochemical analysis to differentiate primary esophageal SCC with concomitant SQC, and adjacent normal esophageal epithelium have been reported. The objective of this study is to know the immunohistochemical markers in distinguishing SCC from SQC of esophagus. We studied 6 cases of primary esophageal SCC histologically and immunohistochemically using 15 different antibodies including a cytokeratin (CK) panel and neuroendocrine markers. Pure SCCs were identified in 2 of the 6 cases (33.3%), and the remaining 4 cases (66.7%) were found to exhibit combined SCC with an SQC component. Among the combined types, in situ SQC was observed in all 4 cases (100.0%) and invasive SQC was observed in 3 cases (75.0%). Among the normal esophageal epithelia specimens (n=7), CK14 expression was seen 6 out of 7 (85.7%) specimens and CKAE1/3 in 5 out of 7 (71.4%) specimens. CD56 was more frequently expressed among the SCC specimens (4/6; 66.7%) than among the SQC specimens (0/4; 0%; p = 0.07). The expression of p53 protein in SCC (4/6; 66.7%) and SQC (3/4; 75.0%) specimens was significantly more frequent than in normal esophageal epithelium (0/7; 0%; p = 0.02 each). Neurone-specific enolase (NSE), synaptophysin, and CKAE1/3 were expressed in 83.3%, 66.7%, and 66.7% of the SCC cases (n=6), respectively. NSE expression was significantly more frequent in SCC specimens (5/6; 83.3%) (p = 0.02) than in normal esophageal epithelium (0/7; 0%; p = 0.02). However, the frequencies of NSE expression in SCC (5/6; 83.3%) and SQC (2/4; 50%) were not significantly different. All of the SQC specimens (n=4) expressed CK14 and CKAE1/3. The CK14 expression was significantly more frequent in SQC specimens (4/4; 100.0%) than in (p = 0.04) SCC specimens (1/6; 16.6%; p = 0.04). These findings suggest that the CK14 and CD56 may be useful markers for differentiating SQC from SCC and vice versa. The p53 may also be useful to differentiate normal esophageal epithelium from SCC or SQC tissue.

Topics: Carcinoma, Small Cell; Carcinoma, Squamous Cell; CD56 Antigen; Diagnosis, Differential; Epithelium; Esophageal Neoplasms; Humans; Immunochemistry; Keratins

This study was designed to evaluate molecular markers for the detection of micrometastasis in esophageal adenocarcinoma, define algorithms to distinguish positive from benign lymph nodes and to validate these findings in an independent tissue set and in patients with p(N0) esophageal adenocarcinoma.. Potential markers were identified through literature and database searches. All markers were analyzed by quantitative reverse transcription (QRT)-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set and classification algorithms were generated for individual markers and combinations. Algorithms were statistically validated internally as well as externally on an independent set of lymph nodes. Selected markers were then used to identify occult disease in lymph nodes from 34 patients with p(N0) esophageal adenocarcinoma.. Thirty-nine markers were evaluated, six underwent further analysis and five were analyzed in the external validation study. Two markers provided perfect classification in both the screening and validation sets, although parametric bootstrap analysis estimated 2% to 3% optimism in the observed classification accuracy. Several marker combinations also gave perfect classification in the observed data sets, and estimates of optimism were lower, implying more robust classification than with individual markers alone. Five of thirty-four patients with esophageal adenocarcinoma had positive nodes by multimarker QRT-PCR analysis and disease-free survival was significantly worse in these patients (P = 0.0023).. We have identified novel QRT-PCR markers for the detection of occult lymph node disease in patients with esophageal adenocarcinoma. The objective nature of QRT-PCR results, and the ability to detect occult metastases, make this an attractive alternative to routine pathology.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Adhesion Molecules; Epithelial Cell Adhesion Molecule; Esophageal Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymph Nodes; Lymphatic Metastasis; Microfilament Proteins; Neoplasm Staging; Predictive Value of Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Survival Analysis

Aim of this study was to examine the presence and the prognostic impact of immunohistochemically identified nodal micrometastases in patients with gastro-oesophageal junction (GEJ) carcinomas.. Between January 1988 and December 2000, 148 patients underwent a radical (R0) resection with a two-field lymphadenectomy for a GEJ carcinoma. Specimens of 60 patients in whom conventional haematoxylin and eosin (H & E) examination did not demonstrate lymph-node metastases (pN0) were available for immunohistochemical (IHC) analysis using antibodies AE1/AE3 directed against cytokeratins. Paraffin embedded material of all retrieved lymph nodes in these patients were serially sectioned and analysed by one pathologist after H & E examination for the presence of micrometastases by IHC.. In 60 resection specimens initially staged as pN0 a total of 524 lymph nodes were available for IHC analyses. Micrometastases were detected in 126 out of 524 lymph nodes (24%), corresponding with 18 of the 60 patients (30%) who were upstaged by this technique. Compared with the pN0 group, the disease free survival (DFS) was significantly lower in patients with nodal involvement at IHC (p<0.001). Survival of patients with IHC identified micrometastatic disease was comparable to those with H & E positive lymph nodes.. Micrometastases in regional nodes were detected by cytokeratin-specific IHC in 30% of radical resected GEJ tumours without overt nodal involvement. Their presence conveys a worse prognosis with a significant reduced DFS, suggesting that the finding of micrometastases should be included in the staging system.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Stomach Neoplasms

It is sometimes difficult to distinguish between cardia cancer and oesophageal cancer.. To evaluate whether cytokeratin (CK) expression of the tumour can be of value in differentiating between the two tumour types.. Consecutive patients with a malignant tumour in the oesophagus or stomach were recruited. Biopsy specimens were taken for routine haematoxylin and eosin staining. One tissue block with representative tissue was selected for immunohistochemical staining (CK7 and CK20).. Endoscopically located adenocarcinoma of the oesophagus was present in 84 patients (64 men, 20 women; mean age, 68 years; range, 44-91). Cancer located primarily in the gastric cardia was present in 63 patients (42 men, 21 women; mean age, 68 years; range, 42-88). The histological diagnosis was metastasis from a primary tumour outside the oesophagus or stomach in 19 patients. The patients were divided into three groups for the immunohistochemical analysis. Patients in group A had definite oesophageal cancer, group B patients had a definite carcinoma located in the gastric cardia, and group C patients had an obstructing tumour distal in the oesophagus at the level of the diaphragm, which could not be passed with the endoscope. Paraffin wax embedded material was available from 122 patients for immunostaining and CK analysis. There was no significant difference in expression or distribution of CK7 or CK20 in the three groups of patients.. CK phenotyping cannot distinguish between cancer arising from a Barrett's oesophagus and carcinoma originating in the gastric cardia.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cardia; Diagnosis, Differential; Esophageal Neoplasms; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Precancerous Conditions; Stomach Neoplasms

Osteopontin (OPN) is a secreted integrin-binding glycophosphoprotein that may have a role in head and neck squamous cell carcinoma (SCC). To evaluate the clinical significance of OPN in esophageal squamous cell carcinoma (ESCC), we compared plasma OPN levels with those of common tumor markers.. Preoperative plasma OPN levels were measured by enzyme immunoassay in 103 ESCC patients. Serum SCC antigen, Cyfra 21-1, and carcinoembryonic antigen (CEA) levels were also measured routinely at admission by radioimmunoassay.. Plasma OPN levels ranged from 82.8 to 1,980 ng/ml. High OPN level was associated with lymph node metastasis (p = 0.05), but not with tumor histology or depth of invasion. The overall survival of the patients with high OPN levels was worse than that of those with low OPN levels (p = 0.02). SCC antigen and Cyfra 21-1 levels were associated with the depth of tumor invasion, the tumor diameter, lymph node metastasis, and the overall survival, but CEA was not associated with these clinicopathological factors. Combined evaluation of OPN plus Cyfra 21-1 or OPN plus SCC antigen was useful as an independent prognostic indicator.. Measurement of the plasma OPN level, as well as serum SCC antigen and Cyfra 21-1, may help to predict the progression of ESCC.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Multivariate Analysis; Osteopontin; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Serpins; Sialoglycoproteins; Survival Analysis

Zinc deficiency in rats enhances esophageal cell proliferation, causes alteration in gene expression, and promotes esophageal carcinogenesis. Zinc replenishment rapidly induces apoptosis in the esophageal epithelium thereby reversing cell proliferation and carcinogenesis. To identify zinc-responsive genes responsible for these divergent effects, we did oligonucleotide array-based gene expression profiling analyses in the precancerous zinc-deficient esophagus and in zinc-replenished esophagi after treatment with intragastric zinc compared with zinc-sufficient esophagi. Thirty-three genes (21 up-regulated and 12 down-regulated) showed a > or = 2-fold change in expression in the hyperplastic zinc-deficient versus zinc-sufficient esophageal epithelia. Expression of genes involved in cell division, survival, adhesion, and tumorigenesis were markedly changed. The zinc-sensitive gene metallothionein-1 (MT-1 was up-regulated 7-fold, the opposite of results for small intestine and liver under zinc-deficient conditions. Keratin 14 (KRT14, a biomarker in esophageal tumorigenesis), carbonic anhydrase II (CAII, a regulator of acid-base homeostasis), and cyclin B were up-regulated >4-fold. Immunohistochemistry showed that metallothionein and keratin 14 proteins were overexpressed in zinc-deficient esophagus, as well as in lingual and esophageal squamous cell carcinoma from carcinogen-treated rats, emphasizing their roles in carcinogenesis. Calponin 1 (CNN1, an actin cross-linking regulator) was down-regulated 0.2-fold. Within hours after oral zinc treatment, the abnormal expression of 29 of 33 genes returned to near zinc-sufficient levels, accompanied by reversal of the precancerous phenotype. Thus, we have identified new molecular markers in precancerous esophagus and showed their restoration by zinc replenishment, providing insights into the interaction between zinc and gene expression in esophageal cancer development and prevention.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinoma, Squamous Cell; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Immunohistochemistry; Keratin-14; Keratins; Male; Metallothionein; Precancerous Conditions; Rats; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation; Zinc

Small cell carcinoma is a rare malignant disease with high mortality, which is pathologically diagnosed by using routine neuroendocrinal markers, such as neuron-specific enolase (NSE), synaptophysin (SYN), chromogranin A (CgA). This study was to investigate the expression of CD56, a neural cell adhesion molecule (NCAM), in small cell carcinoma tissues, and to explore the possibility of CD56 as a diagnostic marker of small cell carcinoma.. Eighty samples of small cell carcinoma were collected, including 42 samples of small cell lung carcinoma (with 20 cases of lymph node metastases), 21 samples of small cell esophageal carcinoma, and 17 samples of small cell colorectal carcinoma. Thirty-eight samples of non-small cell lung cancer (with 28 cases of lymph node metastases), including 26 samples of squamous cell carcinoma and 12 samples of adenocarcinoma, were used as control. All samples were detected using markers of CD56, NSE, SYN, CgA, cytokeratin (CK), and epithelial membrane antigen (EMA) immunohistochemically.. Positive rate of CD56 was significantly higher in either small cell lung carcinoma or their metastatic lymph nodes than in either non-small cell lung carcinoma or their metastatic lymph nodes [90.5% (38/42) vs. 7.8% (3/38), 90.0% (18/20) vs. 3.5% (1/28); H=85.731, P<0.001]. Positive rate of CD56 in small cell carcinoma samples (86.3%, 69/80) were significantly higher than those of SYN (78.8%, 63/80), CgA (73.8%, 59/80), EMA (66.3%, 53/80), CK (61.3%, 49/80), and NSE (56.3%, 45/80) (H=38.871, P<0.001). Positive rate of CD56 in small cell lung carcinoma (90.5%, 38/42) was similar to those in small cell esophageal carcinoma (81.0%, 17/21) and small cell colorectal carcinoma (82.4%, 14/17) (H=1.651, P=0.438).. CD56 is highly expressed in either small cell carcinoma or their metastatic lymph nodes without organ-specificity. It could serve as a potential diagnostic marker of small cell carcinoma.

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; CD56 Antigen; Chromogranin A; Colorectal Neoplasms; Diagnosis, Differential; Esophageal Neoplasms; Follow-Up Studies; Humans; Keratins; Lung Neoplasms; Lymphatic Metastasis; Mucin-1; Phosphopyruvate Hydratase; Synaptophysin

Esophageal carcinoma is the seventh most common cause of cancer-related death in the Western world. In Sweden, approximately 400 new esophageal carcinomas are diagnosed yearly. Cytokeratins (CK) are specific for epithelial cells and the expression profile usually remains unchanged even when the epithelium undergoes malignant transformation. In the present study, MonoTotal, a newly developed RIA-assay detecting circulating CK 8, 18 and 19 fragments, was investigated in sera from patients with esophageal carcinoma. Serum samples from 40 patients with esophageal carcinoma were collected. The median value of circulating CK 8, 18 and 19 measured with MonoTotal was 378 U/L (range 53-6843) and with regard to the defined cut-off (< 75 U/L), 39/40 (98%) patients were shown to have elevated levels of circulating CK 8, 18 and 19. Patients with localized disease had a median value of circulating CK 8, 18 and 19 of 305 U/L (mean: 500 U/L), whereas the corresponding value for metastatic disease was 771 U/L (mean: 1506 U/L). This difference was statistically significant (P = 0.016). Circulating CK 8, 18 and 19, according to cut-off, were not associated with survival in univariate analysis (P = 0.34). However, continuous values of circulating levels of CK 8, 18 and 19 were associated with survival (P = 0.000083) in univariate as well as in the multivariate analysis (P = 0.03). In conclusion, circulating CK 8, 18 and 19 correlates with increased tumor burden and might, in conjunction with other clinical parameters, aid the clinician in estimating the prognosis of the individual patient.

Topics: Esophageal Neoplasms; Female; Humans; Immunoradiometric Assay; Keratins; Male; Multivariate Analysis; Prognosis; Survival Analysis

The correlation between detection of occult neo-plastic cells (ONCs) in lymph node sinuses and the recurrence/metastasis of primary breast, lung, esophageal, and gastric cancer was examined. Among patients with Stage I-III cancer treated by radical resection with dissection of at least 10 lymph nodes, 40 patients who suffered recurrence/metastasis within 5 years post-operatively and 94 patients who did not have recurrence within 5 years were randomly selected. A total of 1,340 lymph nodes were subjected to immunohistochemical staining for cytokeratin to identify ONCs. Then the sensitivity, specificity, positive predictive value, and negative predictive value of ONCs were determined for predicting the recurrence of each cancer. These parameters were respectively 40.0, 75.9, 62.4, and 55.8% for breast cancer, while the respective values were 50.0, 77.4, 68.9, and 60.8% for lung, 57.1, 64.3, 61.5, and 60.0% for esophageal, and 68.8, 65.0, 66.3, and 67.5% for gastric cancer. All of the parameters exceeded 65% for gastric cancer. ONCs also showed a high specificity for breast and lung cancer, but both the sensitivity and specificity were low for esophageal cancer.

Topics: Breast Neoplasms; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasms; Predictive Value of Tests; Random Allocation; Sensitivity and Specificity; Single-Blind Method; Stomach Neoplasms

Squamous cell carcinoma of the oral cavity is one of the most common human neoplasms, and prevention of these carcinomas requires a better understanding of the carcinogenesis process and a model system in which cancer chemoprevention agents can be tested. We have developed a mouse model using the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in the drinking water to induce tumorigenesis in the mouse oral cavity.. 4-NQO was delivered by tongue painting or drinking water to two mouse strains, CBA and C57Bl/6. The incidences of oral cavity carcinogenesis were then compared. In addition, we examined the expression of some of the molecular markers associated with the process of human oral cavity and esophageal carcinogenesis, such as keratin (K) 1, K14, p16, and epidermal growth factor receptor, by immunohistochemistry.. After treatment with 4-NQO in the drinking water, massive tumors were observed on the tongues of both CBA and C57Bl/6 female mice. Pathological analyses indicated that flat squamous dysplasias, exophytic papillary squamous tumors (papillomas), and invasive squamous cell carcinomas were present. Immunohistochemistry analyses showed that 4-NQO changed the expression patterns of the intermediate filament proteins K14 and K1. K14 was expressed in the epithelial suprabasal layers, in addition to the basal layer, in tongues from carcinogen-treated animals. In contrast, control animals expressed K14 only in the basal layer. Moreover, we observed more bromodeoxyuridine staining in the tongue epithelia of 4-NQO-treated mice. Reduced expression of the cell cycle inhibitor, p16, was observed, whereas 4-NQO treatment caused an increase in epidermal growth factor receptor expression in the mouse tongues. Interestingly, similar features of carcinogenesis, including multiple, large (up to 0.5 cm) exophytic papillary squamous tumors and invasive squamous cell carcinomas, increased bromodeoxyuridine staining, and increased K14 expression, were also observed in the esophagi of 4-NQO-treated mice. However, no tumors were observed in the remainder of digestive tract (including the forestomach, intestine, and colon) or in the lungs or livers of 4-NQO-treated mice. These results indicate that this murine 4-NQO-induced oral and esophageal carcinogenesis model simulates many aspects of human oral cavity and esophageal carcinogenesis.. The availability of this mouse model should permit analysis of oral cavity and esophageal cancer development in various mutant and transgenic mouse strains. This model will also allow testing of cancer chemopreventive drugs in various transgenic mouse strains.

Topics: 4-Nitroquinoline-1-oxide; Animals; Bromodeoxyuridine; Carcinogens; Carcinoma, Papillary; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Disease Models, Animal; ErbB Receptors; Esophageal Neoplasms; Female; Immunoenzyme Techniques; Keratin-14; Keratins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mouth Neoplasms; Neoplasm Invasiveness; Tongue Neoplasms

The clinical significance of micrometastasis in sentinel nodes (SNs) may differ in various organs. In particular, the prognostic value of SN micrometastases detected by reverse transcriptase-polymerase chain reaction (RT-PCR) is still controversial. We investigated the diagnostic and therapeutic significance of nodal molecular metastasis detected by nested RT-PCR for cytokeratin (CK) 19 mRNA in gastrointestinal cancer. In 51 cases with GI tract cancer treated by standard curative resection, SNs were identified by a radio-guided method. In 10 of 51 patients, 25 SNs and 3 non-SNs were histologically negative and RT-PCR positive. Three non-SNs with positive CK19 mRNA were randomly sampled from the same basin where histologically positive SNs were identified. Immunohistochemical analysis of six additional step sections obtained at 30- micro m intervals with use of an anticytokeratin antibody showed clearly recognizable histological metastases in 4 of 25 histologically negative/RT-PCR-positive SNs (16%). In one case of esophageal squamous cell carcinoma with nodal micrometastasis identified by CK19 RT-PCR, extranodal local recurrence in the SN basin (left supraclavicular basin) was observed 6 months postoperatively. These findings suggest that nodal micrometastasis detected by nested RT-PCR has some clinical significance in GI cancer. Molecular assessment of the SN may be a valuable tool to complement routine histological examination for GI cancers.

Topics: Esophageal Neoplasms; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Neoplasm Staging; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Sentinel Lymph Node Biopsy

Detection of micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of esophageal cancer patients. Bone marrow and peripheral blood samples were obtained from 52 squamous esophageal cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor (VEGF) and cyclin D1 was examined in the primary tumors. Cytokeratin-positive cancer cells were observed in the bone marrow of 13 (25%) out of 52 patients. Among them, three patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with lymph node metastasis (pN) but not associated with depth of tumors (pT). Detection of bone marrow micrometastasis was significantly correlated with VEGF expression of the primary tumors. Cumulative survival of patients with bone marrow micrometastasis was significantly lower than that of patients without it (p=0.0008). Hematogenous recurrence was more frequent in patients with bone marrow micrometastasis than in those without it (p=0.0004). Three patients who had local or dissemination recurrence did not have bone marrow micrometastasis. Detection of cancer cells in the bone marrow might be an indicator of early hematogenous metastasis in esophageal cancer patients. Intensive postoperative chemotherapy seems to be indicated for these patients.

Topics: Aged; Antigens, Neoplasm; Bone Marrow Neoplasms; Esophageal Neoplasms; Female; Humans; Immunomagnetic Separation; Keratin-19; Keratins; Male; Middle Aged; Serpins; Survival Analysis

A squamous cell carcinoma (SCC) with sarcomatous features (so-called carcinosarcoma) of stomach is reported in a 72-year-old man. The gastric submucosal tumor (12 x 11 x 6 cm) consisted of carcinoma cells and sarcomatous spindle cells, which were immunohistochemically recognized to contain high molecular weight cytokeratin. These histological and immunohistochemical results indicated that carcinoma cells and spindle tumor cells had cytokeratin similar to that of stratified squamous epithelium. These features were consistent with so-called carcinosarcoma of esophagus. A combined type of tumor consisting of polypoid and shallow ulcerative lesions (5.5 cm in diameter) was demonstrated by the biopsy to have SCC on the polypoid surface area. Therefore, the gastric tumor was thought to have metastasized from the esophageal tumor. The quick-freezing and deep-etching (QF-DE) method demonstrated that many spindle tumor cells in the gastric tumor had abundant intermediate filaments, which were evenly distributed in more peripheral cytoplasm along the cell membrane. This feature was similar to that of the control SCC. Intramembranous protein particles in the cell membrane of the tumor cells were markedly decreased as compared with those of control SCC. These ultrastructures by QF-DE method could be used for the pathological diagnosis of so-called carcinosarcomas of esophagus.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Esophageal Neoplasms; Freeze Etching; Humans; Keratins; Male; Microscopy, Electron; Stomach Neoplasms

In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.

Topics: Adult; Aged; Biomarkers, Tumor; Blotting, Western; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Cell Line, Tumor; Cell Transformation, Neoplastic; Esophageal Neoplasms; Female; Fluorescent Antibody Technique, Indirect; Glucuronidase; Humans; Immunoenzyme Techniques; In Situ Hybridization; Keratins; Male; Middle Aged; Prognosis; Proliferating Cell Nuclear Antigen; RNA, Messenger; Survival Rate

The number or ratio of lymph node metastases detected by hematoxylin & eosin (H&E) staining is the most important predictor of survival in esophageal cancer. The survival effect of lymph node metastases detected on immunohistochemistry (IHC) is controversial. My colleagues and I hypothesized that the extent of nodal disease determined by both H&E and IHC examination would more accurately predict survival than either technique alone.. The study population consisted of 37 patients who underwent en bloc esophagectomy as primary therapy for esophageal adenocarcinoma 5 or more years ago. All had mediastinal and upper abdominal lymphadenectomy. No patient received neoadjuvant or adjuvant therapy. Tissue blocks were sectioned for H&E staining to confirm the initial histology, and a second slide was stained with monoclonal antibodies AE1 and CAM 5.2, which are directed at a number of cytokeratin antigens. The slides were reviewed by an investigator blinded to clinical outcome. The effect of IHC staining on prognosis was assessed by comparing 5-year survival based on H&E and IHC findings.. A total of 1,970 nodes were examined in the 37 patients. Routine H&E staining detected metastases in 29 patients (78%); the remaining 8 with N0 disease all survived at least 5 years after operation (median not reached). In the 29 patients with N1 disease, survival was 41% at 5 years. In 20 of the 29 N1 patients, metastases were detected by H&E in less than 10% of the nodes removed; 55% of the patients survived 5 years, and 39% survived 8 years. Nine of the 29 patients had metastases detected in more than 10% of the nodes removed, and all died at a median of 17 months. IHC staining was performed on the nodes from the 8 N0 patients and the 20 patients with less than 10% nodal involvement (a total of 28 patients). Additional nodal metastases, not identified on H&E examination, were found in 51 nodes from 17 patients (60.7%). Of the 8 patients who were node negative on H&E examination, 3 had metastases detected by IHC, and all survived 5 years or more free of disease. Of the 20 patients with less than 10% nodal metastases on H&E, 14 (70%) had additional metastases detected by IHC (median, 2 nodes per patient). When combined with the results of H&E staining, the node ratio remained less than 10% in 13 patients and exceeded 10% in 7. Survival in patients whose ratio remained less than 10% was significantly better than in those whose ratio exceeded 10% (actual 5-year survival, 77% vs 14%; chi2 = 4.662; p = 0.03).. IHC staining techniques can identify nodal metastases missed by routine H&E examination in a large number of patients. The combination of H&E and IHC examination is useful in patients with less than 10% nodal involvement by H&E examination in that IHC detection of micrometastases allows classification into low-risk (> 75% survival) and high-risk (< 15% survival) groups. IHC-detected micrometastases are not of prognostic importance in N0 patients or those with greater than 10% nodal metastases on H&E.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Chi-Square Distribution; Coloring Agents; Eosine Yellowish-(YS); Esophageal Neoplasms; Esophagectomy; Female; Follow-Up Studies; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Life Tables; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Prognosis; Single-Blind Method; Staining and Labeling; Survival Analysis

The p53 tumor suppressor protein plays a pivotal role in preventing uncontrolled cellular proliferation. By contrast, zinc deprivation enhances esophageal cell proliferation and the induction of esophageal tumors in rodents by N-nitrosomethylbenzylamine (NMBA). We investigated whether p53 deficiency rendered zinc-deficient (ZD) mice more susceptible to NMBA-induced esophageal/forestomach carcinogenesis. At 6-7 weeks of age, p53 null (-/-), heterozygous (+/-), and wild-type (+/+) mice were placed on ZD or zinc-sufficient (ZS) diets to form six experimental groups: ZD:p53-/-; ZD:p53+/-; ZD:p53+/+; ZS:p53-/-; ZS:p53+/-; and ZS:p53+/+. After 3 weeks, 15-23 mice in each group were treated once with NMBA (2 mg/kg body weight). Control animals were untreated. Zinc deficiency alone induced unrestrained cellular proliferation in the esophagus and forestomach of p53-/- mice. Forestomach tumors were first detected in a ZD:p53-/- mouse at 13 days. By 30 days, 100% (21 of 21) of ZD:p53-/- mice developed forestomach tumors and 38% showed esophageal tumors versus 42 and 0% in ZS:p53-/- mice (P < 0.004, esophagus; P < 0.001, forestomach). ZD:p53-/- mice showed an accelerated progression to malignancy, with 10% of esophageal tumors and 38% of forestomach tumors presenting as carcinomas. Nearly 20% of ZD:p53-/- mice developed esophageal Barrett's metaplasia, a lesion not previously seen in NMBA-induced neoplasia. ZD:p53+/- mice had significantly higher tumor incidence than ZS:p53+/- mice. The order of tumor incidence in forestomach was as follows: naught incidence in ZS:p53+/+ mice; ZD:p53-/- > ZD:p53+/- > ZS:p53-/- > ZD:p53+/+ >/= ZS:p53+/- > ZS:p53+/+. The rapid rate of tumor induction/progression in ZD:p53-/- mice was accompanied by an increase in the rate of cell proliferation and a decrease in apoptosis. cDNA array expression analysis of known genes identified a 5-fold up-regulation of cytokeratin 14 mRNA expression in ZD:p53-/- versus ZS:p53-/- forestomach, a result showing gene-modulating effects of zinc deficiency. Cytokeratin 14 is a biomarker in human esophageal carcinogenesis. Our findings provide in vivo evidence for the collaboration of a deficiency of both p53 and zinc in esophageal carcinogenesis and reveal molecular targets of this collaboration.

Topics: Animals; Carcinogens; Cell Division; Crosses, Genetic; Diet; Dimethylnitrosamine; Disease Progression; Esophageal Neoplasms; Genotype; Keratins; Mice; Mice, Knockout; Polymerase Chain Reaction; Stomach Neoplasms; Tumor Suppressor Protein p53; Zinc

In this study, 62 preoperative peripheral blood samples from patients with gastrointestinal carcinomas, 12 healthy volunteers, and ten patients with inflammatory gastrointestinal diseases were analyzed for the determination of CEA, CK19, and CK20 mRNA expression in peripheral blood, and its clinical significance was evaluated.. Nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) was used to analyze CEA, CK19, and CK20 mRNA expression in peripheral blood. Fresh tumor tissues from patients with colorectal cancer (n=15) were used as a positive control.. Among 62 blood samples from patients with gastrointestinal cancer, the expression of CEA, CK19, and CK20 mRNA was 51.6% (32/62), 35.5% (22/62), and 48.4% (30/62), respectively. 74.2% (46/62) were positive for at least one marker. Fifteen tumor tissues were all positive for CEA, CK19, and CK20 mRNA. Only one blood sample from patients with no gastrointestinal carcinoma was positive for CEA mRNA.. Our results indicate that the molecular detection of circulating tumor cells in peripheral blood in patients with gastrointestinal carcinoma was significantly correlated with its malignant biological properties, and may be helpful in the selection of clinical treatment and judgment of prognosis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Case-Control Studies; Colorectal Neoplasms; DNA Primers; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm

CYFRA 21-1 has been reported as a useful tumor marker for esophageal carcinoma, but little information was reported about the clinicopathologic importance of CYFRA 21-1. The aim of this study was to analyze the clinicopathologic and prognostic significance of preoperative CYFRA 21-1 in patients with esophageal squamous cell carcinoma.. The CYFRA 21-1 levels were measured before surgery by enzyme-linked immunosorbent assays in 157 patients with primary esophageal squamous cell carcinomas using 3.5 ng/mL as the upper limit of normal. All patients underwent radical surgical procedures without any preoperative therapy. The association between the clinicopathologic factors assessed and the CYFRA 21-1 level was determined. The CYFRA 21-1 values were monitored after surgery in 45 available patients. The prognostic values were determined by multivariate analysis using Cox's proportional hazards model.. Thirty-one of the 157 patients (19.7%) had high CYFRA 21-1 levels (> or =3.5 ng/mL). CYFRA 21-1 levels were significantly increased in patients with large tumors (> or =40 mm, p = 0.009), deep tumors (T2-T4, p = 0.003), and node-positive tumors (p = 0.003). CYFRA 21-1 levels significantly decreased after surgery (p < 0.001). A high CYFRA 21-1 level before surgery was an independent prognostic factor for survival (p = 0.043).. A high CYFRA 21-1 level is associated with tumor progression and poor survival in patients with esophageal squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease Progression; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Statistics, Nonparametric

The intraoperative diagnosis of lymph node micrometastasis (LNM) may help guide the area of appropriate lymph node dissection. This study aimed to evaluate the rapid immunohistochemical detection of LNMs using frozen sections during operation for gastro-oesophageal cancer.. Rapid immunostaining with anticytokeratin (AE1/AE3) antibody was compared with conventional immunostaining. A total of 210 lymph nodes obtained from 47 patients with oesophageal squamous cell carcinoma and from 32 with gastric adenocarcinoma were examined during operation. Lymph nodes were frozen, sectioned, and examined by histological and immunohistochemical methods.. It took 30 min to complete the rapid immunostaining procedure; the expression of cytokeratin by rapid immunostaining was similar to that by conventional immunostaining. The incidence of lymph node metastasis detected by histological and immunohistochemical examination was 17 and 23 per cent respectively. LNM was solely detected in 12 lymph nodes by immunostaining: three micrometastases and nine with tumour cell microinvolvement.. : Intraoperative rapid immunostaining is a simple and useful technique for detecting LNMs. Further study should investigate the role of rapid immunostaining during cancer surgery to select appropriate areas for lymphadenectomy.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Intraoperative Care; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms

Topics: Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Esophageal Neoplasms; Humans; Ifosfamide; Keratin-7; Keratins

Intestinal metaplasia is a histologic hallmark of Barrett's esophagus and chronic gastritis. Intestinal metaplasia may progress to dysplasia or carcinomas without proper treatment. Most cases of intestinal metaplasia are easily recognized on hematoxylin and eosin-stained sections. However, some cases of intestinal metaplasia may be hard to recognize if they lack the characteristic mucin-producing cells and Paneth cells, or if they are small in size. Recently, keratin 7, keratin 20, and MUC2 expression patterns were reported to be useful in confirming the diagnosis of intestinal metaplasia. We studied hepatocyte (Hep) antigen (a hepatocellular antigen mainly expressing in normal and neoplastic hepatic tissues) in 33 cases of Barrett's esophagus (9 cases associated with esophageal adenocarcinoma) and 13 cases of chronic gastritis associated with intestinal metaplasia and gastric adenocarcinoma. Hep monoclonal antibody recognizes intestinal metaplasia in all cases. We also compared expression of Hep with that of keratin 7, keratin 20, and MUC2 in intestinal metaplasia. The specificity and sensitivity of Hep for intestinal metaplasia were higher than that of keratin 7 and keratin 20, or MUC2. We conclude that Hep may be used as a single diagnostic marker for intestinal metaplasia.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Barrett Esophagus; Biomarkers, Tumor; Chronic Disease; Esophageal Neoplasms; Gastritis; Hepatocytes; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Metaplasia; Mucin-2; Mucins; Precancerous Conditions; Sensitivity and Specificity; Stomach Diseases

Adenocarcinomas of the distal oesophagus and especially the oesophago-gastric junction have shown an increasing incidence during the last decade. Definition of subgroups according to different sites of development, histogenesis or aetiology may prove to be valuable for clinical diagnosis and treatment. Previous studies have shown differences in cytokeratin patterns between Barrett's metaplasia of the oesophagus and intestinal metaplasia in the stomach. The aim of our study was to investigate whether the expression of certain cytokeratins (CK7, CK20) and mucins (MUC1, MUC2, MUC5AC) exhibit clear-cut patterns, thus allowing a subclassification of adenocarcinomas of the oesophago-gastric junction. The possibility of a relationship between antigen expression and the presence or absence of Barrett's metaplastic epithelium was also studied.. CK7, CK20, MUC1, MUC2 and MUC5AC were visualized in six adenocarcinomas of the distal oesophagus, 29 adenocarcinomas of the oesophago-gastric junction and eight adenocarcinomas of the proximal stomach. CK7, CK20 and MUC1 were strongly expressed in the great majority of all neoplasms under study, whereas MUC2 and MUC5AC were absent or only faintly detectable. CK20 exhibited a significantly stronger expression in poorly differentiated tumours (G3) and MUC1 immunoreactivity correlated with tubular and papillary versus signet-ring cell histopathology. Other statistically significant correlations between antigens and histopathological features (pTNM stage, grading, histopathological subtype, presence/absence of Barrett's epithelium) were not observed.. According to our results, most adenocarcinomas of the oesophago-gastric junction show a CK7+, CK20+, MUC1+ phenotype irrespective of the presence or absence of Barrett's epithelium. The immunohistochemical data suggest a similar histogenesis of these tumours.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Cardia; Esophageal Neoplasms; Esophagogastric Junction; Humans; Immunohistochemistry; Keratins; Metaplasia; Mucins; Neoplasm Staging; Stomach Neoplasms

With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology.. Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed.. 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series.. Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.

Topics: Aged; Aged, 80 and over; Biopsy; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Tumor Suppressor Protein p53

To study the clinical significance of serum CEA, SCC and Cyfra21-1 test in the diagnosis, prediction of prognosis and postoperative monitor of recurrence in esophageal cancer.. The concentration of serum CEA and Cyfra21-1 was measured by electrochemiluminescence immunoassay (ECLIA) using Elecsys 2010, CEA kit and Cyfra21-1 kit. Serum SCC was measured by microparticle enzyme immunoassay (MEIA) using IMx System and SCC kit. Serum of 206 patients with esophageal cancer (203 squamous cell carcinoma, 2 small cell carcinoma and 1 adenosquamous carcinoma) was measured preoperatively, 71 of whom also measued 8 to 12 days after resection.. The cut-off value of CEA and Cyfra21-1 was < or = 3.25 ng/ml and < or = 2.61 ng/ml, which were determined by the data of 45 healthy Chinese measured during the same period. The positive ratios of serum CEA and Cyfra21-1 in 206 cases were 29.1% and 45.1%. The combined positive ratio of CEA and Cyfra21-1 was 57.3%. The CEA positive ratios, according to the pathological stage of 165 resectable patients, were 16.6% (stage I), 26.8% (II) and 30.8% (III). For Cyfra21-1, they were 27.8%, 37.5% and 50.5%. For CEA combined with Cyfra21-1, they were 38.9%, 50.0% and 63.7%. The mean value of CEA, SCC and Cyfra21-1 (especially SCC and Cyfra21-1) was found to be well correlated with the tumor volume, TNM stage and depth of tumor invasion. Patient with bulky tumor or advanced tumor (T4) usually had much higher mean value than those with early stage tumors. One week after radical resection, the level of the three tumor markers fell to normal level in 92.9% of 71 patients. The level of serum CEA and Cyfra21-1 varied greatly in a small part of the patients. Extremely elevated serum CEA and Cyfra21-1 usually indicated advanced lesion or tumor metastasis.. Preoperative and postoperative measurement of serum CEA, SCC and Cyfra21-1 (especially Cyfra21-1) is helpful in the diagnosis, prediction of prognosis and monitor of postoperative recurrence in patients with esophageal cancer.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoembryonic Antigen; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Menopause; Middle Aged; Serpins

The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6 immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ.. Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage.. CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a higher pTNM stage.

Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Mucins; Neoplasm Staging; Stomach Neoplasms

Abdominal para-aortic lymph node (APAL) dissection of esophageal cancer is not widely accepted. The aim of this article is to propose the indications for APAL dissection in esophageal cancer patients from the viewpoint of micrometastases.. To evaluate the value of APAL dissection in patients with esophageal cancer, the status of APAL metastases and recurrence in 230 patients with esophageal squamous cell carcinoma (1989 to 1998) was examined retrospectively. On the basis of our findings, 16 patients received a prophylactic APAL dissection from January 1999 to March 2001. Micrometastases in the dissected lymph nodes were examined using cytokeratin staining and reverse transcription-polymerase chain reaction of squamous cell carcinoma antigen messenger RNA.. Among the 230 patients who had esophageal squamous cell carcinoma, 21 had APAL metastases (including micrometastases) or APAL recurrence. Among the 21 patients with APAL metastases and recurrence, 20 (95.2%) had metastases (including micrometastases) in perigastric lymph nodes (paracardial and lesser curvature nodes). Among 51 patients with lower thoracic esophageal carcinoma, 13 (25.5%) had APAL metastases or recurrence. On the basis of these results, prophylactic APAL dissection was performed in patients with lower thoracic esophageal cancer who were suspected of perigastric lymph node metastases during operations. APAL metastases (including micrometastases) were detected in 6 (38%) of these patients, and 2 patients with APAL micrometastases survived without recurrence. However, 7 patients had hematogenic recurrence after the operation.. Our results suggested that the indications for APAL dissection were limited. Patients with lower thoracic esophageal cancer who are suspected to have perigastric lymph node metastasis and APAL micrometastases may be considered for APAL dissection.

Topics: Adult; Aged; Antigens, Neoplasm; Aorta, Abdominal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Serpins

The establishment of esophageal cancer cell lines can facilitate the search for molecular mechanisms underlying its pathogenesis. Two novel human esophageal squamous cell carcinoma (ESCC) cell lines, HKESC-2 and HKESC-3, were established from a moderately differentiated ESCC of a 46-year-old Chinese woman and a well-differentiated ESCC of a 74-year-old Chinese man, both from Hong Kong. The pathological characteristics (morphological, immunohistochemical, and electron microscopic studies), tumorigenicity in nude mice, cytogenetic features, and DNA ploidy of the two cell lines were investigated. The two cell lines have been maintained in vitro for more than 17 months and passaged over 85 times for HKESC-2 and 58 times for HKESC-3. Both grew as monolayers, with a doubling time of 24 hours for HKESC-2 and 48 h for HKESC-3. Their squamous epithelial nature was authenticated by their strong immunopositivity with the anti-cytokeratin antibodies and the ultrastructural demonstration of tonofilaments and desmosomes. They are tumorigenic in nude mice and had DNA aneuploidy. G-banding cytogenetic analysis showed hyperdiploidy in HKESC-2 and near-tetraploidy in HKESC-3. Frequent breakpoints were noted at 1p22, 1p32, and 9q34 in HKESC-2 and at 1p31, 3p25, 3p14, 6q16, 6q21, 8p21, 9q34, 13q32, and 17q25 in HKESC-3. Comparative genomic hybridization analysis found that chromosomal gains were at 3q24-qter, 5q21-qter, 8q11-qter, 13q21-q31, 17q11-qter, 19, 22q22 for HKESC-2 and at 3q13-qter, 5p, 6p, 9q21-qter, 10q21-q22, 12q15-pter, 14q24-qter, 16, 17q24-qter, 20 for HKESC-3. Chromosomal losses were at 3p13-pter, 18q12-qter for HKESC-3. These two newly established cell lines will be useful tools in the study of the molecular pathogenesis and biological behavior of ESCC cells and for testing new therapeutic reagents for ESCC in the future.

Topics: Aged; Aneuploidy; Animals; Asian People; Carcinoma, Squamous Cell; Cell Division; Chromosomes, Human; Esophageal Neoplasms; Female; Hong Kong; Humans; Karyotyping; Keratins; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Proteins; Neoplasm Transplantation; Nucleic Acid Hybridization; Transplantation, Heterologous; Tumor Cells, Cultured

Adenocarcinomas of the esophagogastric junction form a heterogeneous group of tumors. We aimed to evaluate the value of the expression pattern of cytokeratins 7, 19, and 20 for their diagnosis and classification. A total of 85 cases of adenocarcinoma of the distal esophagus and 67 cases of adenocarcinoma of the proximal stomach, defined on strict topographical criteria, were investigated. About 90% of the adenocarcinomas of distal esophagus were positive for cytokeratins 7 and 19, in contrast to <45% of the adenocarcinomas of proximal stomach (p <0.01); 17.6% of the adenocarcinomas of the distal esophagus and 55.2% of the adenocarcinomas of the proximal stomach expressed cytokeratin 20 (p <0.01); and 74.1% of the adenocarcinomas of the distal esophagus and 23.8% of the adenocarcinomas of the proximal stomach had a CK7+/CK20- immunophenotype (p <0.01). In intestinal-type tumors a CK7+/CK20- immunophenotype had a sensitivity of 76.5%, a specificity of 84.5%, and a predictive positive value of 87.3% for the diagnosis of adenocarcinoma of the distal esophagus. Cytokeratin patterns are different in adenocarcinomas of the distal esophagus and in adenocarcinomas of the proximal stomach. A CK7+/CK20- pattern is highly suggestive of an esophageal origin and may be helpful for the correct classification of esophagogastric adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Predictive Value of Tests; Sensitivity and Specificity; Stomach Neoplasms

Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining.. Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin-eosin staining.. CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (-) (P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (-) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (-) ones (5-year survival: 78% vs 56%, P = 0.1860).. Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.

Topics: Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Prognosis

Certain tumors of the esophagus that display both sarcomatous and carcinomatous features have long been recognized. The nomenclature, classification, and histogenesis remain controversial and the microscopic differential diagnosis from other esophageal malignancies can be challenging, particularly in small biopsies. In this paper, we review the literature of carcinosarcoma and present two cases of esophageal carcinosarcoma, describing their salient histologic, immunohistochemical, and ultrastructural features. Also, we assess the expression of MDM2 and CDK4 in the carcinomatous and sarcomatous compartments of our cases and we compare them with the expression of these oncogenes in selected cases of esophageal squamous cell carcinoma with prominent stromal reaction. In both of our cases, identification of some epithelial ultrastructural and immunohistochemical features in cells of otherwise sarcomatous phenotype lends support to the common epithelial origin of these neoplasms. Moreover, positive staining for MDM2 and CDK4 in our cases with equally strong reactions in both carcinomatous and sarcomatous elements provides evidence of a role for these molecules in the pathogenesis of carcinosarcoma. In contrast, in cases of squamous cell carcinoma with prominent stromal reaction only the epithelial cells stained strongly for MDM2 and CDK4. These differences in the MDM2 and CDK4 immunohistochemical profile between carcinosarcomas and carcinomas of the esophagus may assist in their differential diagnosis.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Esophageal Neoplasms; Female; Humans; Keratins; Middle Aged; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2

To study the relationship between the overexpression of CYFRA21-1 in the serum of laryngeal cracinoma patients and the associated clinical feature.. The serum level of CYFRA21-1 were determined by ELISA in 25 laryngeal carcinoma patients preoperatively and postoperatively. 20 laryngeal benign diseases are as control group.. Positive rate was 60% for serum of CYFRA21-1 in the laryngeal carcinoma patiens. The mean serum level for CYFRA21-1 in laryngeal carcinoma patients preoperatively (5.14 +/- 1.82) micrograms/L was significantly elevated than in control group (2.17 +/- 0.68 micrograms/L). The Serum level of CYFRA21-1 1 were significantly declined after surgery under normal level. Serum level of CYFRA21-1 went up once ogain in 2 recurrence patients. There was no correlation between serum level of CYFRA21-1 with age, sex and site in the laryngeal carcinoma patients. There were correlations between the serum level of CYFRA21-1 with clinical stage, pathological grading and lymphatic matatasis. Level of CYFRA21-1 was higher in poorly differentiated.. The study suggests that serem CYFRA21-1 level could be a useful tumor marker for diagnosis, progenosis and follow-up after surgery in laryngeal carcinomas.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Prognosis

A case of esophageal basaloid carcinoma with marked myoepithelial differentiation in a 60-year-old man is reported. The tumor arose as an exophytic mass, measuring 65 x 60 mm, in the middle thoracic esophagus. Approximately two-thirds of the tumor surface was covered with non-cancerous esophageal epithelium. The depth of tumor invasion was limited to the submucosal layer. Histologically, about 70% of the tumor contained a typical basaloid carcinoma component and about 30% contained glandular and intercalated duct-like components with distinct epithelial and myoepithelial differentiation. The tumor presented no component of distinct squamous cell carcinoma, but a small portion of cribriform-like structure, which is typical of adenoid cystic carcinoma, was visible. The inner epithelium composing the intercalated duct-like structure showed immunohistochemical positivity for cytokeratin 14, and the outer epithelium lining adjacent to the stroma showed positivity for alpha-smooth muscle actin. These findings supported epithelial/myoepithelial differentiation. To our knowledge, our case is the first patient with an esophageal basaloid carcinoma showing marked myoepithelial differentiation.

Topics: Actins; Biomarkers, Tumor; Carcinoma, Transitional Cell; Cell Transformation, Neoplastic; Esophageal Neoplasms; Humans; Keratin-14; Keratins; Male; Middle Aged; Myoepithelioma; Neoplasm Staging; Treatment Outcome

Adenocarcinoma of the esophagus (ADCE) with Barrett's mucosa and adenocarcinoma of the cardia (ADCC) are often reported as a single pathological entity. In this study we have used strict anatomical-pathological criteria to distinguish between these two lesions and we have investigated their differences in TP53 mutations, MDM2 gene amplification, and cytokeratin expression. DNA was extracted from the tumor areas of formalin-fixed, paraffin-embedded sections in 26 ADCC and 28 ADCE patients. TP53 mutations were detected by temporal temperature gradient electrophoresis and identified by sequencing. MDM2 amplification was assessed by differential polymerase chain reaction. The expression of cytokeratins 4, 7, and 13 was examined by immunohistochemistry. In ADCC, the male to female ratio was 1.8:1, compared to 27:1 in ADCE. Five ADCC patients had a history of other neoplasms, compared to only one ADCE patient. The two types of tumor differed in the prevalence of TP53 mutations (31% in ADCC and 50% in ADCE) and of MDM2 gene amplification (19% in ADCC and 4% in ADCE), and in the pattern of expression of cytokeratin 7 (positive in 100% of ADCE and in 41% of ADCC) and cytokeratin 13 (positive in 81% of ADCE and in 36.5% of ADCC). ADCE and ADCC differ in their clinical characteristics, in the prevalence of TP53 mutations and MDM2 amplifications, and in the patterns of cytokeratin expression. These results support the notion that ADCC and ADCE are distinct pathological entities.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cardia; Diagnosis, Differential; Esophageal Neoplasms; Female; Gastric Mucosa; Gene Amplification; Gene Expression Regulation, Neoplastic; Humans; Keratin-7; Keratins; Male; Middle Aged; Mutation; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Stomach Neoplasms; Tumor Suppressor Protein p53

The long-term prognosis after surgical therapy for esophageal carcinoma depends on tumor stage and completeness of resection. Similarly to other epithelial tumors, the presence of micro deposits of neoplastic cells in the bone marrow may indicate residual disease and the potential for recurrence. This study assesses the prevalence of bone marrow-disseminated tumor cells in patients undergoing surgical resection for esophageal carcinoma. In addition, we investigated the agreement between immunohistochemical and molecular techniques for the detection of micrometastases in a subgroup of patients.. Between January 1998 and November 1999, forty-eight patients with adenocarcinoma of the esophagogastric junction (n = 29) or squamous cell carcinoma of the thoracic esophagus (n = 19) and no evidence of overt metastatic disease entered the study. An immunohistochemical assay (capable of detecting 1 carcinoma cell in 7 x 10(5) bone marrow cells) was used to test bone marrow obtained by flushing a resected rib or by needle aspiration either of the iliac crest or of a rib. A polymerase chain reaction (PCR) molecular technique was also used to identify bone marrow and peripheral blood epithelial cells.. Cytokeratin-positive cells were found in 79.1% of the bone marrow samples obtained from the rib, and in only 8% of the needle aspirates either from the iliac crest or from a contiguous rib: This difference is probably explained by the improved removal of metastatic cells with the flushing of the rib. Comparable results were obtained at a qualitative level by the PCR technique on bone marrow. In addition, PCR-positive results were found in 3 of 18 peripheral blood samples. There was no association with tumor type, neoadjuvant therapy, or lymph node status. Patients with a pT3 or pT4 tumor showed, at a borderline statistical level, a higher proportion of cytokeratin-positive cells in the flushed rib.. Bone marrow-disseminated tumor cells are present in the resected rib of a high proportion of patients undergoing esophagectomy for carcinoma, and immunohistochemistry seems to be the method of choice for their quantitative assessment. However, the prognostic and therapeutic implications of this finding need further investigation.

Topics: Adenocarcinoma; Adult; Aged; Base Sequence; Bone Marrow Examination; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Cardia; DNA Primers; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Polymerase Chain Reaction; Prognosis; Stomach Neoplasms

Esophageal carcinoma was observed in an eight-year-old, castrated male, Japanese domestic cat. Histologically, this neoplasm consisted of two different growth patterns, squamous cell carcinoma and adenocarcinoma. The results of immunohistochemical examination supported the fact that the two kinds of neoplastic cells have different characteristics. The tumor was, therefore, diagnosed as adenosquamous carcinoma. Esophageal tumors in the cat are very rare and, if any, neither adenocarcinoma nor adenosquamous carcinoma has been reported up to the present.

Topics: Animals; Carcinoembryonic Antigen; Carcinoma, Adenosquamous; Cat Diseases; Cats; Cell Division; Diagnosis, Differential; Esophageal Neoplasms; Immunohistochemistry; Keratins; Male; Mucous Membrane

Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co-ordinate CK7 and 20 expression in the distinction of Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia.. CK7 and 20 immunostaining was performed on randomly selected surgical resection specimens from patients with Barrett's-related oesophageal adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14) arising in a background of intestinal metaplasia. A CK7+ CK20- immunophenotype was demonstrated in 27 of 30 (90%) patients with Barrett's-related oesophageal adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The sensitivity, specificity and positive predictive value of a CK7+/20- immunophenotype for a diagnosis of Barrett's-related oesophageal adenocarcinoma was 90%, 79%, and 90%, respectively.. A CK7+/20- tumour immunophenotype is associated with Barrett's-related oesophageal adenocarcinoma and may be useful in accurate tumour classification, thus facilitating improving epidemiological evaluation of tumours at the oesophagogastric junction.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Metaplasia; Middle Aged; Observer Variation; Predictive Value of Tests; Sensitivity and Specificity; Stomach Neoplasms

Basaloid-squamous cell carcinoma of the esophagus (BSCC) is an extremely rare tumor. Histologically, this tumor should be differentiated from adenoid cystic carcinoma (ACC) and small cell undifferentiated carcinoma (SCUC). Biologically, this tumor is very aggressive, with a propensity for distant metastasis. We report a 64-year-old male with esophageal BSCC. The patient complained of dysphagia and was found to have a torous lesion in the esophagus on radiological examination. Upper gastrointestinal fiberscopy showed a localized ulcerative type tumor, which was diagnosed as squamous cell carcinoma (SCC) on biopsy. Surgery resulted in curative resection. A histological examination of the resected tumor showed features of BSCC. Immunohistochemical examination demonstrated AE3/1- and CAM 5.2-positive tumor cells, and laminin-positive cells in the periphery of the nests. These data were useful in differentiating this tumor from ACC and SCUC. Six months after surgery, the patient developed hepatic metastases, which were successfully treated by regional chemotherapy via the hepatic artery by using fluorouracil. The patient is currently being followed up at the outpatient clinic and shows no signs of any recurrence.

Topics: Biomarkers; Biomarkers, Tumor; Carcinoma, Basosquamous; Diagnosis, Differential; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Laminin; Male; Middle Aged; Phosphopyruvate Hydratase; S100 Proteins

To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour.. In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells.. The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.

Topics: Actins; Adult; Aged; Cadherins; Carcinoma, Squamous Cell; Clone Cells; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth; Tumor Suppressor Protein p53; Vimentin

We recently encountered a patient with basaloid carcinoma of the esophagus with extensive node involvement. The patient died of hematogenous metastasis 6 months after surgery. The tumor expressed cytokeratin but did not express either Type IV collagen or laminin. Both tumor cells and metastatic lesions in the regional lymph nodes expressed p53, Bcl-2, and Ki-67 proteins, but did not express cyclin D1 proteins.

Topics: Biomarkers, Tumor; Carcinoma, Basosquamous; Collagen Type IV; Esophageal Neoplasms; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Laminin; Male; Middle Aged; Radiography

Few studies have investigated the presence of lymph node micrometastases (MM) in the cervical region of patients with esophageal squamous cell cancer. The present study examines the presence of cervical MM and attempts to determine a way to predict the occurrence and site of such micrometastases. A total of 2203 cervical lymph nodes and 118 mediastinal recurrent nerve nodes obtained from 86 patients with esophageal carcinoma were examined immunohistochemically using cytokeratins. Cervical lymph nodes and mediastinal recurrent nerve nodes metastases were detected histologically in 33 and 41 of the 86 patients respectively. Cervical lymph node and mediastinal recurrent nerve node MM were immunohistochemically detected in 16 (18.6%) and 6 (7.0%) patients respectively. Of these 16 patients with cervical MM, seven were found to have lymph node metastases in different cervical regions, whereas cervical MM only were detected in nine patients. Among the former group of patients, five were diagnosed by ultrasound examination as having cervical lymph node metastases. Mediastinal recurrent nerve node metastases and MM correlated with the presence of cervical MM in all but one patient. Cervical lymph node metastasis, including micrometastasis, can be predicted by preoperative ultrasonography and the routine histologic examination of mediastinal recurrent nerve nodes.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck

Although the sentinel node (SN) concept has been validated in malignant melanoma and breast cancer, the application of this concept for other solid tumors, including gastrointestinal (GI) cancer, is still controversial. We have demonstrated the feasibility of radioguided SN mapping during laparotomy in patients with esophageal, gastric, and colorectal cancers. In 188 patients, the SNs identified by this technique had an overall diagnostic accuracy of 96% for regional lymph node metastasis. Aberrant drainage sites that have been called skip metastasis from the primary lesion were detectable using this method. More recently, we have undertaken SN mapping during laparoscopic surgery. A combination of radiotracer and blue dye optimized the identification of SNs that drained GI cancers. Our preliminary data indicate that laparoscopic mapping of the SN is a sensitive intraoperative technique for identifying lymph node micrometastasis, and we believe that it will become an important component of a minimally invasive approach to early-stage GI cancers.

Topics: Colonic Neoplasms; Coloring Agents; Esophageal Neoplasms; Gastrointestinal Neoplasms; Humans; Keratins; Laparoscopy; Lymphatic Metastasis; Radionuclide Imaging; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Technetium Tc 99m Aggregated Albumin

To explore the biological features of basaloid squamous cell carcinoma (BSC) of the esophagus.. Cytokeratins (CK4, CK18 and CK19), epithelial membrane antigen (EMA), carcino embryo antigen (CEA), alpha-smooth muscle antigen (alpha-SMA), S-100, laminin (LN), collagen IV (Col-IV), neural-specific enolase (NSE), proliferating cell nuclear antigen (PCNA) and p53 antibodies were used to detect the corresponding antigen expression in 8 cases of BSC with ABC immunohistochemical methods.. Two kinds of BSC cell components have different responses to the above antibodies. For basaloid cells (BCs), 7 cases were positive for CK19, and were negative for the other 4 epithelial antibodies CK4, CK18, CEA and EMA. BCs of 4 cases were positive to the muscular antibodies alpha-SMA and S-100, and the hyaline degeneration in the tumor nests was positive for LN and Col-IV. BCs had a high index of PCNA, with an average level of 54%. For squamous cells (SCs), 7 cases were positive for the epithelial antigen CK4, CEA and EMA, but were negative for CK19, alpha-SMA and S-100. The index of PCNA of SC was low, with an average level of 25%.. BSC of the esophagus is a high-malignancy tumor which is of multi-oriented differentiation. BCs represent basal cells which have the tendency of myoepithelial differentiation and have strong proliferation ability, whereas SCs represent typical squamous cell differentiation.

Topics: Carcinoembryonic Antigen; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Mucin-1; Proliferating Cell Nuclear Antigen; S100 Proteins

Cyfra 21-1 is a useful marker in lung cancer. The only tumor marker used at the present time in oesophageal squamous cell carcinoma (OSCC) is SCC (squamous cell carcinoma). In this study we evaluated the pre-treatment sensitivity and specificity of these two markers in this setting. Cyfra 21-1 and SCC were determined by radio-immunoassay on 76 patients having OSCC. Staging was done according to the UICC 1978 classification based on endoscopy, baryum enema and CT scan. The sensitivity of Cyfra 21-1 is better at the 1.5 ng/ml level (54%) than at the usual reported level of 3.6 ng/ml (26%). The best level for sensitivity of SCC is 1.5 ng/ml. At these levels, sensitivity of Cyfra 21-1 and SCC for advanced stages (T3 or M1) are respectively 72% and 50%. The specificity of Cyfra 21-1 and SCC for stages T1 or T2 are respectively 53% and 73%. The combination of these two markers increase sensitivity at 64% for all stages and at 89% for advanced stages (T3 or M1) and is a significant prognostic factor for survival. This study confirms the value of Cyfra 21-1 in OSCC at the normal level of 1.5 ng/ml. The combination with SC improves the results. We now need to evaluate the role of these two markers in the follow up of oesophageal carcinoma.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Sensitivity and Specificity; Serpins

p63 is a p53-related DNA-binding protein that helps regulate differentiation and proliferation in epithelial progenitor cells. Its expression has never been evaluated in the human gastrointestinal tract. The aim of this study was to evaluate the expression of p63 in the esophagus and related metaplastic and neoplastic disorders to gain insight into the pathogenesis of these processes. Of particular interest was the expression of p63 in Barrett esophagus (BE) and in BE-associated multilayered epithelium. Multilayered epithelium has been postulated to represent an early precursor to the development of BE primarily because it shares morphologic and immunophenotypic features of both squamous and columnar epithelium, and has been shown prospectively to be highly associated with BE. Routinely processed mucosal biopsy or resection specimens that contained normal esophageal squamous epithelium (n = 20), squamous dysplasia (n = 4), squamous cell carcinoma (n = 7), BE (n = 10), BE-associated multilayered epithelium (n = 13), esophageal mucosal gland ducts (n = 10), BE-associated dysplasia (n = 12), and BE-associated adenocarcinoma (n = 7) were immunostained for p63 to determine the extent and location of staining. p63 staining was compared with the staining patterns observed for p53, Ki 67 (proliferation marker), and cytokeratins (CKs) 13 (squamous marker), 14 (basal squamous marker), 8/18 (columnar marker), and 19 (basal/columnar marker). Expression of p63 messenger RNA (mRNA) isoforms was also analyzed by reverse-transcription polymerase chain reaction of freshly isolated tissues. In the normal esophagus, p63 was expressed in the basal and suprabasal layers of the squamous epithelium and in basal cells that line the mucosal gland ducts but was negative in all other epithelia of the gastrointestinal tract, including the stomach, small intestine, and colon. Similarly, p63 was not expressed in BE, but it, was present in the basal layer of multilayered epithelium in 9 of 13 cases (69%). p63-positive cells in multilayered epithelium and in the mucosal gland duct epithelium were positive for CK8/18 (100%) and CK13 (67% and 30%, respectively) and negative for CK14 (0%), in contrast to p63-positive cells in squamous epithelium, which were positive for CK14 and CK13 (100%) but negative for CK8/18. In neoplastic tissues, p63 was diffusely expressed in all cases of esophageal squamous cell dysplasia and carcinoma but was negative in all cases of esophageal and colorectal ad

Topics: Adenocarcinoma; Barrett Esophagus; Carcinoma, Squamous Cell; Digestive System; DNA-Binding Proteins; Epithelium; Esophageal Diseases; Esophageal Neoplasms; Esophagus; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Metaplasia; Phosphoproteins; Protein Isoforms; Retrospective Studies; RNA, Messenger; Trans-Activators; Transcription Factors; Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

To study the clinical significance of the novel tumor marker--CYFRA21-1 in patients with esophageal cancer.. The CYFRA21-1 level in serum of 84 patients with a definite diagnosis of esophageal cancer was examined 10 days before and after operation by ELISA. A 3 years' follow-up was conducted to the survival of patients.. (1) The CYFRA21-1 level was > 3.3 ng/ml in 72.6% of the patients (61/84). (2) The serum CYFRA21-1 level decreased significantly after operation in patients at stage III or with high differentiation (P < 0.05). (3) The difference between pre- and post-operative serum CYFRA21-1 levels was statistically significant in patients who had undegone radical operation, and was not in patients who had undergone palliative operation. (4) In addition to stage (P < 0.05) and type of operation (P < 0.05), the difference of CYFRA21-1 level before and after operationwas closely related to the prognosis (P < 0.05).. CYFRA21-1 is a useful marker in diagnosis and prediction of prognosis of esophageal cancer.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Logistic Models; Male; Middle Aged; Palliative Care; Prognosis; Software; Survival Analysis

A pleomorphic (giant cell) carcinoma of the esophagus is reported in a 52-year-old man who had dysphagia and weakness. The 8-cm-high vegetating tumor consisted of solid sheets of poorly cohesive epithelioid cells broken into clusters by strands of stroma. Numerous giant cells showing phagocytic phenomenon were present. Immunochemical analyses demonstrated the epithelial origin of the neoplasm, although most of the tumor cells strongly expressed vimentin. Numerous tumor cells expressed synaptophysin. Neurosecretory granules were detected in some tumor cells on electron microscopic examination. The patient died 4 months after he became symptomatic. As far as we can ascertain, this is the first case report describing a pleomorphic carcinoma arising in the esophagus. This poorly differentiated carcinoma might be of neuroendocrine differentiation. In the esophagus, pleomorphic carcinoma must be distinguished from polypoid tumors such as carcinosarcoma and malignant melanoma.

Topics: Biomarkers, Tumor; Carcinoma, Giant Cell; Cytoplasmic Granules; Esophageal Neoplasms; Fatal Outcome; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Male; Middle Aged; Neurosecretory Systems; Synaptophysin; Vimentin

We examined the prevalence, patterns, and clinical significance of nodal micrometastases in patients with esophageal cancer.. Cervical, mediastinal, and abdominal lymph nodes systematically removed from 37 patients without conventional histologic evidence of lymph node metastasis from esophageal squamous cell carcinoma were immunohistochemically examined to detect cells that were stained for cytokeratins by the monoclonal antibody cocktail AE1/AE3. Postoperative care and survival were compared in cases with and without such micrometastases.. Nodal micrometastases were found in 14 of 37 patients (38%). Among these patients, 9, 7, and 4 had micrometastases to abdominal, mediastinal, and cervical lymph nodes, respectively. Postoperative tumor recurrence was significantly more frequent in patients with micrometastases (50%) than in those without (9%, P = .008). Overall and relapse-free survival in the former group was significantly worse than in the latter group (P = .042 and P = .002, respectively). Nodal micrometastases had an independent prognostic importance for relapse-free survival as determined by multivariate analysis.. Metastatic tumor cells are frequently present in lymph nodes, even in patients without histologic evidence of nodal metastasis from esophageal cancer. Nodal micrometastases indicates a poorer prognosis after a curative esophagectomy procedure in histologically node-negative cases.

Topics: Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Survival Analysis

In the normal stratified squamous epithelium of the esophagus, only the third to the fifth layers of cells express the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). Using immunohistochemical staining, we examined the topological distribution of cells expressing p21, p53, Ki67, and cytokeratin 10 (CK10), a differentiation marker of esophageal squamous cell carcinoma (SCC), in 25 superficial SCCs and 72 dysplastic lesions of the esophagus. Image analysis of p21, p53, and Ki67 expression was also performed in 48 dysplastic lesions. In superficial SCCs, although Ki67- and p53-expressing cells were mainly distributed in the deep layers of tumors despite tumor differentiation, the distribution of p21 correlated with tumor differentiation. In dysplastic lesions, p53- and Ki67-coexpressing cells tended to locate in the same layers and expand in the lower layers of epithelium with the progression of dysplasia. p21-expressing cells shifted to the upper layers of the epithelium with the progression of dysplasia. However, this change was heterogeneous; in some lesions, p21-expressing cells were confined to the superficial layers of atypical cells (confined type), whereas in others, p21-overexpressing cells were scattered among atypical cells (scattered type). CK10 expression was observed in 25% of dysplastic lesions, and the frequency of CK10 expression was significantly higher in the scattered than in the confined type. Our results suggest that esophageal squamous dysplasia represents the earliest pathological process in esophageal squamous carcinogenesis. Our results also suggest that differentiation of esophageal SCC is determined at the stage of dysplasia, and that p21 plays a critical role in the differentiation process.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Enzyme Inhibitors; Epithelium; Esophageal Neoplasms; Esophagus; Female; Humans; Keratin-10; Keratins; Male; Middle Aged; Precancerous Conditions; Tumor Suppressor Protein p53

The ets family of transcription factors comprises many members which contribute to diverse cellular functions that vary depending upon the cell- and tissue-type context. Recently, different groups have identified a novel member of the ets family that is epithelial-specific. Variably called ESE-1, ERT, jen, ESX, this gene is designated currently as ELF3. In order to understand transcriptional regulatory mechanisms mediated by ELF3, we investigated its effect on the human keratin 4 gene promoter based upon the role of keratin 4 in early differentiation of the esophageal squamous epithelium. Interestingly, ELF3 suppressed basal keratin 4 promoter activity in both esophageal and cervical epithelial cancer cell lines, a novel result, while simultaneously activating the late-differentiation linked SPRR2A promoter. Furthermore, serial deletion constructs of the keratin 4 promoter continued to be suppressed by ELF3, a phenomenon that was only partially rescued by ELF3 ets domain mutants, but completely abrogated by deletion of the ELF3 pointed domain. These results suggest that ELF3 may have dual functions in the transcriptional regulation of genes involved in squamous epithelial differentiation. One of these functions may not be exclusively mediated through DNA binding in the context of transcriptional suppression of the keratin 4 promoter.

Topics: Amino Acid Sequence; Carcinoma, Squamous Cell; Cell Differentiation; DNA-Binding Proteins; Epithelial Cells; Esophageal Neoplasms; HeLa Cells; Humans; Keratins; Molecular Sequence Data; Mutation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ets; Transcription Factors; Tumor Cells, Cultured

The telomere and the telomerase in human esophageal cancer are not yet completely understood. The regulatory mechanism of telomerase activity and telomere dynamics has drawn considerable attention. It is generally assumed that when telomerase has been activated, no further telomere shortening should ensue; however, a much more complex pattern of telomere dynamics may exist in telomerase-positive cancer cells. A novel human esophageal cancer cell line (KAN-ES) was established and characterized. Using KAN-ES and its serially passaged subclones up to the 55th generation, we determined the alteration of telomere length (TRF), telomerase activity (TA), telomerase RNA expression (hTR), population doubling time, karyotype, and cytokeratin 14 expression during the process of establishing a cancer cell line. We found that the TRF was maintained between 4.0 and 5.0 kb during the serial passages, despite sustained high TA (assessed by an in vitro TRAP assay). No close relationships were found among TRF, TA, and hTR expression. TA and telomere dynamics were not associated with cellular growth ability and differentiation. However, the number of population doublings showed significant correlations with both the TA and doubling times. In conclusion, these dissociations between telomere dynamics and TA support the existence of additional controls on TRF in cancer cells. KAN-ES and its restored subclones should prove a valuable resource for esophageal cancer research.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Division; Cell Transformation, Neoplastic; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Keratins; Male; Middle Aged; RNA, Messenger; Telomerase; Telomere; Tumor Cells, Cultured

The detection of epithelial cells in bone marrow, blood or lymph nodes indicates a disseminatory potential of solid tumours. 225 patients with squamous cell carcinoma of the oesophagus were prospectively studied. Prior to any therapy, cytokeratin-positive (CK) cells in bone marrow were immunocytochemically detected in 75 patients with the monoclonal anti-epithelial-cell antibody A45-B/B3 and correlated with established histopathologic and patient-specific prognosis factors. The prognosis factors were assessed by multivariate analysis. Twenty-nine of 75 (38.7%) patients with oesophageal cancer showed CK-positive cells in bone marrow. The analyses of the mean and median overall survival time showed a significant difference between patients with and without epithelial cells in bone marrow (P < 0.001). Multivariate analysis in the total patient population and in patients with curative resection of the primary tumour confirmed the curative resection rate and the bone marrow status as the strongest independent prognostic factors, besides the T-category. The detection of epithelial cells in bone marrow of oesophageal cancer patients is a substantial prognostic factor proved by multivariate analysis and is helpful for exact preoperative staging, as well as monitoring of neoadjuvant therapy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Bone Marrow; Bone Marrow Examination; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Epithelial Cells; Esophageal Neoplasms; Esophagectomy; Female; Fluorouracil; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Stem Cells; Prognosis; Prospective Studies; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome

A rare case of carcinoma characterized by extensive chondroid elements at a site of primary esophageal and metastatic lesion is reported. The patient was a 67-year-old man complaining of dysphagia due to an ulcerative lesion at the lower middle esophagus. He underwent irradiation treatment prior to surgery. Histologically, the tumor consisted of both carcinomatous and chondroid elements and had invaded deeply into the esophageal wall. The carcinomatous cells had gradually become chondroid cells embedded within an extensive extracellular matrix. In addition, the metastatic lesion showed findings similar to those of the primary lesion. Immunohistochemistry revealed that both carcinomatous and chondroid elements were immunostained with cytokeratin and epithelial membrane antigen, suggesting an epithelial nature to the chondroid cells. Conversely, only chondroid cells were positively stained for S-100 protein. Furthermore, bone morphogenetic proteins (BMP) were positive for chondroid cells and their surrounding carcinomatous cells. Given the apparent transition between carcinomatous and chondroid cells based on microscopy and immunohistochemical findings in the present case, we concluded that the chondroid cells were derived from carcinomatous cells. In addition, our findings suggest that BMP produced by carcinomatous cells lead to chondroid differentiation of the carcinoma cells.

Topics: Aged; Bone Morphogenetic Proteins; Carcinoma, Squamous Cell; Cell Differentiation; Chondrocytes; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Mucin-1; S100 Proteins

While there are reports that CYFRA 21-1 is a useful tumor marker, to our knowledge the clinical utility of this marker to detect recurrences for squamous cell carcinoma of the esophagus has not been addressed.. By immunoradiometric assay, human serum levels of CYFRA 21-1, SCC antigen and CEA were measured in esophageal squamous cell carcinoma patients prior to their initial treatment. Monthly follow-ups of these tumor markers was done after surgery.. The diagnostic sensitivity of CYFRA 21-1 was 43.9% (18 of 41), a value superior to that for SCC antigen (26.8%) and CEA (17.0%) (P < 0.05). The positive rates of CYFRA 21-1 increased with progression of the disease, 22.2% of pTNM Stage 0-IIA and 77.8% of pTNM Stage IIB/III (P = 0.013), whereas SCC antigen and CEA rates were not related to pTNM stage. Among 13 patients with clinical evidence of a recurrence, 76.9% (10 of 13) exhibited an increase in CYFRA 21-1, and this increase was evident before clinical detection of the recurrence in 9 of these 13 patients (69.2%). Consequently, postoperative elevations of serum CYFRA 21-1 levels were indicative of a tumor recurrence 1-13 months before acquisition of clinical and radiological data.. The assay of CYFRA 21-1 is useful not only for diagnosis but also for close monitoring of patients with esophageal squamous cell carcinoma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Keratin-19; Keratins; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Sensitivity and Specificity

Metastatic signet ring cell carcinomas of unknown primary site can represent a clinical problem. Gastrointestinal signet ring cell carcinomas and invasive lobular carcinomas of the breast are the most common sources of these metastases. Immunohistochemical algorithms have been successfully used in the search for the unknown primary adenocarcinomas. In the present study a series of primary invasive lobular breast carcinomas (79 cases) and their metastases and a series of gastrointestinal signet ring cell carcinomas (22 primary and 13 metastases) were stained with monoclonal antibodies for cytokeratin (CK) 20 and CK7 and for estrogen receptors (ER). The staining was evaluated as negative (no staining), focally (less than 10% of the tumor cells stained) or diffusely positive. All the primary and metastatic gastrointestinal signet ring cell carcinomas proved to be CK20 positive, while only 2/79 (3%) of the primary and 1/21 metastatic lobular carcinomas (5%) stained positively for this CK. None of the gastrointestinal carcinomas and the majority of the lobular carcinomas expressed ER. The majority of the tumors were CK7+. Using CK20 alone, 33 of 34 metastases could be properly classified as gastrointestinal (CK20+) or mammary (CK20-). ER identified 31/34 of breast cancer metastases. By combining the results of CK20 and ER staining all the metastases could be properly classified as the CK20+/ER- pattern identified all the gastrointestinal tumors.

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoma, Signet Ring Cell; Colorectal Neoplasms; Diagnosis, Differential; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms, Unknown Primary; Receptors, Estrogen; Stomach Neoplasms

Patients with superficial (mucosal or submucosal) esophageal carcinoma (SEC) have significantly better survival rates than patients with advanced carcinoma. Some patients with advanced esophageal carcinoma have been reported to test positive for serum p53 antibodies (Abs). Because very few patients with superficial carcinoma have been examined, the aim of this study was to evaluate the clinical significance of serum p53-Abs in patients with superficial esophageal squamous cell carcinoma (SESCC).. Thirty-five consecutive patients with SESCC were studied for serum p53-Abs by enzyme-linked immunoabsorbent assay before and after treatment. The clinicopathologic features of p53 seropositive and p53 negative patients were compared. The relation between the presence of serum p53-Abs and p53 immunoreactivity of the resected specimens was examined. Three tumor markers (squamous cell carcinoma antigen [SCC-Ag], CYFRA21-1, and carcinoembryonic antigen [CEA]) were assessed to compare their sensitivities with serum p53-Abs.. Fourteen of 35 patients (40%) were p53 seropositive. Relatively few patients tested positive for the other tumor markers: CEA, 11.4%; SCC-Ag, 14.3%; CYFRA21-1, 5.7%. There were no significant correlations between clinicopathologic features and p53 seropositivity except for tumor location. A strong correlation between p53 immunostaining and the presence of serum p53-Abs was observed (P = 0.003). Of the 14 patients with seropositive results, 12 turned seronegative after resection, and the other 2 experienced disease recurrence.. Surveillance of serum p53-Abs is superior to the three tumor markers for detecting SESCC. This serum marker is also useful for the detection of p53 protein overexpression and for the monitoring of residual tumor cells.

Topics: Aged; Antibodies, Neoplasm; Antigens, Neoplasm; Autoantibodies; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Survival Rate; Tumor Suppressor Protein p53

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.

Topics: Actins; Adenocarcinoma; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Differentiation; Chromogranins; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Muscle, Smooth

This study was conducted to determine a potential use of CYFRA 21-1 in patients suffering from carcinoma of the esophagus. CYFRA 21-1 serum concentrations of 50 patients with histologically proven malignant lesion of the esophagus were compared with 50 healthy persons, 50 patients with benign esophageal disease, and 50 patients with benign lung disease. Additional analysis of serum carcinoembryonic antigen, CA 72-4, and squamous cell carcinoma-antigen serum concentrations were performed. The patients with esophageal carcinoma underwent follow-up tumor marker examinations every three months for 1 year. Analysis to detect statistically significant differences was conducted to estimate a cutoff and to evaluate tumor entity, tumor stage, survival, and tumor-free survival. CYFRA 21-1 at a cutoff of 1.40 ng/ml showed an overall sensitivity to esophageal carcinoma of 36% (45.5% to squamous cell carcinoma, 17.6% to adenocarcinoma) at a specificity of 97.3%. CYFRA 21-1 concentrations showed a tendency to higher serum levels depending on local tumor burden. A correlation of CYFRA 21-1 with various N- or M-stage disease was not observed. Postoperative development in terms of survival and tumor-free survival showed significant correlation to preoperative CYFRA 21-1 concentrations. Clinical tumor recurrence was preceded by CY-FRA 21-1 elevation by 3.4 months. For prognosis and follow-up, this marker is justified for additional analysis in a larger series of patients suffering from carcinoma of the esophagus.

Topics: Adult; Aged; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Serpins

Reverse transcriptase polymerase chain reaction (RT-PCR) is often used for sensitive detection of micrometastasis in peripheral blood, lymph nodes and bone marrow. While the utility of this method has been documented, it also has limitations in the detection of micrometastasis. The mRNA of target genes can be detected in healthy donors or in samples used for negative control, therefore the non-quantitativeness of conventional RT-PCR has been called into question. We analyzed the expression level of cytokeratin (CK) 18 mRNA in established esophageal and gastrointestinal carcinoma cell lines and non-epithelial cells, using quantitative RT-PCR, based on real time 'TaqMan TM' technology. CK 18 mRNA is more highly expressed in carcinoma cells than in non-epithelial cells. However, the expression level in non-epithelial cells was easily detected using conventional RT-PCR and agarose gel electrophoresis. In an analysis of CK 18 mRNA expression in peripheral venous blood in 13 healthy volunteers, we found that CK 18 mRNA was much less expressed than in cancer cell lines. However, the expression in all samples was at a level which was also detected using conventional RT-PCR. It would thus seem that not only qualitative, but also quantitative analysis, of the target mRNA is important to detect micrometastasis. Quantitative RT-PCR methods will make comparisons of the possible differences in expression levels of the target gene. For clinical applications, much further study is needed.

Topics: Adult; Colorectal Neoplasms; DNA Primers; Electrophoresis, Agar Gel; Esophageal Neoplasms; Genetic Vectors; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Keratins; Lung Neoplasms; Male; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Stomach Neoplasms; Transcription, Genetic; Tumor Cells, Cultured

Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity.. In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18-positive cells. Viability and tumorigenicity were determined by culture and xenograft.. Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice.. Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

Topics: Adenocarcinoma; Animals; Bone Marrow; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagogastric Junction; Flow Cytometry; Humans; Ilium; Keratins; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Staging; Prospective Studies; Ribs; Stomach Neoplasms; Transplantation, Heterologous

Lymph node metastasis is a well known feature of poor prognosis in patients with esophageal adenocarcinoma and squamous cell carcinoma. However, a significant proportion of apparently lymph node negative patients die early of metastatic disease. The aim of this study was to determine the prevalence and prognostic significance of occult lymph node metastasis in patients with esophageal adenocarcinoma and squamous cell carcinoma.. Lymph node sections from esophagectomy specimens of 78 patients with lymph node negative esophageal carcinoma (49 patients with adenocarcinoma and 29 with squamous cell carcinoma) were cut serially, it toto, and immunostained with the cytokeratin antibody AE1/AE3 and evaluated for occult lymph node metastasis. The results were correlated with the clinical and pathologic features and with patient survival.. Fifteen of 49 patients (31%) with adenocarcinoma and 5 of 29 patients (17%) with squamous cell carcinoma had occult lymph node metastasis detected by cytokeratin staining. In the adenocarcinoma patients, the presence of occult lymph node metastasis showed a significant correlation with increasing depth of invasion, but was not associated significantly with any other clinical or pathologic feature. In the squamous cell carcinoma patients, the presence of occult lymph node metastasis did not correlate significantly with any clinical or pathologic parameter, except that patients with occult lymph node metastasis were more likely to have received preoperative chemotherapy or radiation therapy. Occult lymph node metastasis did not correlate with poorer survival rates in patients with either adenocarcinoma (Cox proportional hazards ratio: 1.42; P - 0.46) or squamous cell carcinoma (Cox proportional hazards ratio: 0.86; P = 0.90).. Occult lymph node metastasis is not an independent poor prognostic feature in esophageal adenocarcinoma or squamous cell carcinoma. Therefore, the authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostication of patients with these malignancies.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Proportional Hazards Models

A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a congenital anomaly. The present case concerns a 79-year-old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions. Histological examination of these glands, all of which were located in the lamina propria, revealed lobules of cells that showed characteristic sebaceous differentiation. Bulbous nests of proliferating basal cells showing sebaceous differentiation were occasionally observed in the esophageal epithelium. Of the antibodies against six different keratins used, only anti-keratin 14 labeled both the heterotopic sebaceous glands and the bulbous nests. Acquired metaplastic change of the esophageal epithelium is probably the pathogenetic mechanism involved in these unusual lesions.

Topics: Aged; Carcinoma, Squamous Cell; Choristoma; Esophageal Diseases; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratin-14; Keratins; Male; Metaplasia; Sebaceous Glands

To determine the clinical efficacy of serum concentration of cytokeratin 19 fragment (CYFRA 21-1), sera from 66 patients with oesophageal squamous cell carcinoma were examined, and 54 surgically resected specimens were immunohistochemically stained for cytokeratin 19 (CK-19). The patients with positive CK-19 staining in the tissues of their carcinomas had significantly higher serum CYFRA 21-1 levels compared with those with negative CK-19 staining. When the cut-off value was defined as 2.0 ng/mL, CYFRA 21-1 had a higher positive ratio than that of either squamous cell carcinoma antigen (SCC-Ag) or carcinoembryonic antigen (CEA). Serum CYFRA 21-1 level increased significantly along with the clinical stages. In addition, serum CYFRA 21-1 level served as a prognostic factor for patients with oesophageal carcinoma after surgery, whilst SSC-Ag and CEA is not connected with the outcome. These findings suggest that the serum CYFRA 21-1 probably originated from the tumour tissue is an important marker for determining the stage and outcome of oesophageal carcinoma.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Serpins

Lymph node metastasis is a strong independent prognostic factor for oesophageal cancer. The expression of matrix metalloproteinases (MMPs) and reduction of E-cadherin correlate with lymph node metastasis of oesophageal cancer. We previously reported that the expression of vascular endothelial growth factor (VEGF) is associated with lymph node metastasis. This study was designed to determine whether VEGF, MMP-9 and E-cadherin expression is stable or changes in the process of lymph node metastasis of oesophageal cancer. Using immunohistochemistry, we detected VEGF, MMP-9 and E-cadherin expression in paraffin-embedded specimens of oesophageal squamous cell carcinoma. We classified 134 primary tumours and 174 nodal metastases using two different criteria: the absence [Group N(-)] or presence [Group N(+)] of nodal metastasis, and the stage of metastasis--Early Stage (cancer cells < 50% of lymph node) or Late Stage (> or = 50%)--and compared the expression among two groups and among two stages. The expression rates of Group N(-), Group N(+), Early Stage and Late Stage are as follows: VEGF (49%, 74%, 60%, 33%), MMP-9 (76%, 65%, 95%, 69%) and E-cadherin (49%, 24%, 55%, 38%). VEGF expression was down-regulated in Late Stage lymph node metastasis, while MMP-9 expression was elevated in Early Stage metastasis. E-cadherin expression is restored somewhat in Early Stage metastasis, but suppressed again in Late Stage metastasis. These data suggest that the expression of VEGF, MMP-9 and E-cadherin each change in the process of lymph node metastasis in oesophageal cancer, and that the patterns of change are different.

Topics: Adult; Aged; Aged, 80 and over; Cadherins; Collagenases; Endothelial Growth Factors; Esophageal Neoplasms; Female; Humans; Keratins; Lymphatic Metastasis; Lymphokines; Male; Matrix Metalloproteinase 9; Middle Aged; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Dissemination of single tumor cells to the bone marrow is a common event in cancer. The clinical significance of cytokeratin-positive cells detected in the bone marrow of cancer patients is still a matter of debate. In gastric cancer, overexpression of the receptor (uPAR or CD87) for the serine protease urokinase-type plasminogen activator (uPA) in disseminated cancer cells indicates shorter survival of cancer patients. A new immunofluorescence approach, applying confocal laser scanning microscopy, is introduced to locate CD87 antigen in cytokeratin-positive tumor cells and to quantify the CD87 antigen by consecutive scanning. At first, cytokeratin 8/18/19-positive carcinoma cells are identified at excitation wavelength 488 nm using monoclonal antibody A45B/B3 to the cytokeratins and goat anti-mouse IgG labeled with the fluorochrome Alexa488. Next, CD87 in tumor cells is identified by chicken antibody HU277 to the uPA-receptor and goat anti-chicken IgY labeled with fluorochrome Alexa568 (excitation wavelength 568 nm) and the fluorescence signal quantified on a single cell basis using fluorescently labeled latex beads as the fluorescence reference. From 16 patients with gastric or esophageal carcinoma, bone marrow aspirates were obtained, stained for cytokeratins and CD87 and then subjected to laser scanning fluorescence microscopy. Three of six gastric cancer patients had tumor cells present in the bone marrow of which 2 stained for CD87. Three of ten esophageal carcinoma patients had tumor cells in the bone marrow, all three samples stained for CD87. CD87-positive tumor cells were also dissected from stained bone marrow aspirates by laser microdissection microscope to allow analysis of single cells at the gene level.

Topics: Adenocarcinoma; Adult; Aged; Bone Marrow Examination; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Fluorescent Antibody Technique, Indirect; Humans; Immunohistochemistry; Keratins; Microscopy, Confocal; Middle Aged; Plasminogen Activators; Predictive Value of Tests; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Sensitivity and Specificity; Stomach Neoplasms; Tumor Cells, Cultured

This study assessed the clinical value of CYFRA 21-1 in comparison with squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112 primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1 were closely correlated with TNM stage and wee below the cutoff value in all 21 patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the cutoff value among the 80 patients who underwent esophagectomy had lymph node metastases (pN1). A correlation was found between CYFRA 21-1 levels and clinical response in serial measurements of 21 patients who received chemotherapy or chemo radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis, but that it is valuable for monitoring the efficacy of therapy.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Male; Middle Aged; Neoplasm Staging; Serpins

Spindle cell squamous esophageal carcinomas are distinctive polypoid "biphasic" tumors in which the sarcoma-like phenotype usually predominates over the epithelial component. To biologically assess both phenotypes, we compared the tumoral proliferative activity and DNA ploidy between the two histological components of 13 polypoid spindle cell squamous carcinomas of the esophagus. We studied the tumoral proliferative index (TPI) using MIB 1 monoclonal antibody (Ki-67) and determined the DNA histogram by image cytometry on Feulgen-stained sections. The DNA histograms were classified into four types (I to IV) according to the degree of dispersion of the DNA. The TPI of the carcinomatous regions ranged from 0.20 to 0.63 (mean, 0.44) and from 0.55 to 0.85 for the sarcoma-like areas (mean, 0.68) P < .0001. In all cases, the sarcoma-like areas were aneuploid, and 37.5% of the carcinomatous regions were diploid. Also, in all instances the carcinomatous areas were of either histogram type I or II, and the sarcoma-like areas showed histograms of type II or III. We conclude that in esophageal spindle cell squamous carcinomas the sarcoma-like phenotype differs biologically in two ways from the carcinomatous: (1) it has a higher TPI and (2) it has higher aneuploidy with a greater dispersion of the DNA content. We postulate that these characteristics could give a "growth" advantage to the sarcoma-like component of these tumors and explain its predominance over the carcinomatous component.

Topics: Aged; Carcinoma, Squamous Cell; Cell Division; DNA, Neoplasm; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Ki-67 Antigen; Male; Middle Aged; Mitotic Index; Ploidies

The stratified squamous epithelium comprises actively proliferating basal cells that undergo a program of differentiation accompanied by morphological, biochemical, and genetic changes. The transcriptional regulatory signals and the genes that orchestrate this switch from proliferation to differentiation can be studied through the keratin gene family. Given the localization of keratin 4 (K4) to the early differentiated suprabasal compartment and having previously demonstrated that targeted disruption of this gene in murine embryonic stem cells results in impairment of the normal differentiation program in esophageal and corneal epithelial cells, we studied the transcriptional regulation of the human K4 promoter. A panel of K4 promoter deletions were found in transient transfection assays to be predominantly active in esophageal and corneal cell lines. A critical cis-regulatory element resides between -163 and -140 bp and contains an inverted CACACCT motif. A site-directed mutated version of this motif within the K4 promoter renders it inactive, whereas the wild-type version is active in a heterologous promoter system. It specifically binds esophageal-specific zinc-dependent transcriptional factors. Our studies demonstrate that regulation of the human K4 promoter is in part mediated through tissue-specific transcriptional factors.

Topics: Animals; Base Sequence; Carcinoma, Squamous Cell; Cell Differentiation; Cell Line; Esophageal Neoplasms; Esophagus; Gene Expression Regulation; HeLa Cells; Humans; Keratins; Mice; Mice, Knockout; Molecular Sequence Data; Multigene Family; Mutagenesis, Site-Directed; Nuclear Proteins; Promoter Regions, Genetic; Recombinant Proteins; TATA Box; Tongue; Transfection; Tumor Cells, Cultured

Retinoids are vitamin A analogs that regulate growth and differentiation of squamous epithelial cells in vitro and in vivo. We examined the effects of retinoic acid (RA) and N-(4-hydroxy-phenyl) retinamide (HPR) on the growth properties of esophageal squamous carcinoma cell lines, and found that both RA and HPR induce morphological changes and inhibit growth. Immunofluorescence studies suggest alterations in keratins as a result of treatment with RA or HPR. In order to determine underlying molecular mechanisms, we found that RA or HPR did not induce arrest of cells in the G1 phase nor did treated cells undergo apoptosis. However, RA and HPR treatment did result in the downregulation of epidermal growth factor receptor (EGFR) which is known to bind key proproliferative ligands, such as epidermal growth factor and transforming growth factor alpha.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Squamous Cell; Cell Division; Cell Size; ErbB Receptors; Esophageal Neoplasms; Fenretinide; Flow Cytometry; Humans; Keratins; Time Factors; Tretinoin; Tumor Cells, Cultured

CYFRA 21-1 measures soluble cytokeratin-19 fragments in serum and is a useful marker for lung carcinoma, especially squamous cell carcinoma (SCC). The authors conducted this study to determine the significance of CYFRA 21-1 in patients with esophageal SCC.. Expression and production of cytokeratin-19 in the authors' six established esophageal SCC cell lines were determined by immunocytochemical staining and enzyme-linked immunoadsorbent assay, respectively. The correlation between serum CYFRA 21-1 levels and expression of cytokeratin-19 in human tumors was investigated by immunohistochemical staining. The correlation between serum CYFRA 21-1 levels and clinicopathologic factors was examined in 48 patients with esophageal SCC, as were SCC antigen and carcinoembryonic antigen (CEA).. Of the 6 cell lines, 5 lines expressed cytokeratin-19 in their cytoplasm and produced soluble cytokeratin-19 fragments. Twenty-three of 48 patients had elevated CYFRA 21-1 levels (>3.5 ng/mL), whereas none of the reference group (consisting of healthy volunteers or patients with benign disease) showed positive levels. The specificity, sensitivity, and accuracy of CYFRA 21-1 were 100%, 47.9%, and 66.7%, respectively. CYFRA 21-1 showed significantly higher sensitivity and accuracy than SCC antigen or CEA (P < 0.05). Univariate analysis revealed that CYFRA 21-1 levels correlated with disease progression (including tumor size, tumor depth, and pTNM stage), resectability, and curability. There was a significant association between the level of CYFRA 21-1 and its intensity of immunohistochemical staining in vitro as well as in vivo.. CYFRA 21-1 appears to be a useful marker for human squamous cell carcinoma of the esophagus.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Serpins; Tumor Cells, Cultured

In Western countries, esophageal squamous cell carcinoma is usually advanced at presentation and is rarely diagnosed in situ. The authors studied an in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length of esophagus, causing dysphagia for solid food in a woman aged 68 years.. The esophagectomy specimen contained a circumferential region of depressed tan mucosa in the middle and lower thirds, bordered above and below by normal squamous mucosa, without ulcer, stricture, or mass. The entire lesion was submitted for histology and evaluated with immunostains for cytokeratins and markers of Paget's cells, p53 mutation, and proliferation.. The lesion involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied the basal layers of the squamous epithelium and were often separated from more superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into nonneoplastic surface and gland duct epithelium was prominent. The tumor cells expressed cytokeratins of low molecular weight, p53 gene product, and proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in Paget's cells in the breast or vulva. No invasion was evident.. This extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid spread of tumor cells. These cells had a phenotype suggestive of origin from primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they lacked the capacity to penetrate the basement membrane. Flat, erythematous areas of esophageal mucosa seen during endoscopy could represent early squamous cell carcinoma and should be biopsied.

Topics: Aged; Basement Membrane; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Division; Deglutition Disorders; Epithelium; Esophageal Neoplasms; Esophagectomy; Female; Gene Expression Regulation, Neoplastic; Genes, p53; Humans; Keratins; Mitosis; Mucous Membrane; Mutation; Paget Disease, Extramammary; Phenotype; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53

Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract.. In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus.. Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found.. BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

Topics: Actins; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Differentiation; Apoptosis; Carcinoma in Situ; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Diagnosis, Differential; Epithelium; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucous Membrane; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; S100 Proteins; Sex Factors; Survival Rate

Processed pseudogenes of residual contaminating genomic DNA interfere with a sensitive detection of cytokeratin 18 (CK18) mRNA by reverse transcription and polymerase chain reaction (RT-PCR). This may cause false-positive results when CK18 mRNA is used as a marker for ectopic tumor cells in specimens from cancer patients. To establish a sensitive CK18 RT-PCR by excluding the amplification of processed pseudogenes, the following strategy was chosen: (a) CK18 pseudogene sequences were cloned from genomic DNA by PCR; (b) cDNA-specific primers were designed on the basis of mismatches between pseudogenes and cDNA; (c) PCR conditions were adjusted to reach maximum sensitivity and specificity. Epithelial cells (1-10) could be detected in 1 mL of blood. Among the numerous CK18 genes homologous to the transcribed gene, at least two different processed pseudogenes exist that are highly homologous to each other and to the exons of the transcribed CK18 gene.

Topics: Biomarkers, Tumor; Bone Marrow; Cardia; DNA; DNA Primers; DNA, Complementary; Esophageal Neoplasms; Humans; Keratins; Lung Neoplasms; Molecular Sequence Data; Polymerase Chain Reaction; Pseudogenes; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Sequence Homology, Nucleic Acid; Stomach Neoplasms

Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes.. In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes.. Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells.. HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Topics: Adult; Brachytherapy; Carcinoma, Squamous Cell; Cell Differentiation; Combined Modality Therapy; Endarteritis; Esophageal Neoplasms; Esophagectomy; Esophagus; Female; Giant Cells; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Necrosis; Neoplasm Proteins; Preoperative Care; Radiation Injuries; Radiotherapy, Adjuvant

To test and optimize photodynamic therapy of early cancers in the upper aero-digestive tract and oesophagus, we sought an appropriate animal model, which was found in the 7,12-dimethylbenz[a]anthracene-induced early squamous cell carcinoma in the Golden Syrian hamster. This chemically induced neoplasm is shown, by histology and immunohistochemistry, to pass through similar stages of early cancer development as its human counterpart. Its time sequence is highly reproducible, leading to a well differentiated carcinoma in situ and microinvasive carcinoma in the hamster cheek pouch over a period of 10 weeks.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Disease Models, Animal; Esophageal Neoplasms; Keratins; Male; Mesocricetus; Mouth Neoplasms; Neoplasm Invasiveness; Photochemotherapy; Precancerous Conditions

Approximately half of the patients diagnosed with localized esophageal cancer die of metastatic disease within the first 2 years following tumor resection. The development of monoclonal antibodies (MAbs) directed against epithelial cell-associated and tumor antigens has enabled the detection of single disseminated tumor cells in secondary organs.. We used MAbs directed against epithelial cell antigens (i.e., cytokeratins) to determine the proportion of patients with esophageal cancer who display isolated tumor cells in their bone marrow. In addition, we evaluated the prognostic significance of a finding of bone marrow tumor cells in patients with esophageal cancer whose tumors were completely resected.. Prior to the initiation of treatment, bone marrow was aspirated from both sides of the upper iliac crests of 90 patients with squamous cell carcinoma of the esophagus. Bone marrow was also obtained from a population of 30 individuals who had not been diagnosed with cancer. Tumor cells in cytologic bone marrow preparations were detected by use of an assay that employed the MAbs CK2 (directed against cytokeratin 18), KL1 (directed against a 56,000-kd pan-cytokeratin component), and A45-B/B3 (directed against an epitope common to cytokeratins 8, 18, and 19) plus the alkaline phosphatase anti-alkaline phosphatasestaining method. Bone marrow biopsies, for conventional histologic examination with Giemsa staining, were performed on 62 patients. The Kaplan-Meier method and the logrank test were used to assess disease-free and overall survival according to the presence or absence of tumor cells in the bone marrow of 42 patients with completely resected tumors. Reported P values are two-sided.. Cytokeratin-positive tumor cells were detected in the bone marrow of 37 (41.1%) of the 90 total patients. The number of tumor cells detected per 10(5) mononuclear bone marrow cells ranged from one to 82. No significant differences in the numbers of disseminated tumor cells were noted for patients diagnosed with tumors at different stages. Only two (3.2%) of 62 bone marrow specimens examined after Giemsa staining showed morphologically identifiable tumor cells. Tumor cells were not detected in the bone marrow of patients who had not been diagnosed with cancer. After a median follow-up of 15.5 months (range, 6-33 months), 15 (79.0%) of 19 patients with completely resected tumors and tumor cells in their bone marrow had relapses compared with three (13.0%) of 23 patients with completely resected tumors and no tumor cells in their bone marrow (P = .019, logrank test). Patients with completely resected tumors and tumor cells in their bone marrow had significantly shorter overall survival than corresponding patients without tumor cells in their bone marrow (P = .036, logrank test).. Dissemination of esophageal cancer cells to the bone marrow is more frequent than expected from the rare occurrence of overt skeletal metastases. In general, the presence of tumor cells in the bone marrow may be an indicator of the disseminatory potential of individual tumors.

Topics: Antibodies, Monoclonal; Azure Stains; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Survival Analysis

We examined full thickness specimens of oesophageal squamous dysplasia from both cancer-free and cancer patients using immunohistochemical labelling for cytokeratin subtypes 10/13 and 14 and for involucrin, binding studies for various lectins, and PAS/D staining before and after diastase treatment. We studied specimens from patients with oesophageal carcinoma (52 normal epithelia, and 49 with mild, 38 with moderate, and 32 with severe dysplasia), and 32 specimens from cancer-free patients (five normal epithelia and 16 with mild and 11 with moderate dysplasia). Abnormal cytokeratin expression patterns in atypical cells, i.e. both cytokeratin 10/13 and cytokeratin 14 immunoreactivity in the same cells was detected in 41 of 99 specimens with dysplasias in cancer patients. Helix aspersa, Erythrina cristagalli and Robinia pseudoacacia binding was consistently negative in atypical cells in squamous dysplasia. The non-atypical layer of squamous dysplasia, which was morphologically indistinguishable from the corresponding layer of normal oesophageal squamous epithelium, showed abnormal involucrin expression in 39/ 101 specimens, Helix aspersa binding in 74/106, diastase sensitive PAS staining in 52/110, Erythrina cristaglli binding in 28/107, and Robinia pseudoacacia binding in 16/100. There were no significant differences in the expression of these markers in dysplasia between cancer patients and cancer-free individuals with the exception of increased Robinia pseudoacacia binding in the non-atypical layer in cancer-free patients. The results indicate that abnormal patterns of cytokeratin expression and lectin binding occur not only in atypical cells but also in non-atypical cells in oesophageal squamous dysplasia.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lectins; Male; Middle Aged; Precancerous Conditions; Protein Binding; Protein Precursors

By using the subtractive hybridization method, two complementary DNA clones differently expressed in rat normal esophageal epithelium and squamous cell carcinoma induced by administration of precursors of N-nitrososarcosine ethyl ester were isolated. A rat homologue of the human 50-kDa type I cytokeratin 14 was cloned for the first time and shown to be expressed preferentially in squamous cell papillomas and carcinomas, whereas it was weakly expressed or absent in normal squamous epithelial cells and in hyperplastic lesions. A rat homologue of the mouse 57-kDa type II cytokeratin showed strong expression in both normal and tumor tissues. These results are well consistent with the reported alteration of keratin subspecies in human esophageal cancers, therefore, encouraging us to use this experimental system as a model for human esophageal carcinogenesis.

Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA, Complementary; Esophageal Diseases; Esophageal Neoplasms; Esophagus; Humans; Hyperplasia; In Situ Hybridization; Keratins; Mice; Neoplasm Proteins; Nitrosamines; Papilloma; Precancerous Conditions; Rats; Rats, Wistar; Recombinant Proteins; Subtraction Technique

To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies.. A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor.. The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors.. We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements.

Topics: Aneuploidy; Antibodies, Monoclonal; Biopsy; Carcinoma, Squamous Cell; Cell Cycle; DNA, Neoplasm; Esophageal Neoplasms; Feasibility Studies; Flow Cytometry; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins

We have developed scanning near-field optical/atomic force microscopy (SNOM/AFM). The SNOM/AFM uses a bent optical fiber simultaneously as a dynamic force AFM cantilever and a SNOM probe. Resonant frequency of the optical fiber cantilever is 15-40 kHz. Optical resolution of the SNOM/AFM images shows less than 50 nm. The SNOM/AFM system contains photon counting system and polychrometer/intensified coupled charge devise (ICCD) system to observe fluorescence image and spectrograph of micro areas, respectively. Cultured cells were stained with fluorescein isothiocyanate (FITC)-labeled anti-keratin antibody or FITC-labeled phalloidin after treatment with Triton X-100. Fluorescence and topographic images were obtained in air and water. The fluorescence images showed clear images of keratin and actin filaments. The SNOM/AFM is perfect to observe biomaterials in liquid with a liquid chamber while the topographic Images showed subcellular structures which correspond to keratin and actin filaments.

Topics: Actins; Air; Carcinoma, Squamous Cell; Chromium; Cytoskeleton; Esophageal Neoplasms; Fluorescein; Humans; Keratins; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Spectrometry, Fluorescence; Tumor Cells, Cultured; Water

To assess cell death and cellular proliferation activity, the apoptosis index, the Ki67 proliferative index and overexpression of p53 protein were evaluated in 69 oesophageal squamous cell carcinomas (ESCC), all surgically resected from Japanese patients. Apoptosis was examined by Gavrieli's method in histological sections, and proved to be significantly related to keratinization and ESCC progression. Overall labelling indices were 15.68 +/- 4.04 (positive/1,000 nuclei) and 6.79 +/- 0.64 respectively, in keratinizing and nonkeratinizing types. The apoptosis labelling index increased, especially in keratinizing lesions, from 4.50 +/- 0.59 with cancer invasion to mucosa through 11.46 +/- 2.70 with involvement of the submucosa up to 21.18 +/- 3.72 in cases of penetration to the muscularis propria or adventitia. The relationship between apoptosis, Ki67 scores and p53 expression was determined in identical cancer nests on serial sections. An inverse correlation was shown between the apoptosis score and the Ki67 score in both keratinizing and nonkeratinizing types. There was no significant correlation between apoptosis score and p53 expression, either overall or separately in keratinizing or nonkeratinizing types of ESCC. Our results suggest that a mechanism of induction of apoptosis similar to that operating in normal epidermis acts in keratinizing ESCC, and that as tumour volume increases, single cell death becomes more frequent.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Division; Esophageal Neoplasms; Humans; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Tumor Suppressor Protein p53

To clarify the keratin staining patterns of invasive carcinoma of the oesophagus, 22 cases of formalin-fixed paraffin-embedded surgical specimens were examined immunohistochemically with the labelled streptavidin biotin method using a panel of six different monoclonal anti-keratin antibodies. The antibody reacted adequately when antigen was retrieved in a microwave oven, and the relationship between morphological characteristics and keratin reaction patterns was analyzed in carcinomas and compared with adjacent histologically normal epithelium. In the normal oesophageal epithelium, AE3 and CK8.12 labelled all layer of cells, KS-1A3, E3 and KL1 labelled suprabasal cells, and LL002 selectively labelled the basal cells. In squamous cell carcinomas, AE3, CK8.12, KL1 and LL002 labelled almost all the tumour cells regardless of their differentiation, E3 only labelled keratinized cells, while marked decrease or loss of KS-1A3 staining was seen in all cases examined. Therefore, the characteristic profile of squamous cell carcinoma was a strong and diffuse expression of keratin 14 and 16, strong but localized expression of keratin 17, and loss of keratin 13 expression. Undifferentiated carcinoma totally lacked all keratin reactivity. The findings suggested that the neoplastic epithelial cells showed different keratin reactivity and distribution compared to normal oesophageal epithelium. In addition, histologically normal epithelium, dysplasia and carcinoma-in-situ adjacent to or overlying carcinoma expressed keratin 14.

Topics: Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Immunoenzyme Techniques; Keratins

Using digoxigenin-labelled cRNA probes, relationships between morphological characteristics and in situ hybridization for cytokeratin (CK)-mRNAs were analysed in cases of squamous-cell carcinoma of variable differentiation and in balloon-cell formation within the oesophageal mucosa. The present results were correlated to our previous findings on normal oesophageal epithelium. Our results from in situ hybridization study on oesophageal squamous-cell carcinoma provide strong evidence that changes in CK expression occur with differences in malignant potential. Cells of poorly differentiated carcinoma lose an ability to produce CK-mRNAs characteristic of their normal progenitor cells. Moderately differentiated and, still more pronounced, well differentiated carcinoma cells retain an ability to produce CKs characteristic of their tissue of origin (CK 6, CK 14, CK 15 and CK 19). Furthermore, well differentiated carcinoma cells may also gain an ability to synthesize new types of CKs that are not characteristic of the normal oesophageal epithelium (CK 8 and CK 18 characteristic of most simple epithelia, and CK 10 characteristic of keratinizing epithelia). Moreover, some oesophageal CK-genes are expressed in an obviously higher amount (CK 6, CK 14, and CK 19), but the expression of genes coding for the oesophageal differentiation-related CKs (CK 4 and CK 13) is obviously decreased or apparently lost. At the interface zone, observed in sections of well differentiated carcinomas, CK 8 and CK 18 mRNA were expressed in intermediate cell layers, and the centrally located cell layers were found positive for CK 10 mRNA. These findings largely extend the existing results from immunoblotting and immunohistochemical studies. The reduced or non-detectable expression of oesophageal differentiation-related CK-mRNAs (CK 4 and CK 13) on the appearance of balloon cells, suggests molecular changes that may be a marker for pathological progression. In addition, the abundant expression of CK 6 and CK 14 mRNA within areas of balloon-cell formation showing basal hyperplasia, and the higher expression of CK 19 in comparison with normal epithelium, points rather to de-differentiation than to normal vertical differentiation of the oesophageal epithelium. Whether CK-mRNAs can be used as biomarkers for evaluation of oesophageal pathologies remains to be further elucidated.

Topics: Carcinoma, Squamous Cell; Epithelium; Esophageal Neoplasms; Esophagus; Gene Expression; Humans; In Situ Hybridization; Keratins; Mucous Membrane; RNA Probes; RNA, Complementary; RNA, Messenger

5 cases of basaloid-squamous carcinoma (BSC) of oesophagus were reported. Their pathological features were: 1. The main component of the tumors were basaloid carcinoma cells. 2. Concomitant squamous cell differentiation. 3. Comedo-like necrosis in the basaloid carcinoma component of the tumor. 4. Hyaline degeneration within the stroma of the basaloid carcinoma nests (PAS+). The immunohistochemistry of keratin 10.11, CEA and EMA in the basaloid carcinoma component of BSC were negative or weak positive, while actin and S-100 were positive in some parts of the tumor sections. This suggested that the carcinoma component was poorly differentiated and somewhat tended to differentiate toward myoepithelia or other directions. We therefore consider that the origin of BSC may be the primitive totipotential cell. BSC occurred more frequently in elderly males. The biological behavior of BSC was highly malignant. Regional lymph nodes or distant organ metastasis were usually found at the first operation. The mean survival period after operation was very short, BSC was therefore considered to be a specific clinicopathological entity.

Topics: Actins; Aged; Carcinoma, Basosquamous; Esophageal Neoplasms; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; S100 Proteins

Immunohistochemical detection of bone marrow micrometastases has been reported as a prognostic marker in colorectal cancer. The aims of this study were to evaluate the potential advantage of flow cytometry as an objective method of identifying and quantifying micrometastatic deposits within bone marrow and to determine the prevalence and quantity of micrometastases in patients undergoing surgery for gastrointestinal cancers.. Flow cytometry was first validated by a controlled "spike" experiment in which varying numbers of neoplastic epithelial cells were added to bone marrow, and cytometry was performed in a blinded fashion. Three neoplastic cell lines (colonic and esophageal) with varying degrees of expression of cytokeratin-18 were used. Epithelial cells were detected by dual staining with fluorescence-labeled, monoclonal anti-cytokeratin, and propidium iodide.. Cytometry reproducibly detected the presence of > or = 10 neoplastic cells per 10(5) marrow cells. Micrometastases were found in 20%-30% of patients undergoing potentially curative resection of colorectal and gastroesophageal adenocarcinomas. There was a trend toward increasing positivity for marrow deposits with advanced Dukes' staging of colorectal cancer.. Flow cytometric assessment of bone marrow is a reliable, objective, and quantitative method of detecting micrometastatic deposits found in a substantial subset of patients undergoing surgery for gastrointestinal adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Marrow Neoplasms; Carcinoma, Squamous Cell; Colorectal Neoplasms; Esophageal Neoplasms; Flow Cytometry; Gastrointestinal Neoplasms; Humans; Keratins; Prognosis; Prospective Studies; Stomach Neoplasms

In this study, I investigated the molecular weights of keratin-subunits in the tissue of esophageal cancer by enzyme-labeled antibody technique with four kinds of antikeratin monoclonal antibodies with different spectrums of reacting keratin-subunits. Further more, the correlation between the molecular weights of keratin-subunits and clinicopathological factors was evaluated, and that between the molecular weights and the prognosis was studied also. The positive rates of four kinds of primary antibodies did not correlate to clinical feature or prognosis, and each primary antibody showed different attitude regarding correlation to histopathological factors. I analyzed the molecular weights of keratin-subunits increased in the carcinoma tissue by the difference of staining intensities of four monoclonal antibodies. The histological findings of the cases with carcinoma tissues in which 48, 56 kd keratins increased were in high malignancy compared with other groups, and their prognosis was significantly poor. Examination of prognostic factors with multivariate analysis revealed that the increase of 48, 56 kd keratins in the carcinoma tissues was the most important determining factor of prognosis next to lymphatic invasion.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Molecular Weight; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Prognosis

The grading of squamous cell carcinoma (SCC) of the esophagus as proposed by the World Health Organization (WHO) has not yet proved to be prognostically significant. Therefore, the prognostic impact of various histologic parameters was investigated and compared with that of the WHO grading.. Hematoxylin and eosin-stained tumor samples from 138 patients with SCC of the esophagus who underwent potentially curative resection (no residual tumor or distant metastases) were evaluated for the following histologic parameters: degree of keratinization, nuclear polymorphism, pattern of invasion, mitotic activity, and inflammatory response. The prognostic impact of these parameters was analyzed by univariate and multivariate survival analyses.. In the univariate analysis, the inflammatory response (P = 0.0006), pattern of invasion (P = 0.0011), and nuclear polymorphism (P = 0.0161) were the only parameters that correlated with survival. However, in a multivariate survival analysis including these parameters, only pattern of invasion (P = 0.0010) and inflammatory response (P = 0.0076) were prognostically significant. Based on these results, a new prognostic score system was defined that correlated significantly with survival in the univariate survival analysis (P = 0.0002). In contrast, the WHO histologic grade was not prognostically significant. In the multivariate Cox regression analysis, the new prognostic score system proved to be an independent prognostic parameter (P = 0.0062), ranking next to pT classification (P = 0.0001) and pN classification (P = 0.0014).. For SCC of the esophagus, histologic grading based on pattern of invasion and inflammatory response had an independent prognostic impact, whereas the grading system proposed by the WHO had no significant prognostic value.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cell Nucleus; Esophageal Neoplasms; Female; Humans; Keratins; Male; Middle Aged; Mitosis; Multivariate Analysis; Prognosis; Survival Analysis

Palmoplantar keratoderma is a group of hereditary disorders of keratinization involving hyperkeratosis of palms and soles. Two different forms of palmoplantar keratoderma have recently been shown to be caused by mutations in the body site-specific keratin 9 gene and in the keratin 1 gene, respectively. Now we have analyzed a large German family with autosomal dominantly inherited palmoplantar keratoderma in association with carcinoma of the esophagus. Linkage to both the type I keratin gene cluster on chromosome 17q distal to the type I keratin genes. Two-point linkage data at D17S801 gave a lod score Zmax - 5.1 at theta = 0.00. Therefore, palmoplantar keratoderma is shown to be heterogeneous clinically as well as genetically and may be caused by mutations in keratins as well as in nonkeratins.

Topics: Chromosome Mapping; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Esophageal Neoplasms; Female; Genes, Dominant; Genetic Linkage; Genetic Markers; Germany; Humans; Keratins; Keratoderma, Palmoplantar; Lod Score; Male; Multigene Family; Pedigree

The distribution of keratins in N-methyl-N'-nitro-N-nitrosoguanidine-induced oesophageal carcinomas in shrews was tested immunohistochemically, using a panel of seven different monoclonal antibodies. The studies were done on methacarn-fixed paraffin-embedded tissue, using the labelled streptavidin biotin method, and the relationship between morphological characteristics and keratin reaction patterns in carcinomas was analysed and compared with that in adjacent "normal" oesophageal epithelium. In the normal oesophageal epithelia, KL1, AE1, AE3, CK8.12, and CK4.62 stained suprabasal cells, 312C8-1 reacted to basal cells, and KS-1A3 labelled all epithelial cells. In squamous cell carcinomas, almost all the cancer cells were labelled strongly by 312C8-1 and weakly by KS-1A3, while a few cells in the centres of the keratinized foci were stained by KL1, AE1, AE3, CK8.12, and CK4.62. Like human oesophageal carcinomas, shrew oesophageal carcinomas maintain expression of human keratin 14, as determined by 312C8-1. The expression of human keratin 13, as determined by KS-1A3, was down-regulated.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Immunohistochemistry; Keratins; Methylnitronitrosoguanidine; Shrews

Topics: Chromosome Mapping; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 17; Esophageal Neoplasms; Female; Humans; Keratins; Keratoderma, Palmoplantar, Diffuse; Male; Pedigree

The immunohistochemical expression patterns of cytokeratins 8 and 18 and vimentin were examined in frozen sections of 120 human mucosal squamous cell carcinomas with special emphasis on the topological distribution in the tumour. This was done in order to evaluate in squamous cell carcinoma a particular expression pattern observed recently by us in transitional cell carcinoma of the urinary tract and designated as an 'interface phenomenon'. This phenomenon implying maximum expression of cytokeratins 8 and 18 at the tumour front, and to a lesser extent also in areas of intratumorous stroma contact, was also found in about 50 per cent of the squamous cell carcinomas examined. It was even found for vimentin, which contrasted with transitional cell carcinoma. The percentages of occurrence of the phenomenon varied for the different sites of origin of the tumour. Tumour grade did not influence the results. These findings further support the idea that invasive carcinoma cells interacting with the stromal micro-environment display a characteristic intermediate filament phenotype that deviates from the pattern expected on the basis of their direction of differentiation. These changes might reflect phenotype involved in invasive, migrating, and proliferating activities.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Proteins; Vimentin; Vulvar Neoplasms

In order to clarify the histogenesis and the direction of differentiation of spindle-cell and sarcomatous components of esophageal carcinosarcoma, 20 cases of the disease were reviewed histologically and immunohistochemically using the avidin-biotin-peroxidase complex method with monoclonal and polyclonal antibodies to various keratins, vimentin, desmin, muscle specific actin and S-100 protein. A gradual transition between carcinomatous and spindle cell sarcomatous components was present histologically in all 20 cases. Positive immunoreactivity for keratins was found in carcinomatous areas in all cases. Spindle cells in the transitional areas were positive for keratins in nine cases and for vimentin in five. Two cases demonstrated trace positive reactions to both keratin and vimentin in the same areas of transitional spindle cells between carcinomatous and sarcomatous components. The sarcomatous component showed an immunohistochemically positive reaction for vimentin in ten cases and for desmin in two. In one of the 20 cases, chondrosarcomatous cells were seen which showed a positive reaction to S-100 protein but were negative to keratin. The findings strongly suggested that neoplastic epithelial cells may show dedifferentiation to transforming spindle cells and also disdifferentiation to non-epithelial sarcoma like chondrosarcoma and leiomyosarcoma.

Topics: Actins; Adult; Aged; Anaplasia; Carcinoma, Squamous Cell; Carcinosarcoma; Cell Nucleus; Cytoplasm; Desmin; Esophageal Neoplasms; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; S100 Proteins; Sarcoma; Vimentin

Topics: Adenocarcinoma; Aged; Esophageal Neoplasms; Etretinate; Hair Diseases; Humans; Keratins; Male; Paraneoplastic Syndromes

In a group of 245 cases of primary carcinoma of the esophagus the authors found three cases of adenoid cystic carcinoma (ACC). Clinical and pathologic data of those patients (one female and two male; age range, 49-74 years) were analyzed. Tumors were localized in the middle third of the esophagus. One patient lived 15 months after surgery. Another is a case of early ACC who has been living 4.5 years after surgery and is without specific symptoms. The third patient had not had surgery and died 13 months after the onset of dysphagia. An autopsy showed only a locally invasive tumor growing into the surroundings of the esophagus, and regional lymph node metastases without distant parenchymal metastases. These findings support pathologic and biologic similarities between ACC of the esophagus and ACC of the salivary glands. There are synchronous tumors of the esophagus and the vital localization which makes the prognosis of ACC of the esophagus worse than ACC of the salivary glands.

Topics: Aged; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Collagen; Esophageal Neoplasms; Female; Humans; Hyalin; Immunohistochemistry; Keratins; Laminin; Lymphatic Metastasis; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; S100 Proteins

A case is presented of a rhabdomyosarcoma of the oesophagus with a description of the cytology, light microscopy, and immunocytochemical findings and a discussion of spindle cell tumours occurring at this site. Cytologically, large bizarre shaped pleomorphic cells were seen in which desmin was demonstrated in order to confirm the diagnosis after destaining a Papanicolaou stained slide and restaining it with antibody to desmin.

Topics: Carcinoma; Carcinosarcoma; Desmin; Diagnosis, Differential; Esophageal Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Rhabdomyosarcoma; Sarcoma; Staining and Labeling; Vimentin

Basaloid-squamous carcinoma of the larynx, pharynx and base of tongue and the so-called adenoid cystic carcinoma of the oesophagus are rare but distinctive tumours associated with a grave prognosis. They occur most commonly in elderly males and present at an advanced stage. Our study of four such laryngeal tumours and five such oesophageal tumours shows that they are histologically and immunohistochemically identical, providing support for the idea that they are the same tumour type. They show a biphasic pattern in which basaloid tumour is intimately associated with a neoplastic squamous component which can be invasive or in situ. The basaloid component is in the form of invasive lobules with frequent comedo-necrosis and hyalinization. The constituent cells possess pale pleomorphic nuclei with frequent mitoses. Immunoreactivity for cytokeratin in the basaloid component is remarkable for its absence or weak and focal nature. Review of the literature shows that only a few cases of 'adenoid cystic carcinoma' of the oesophagus are bona fide examples of adenoid cystic carcinoma as it occurs in the salivary glands, while the others are identical to basaloid-squamous carcinoma of the upper aerodigestive tract. Their distinction is important because genuine adenoid cystic carcinoma is much less aggressive than basaloid-squamous carcinoma.

Topics: Actins; Aged; Antibodies; Carcinoembryonic Antigen; Carcinoma, Adenoid Cystic; Carcinoma, Basosquamous; Diagnosis, Differential; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Pharyngeal Neoplasms; Prognosis; S100 Proteins; Vimentin

Primary small cell carcinoma of the oesophagus (SCCO), histologically indistinguishable from its counterpart of the lung, is a rare tumour. Less than 100 cases are reported. A review of 558 consecutive patients with oesophageal carcinomas referred to our department revealed seven cases. These were studied and compared to a survey of 80 cases collected from 24 reports. The present results, as well as the survey, indicate a poor prognosis with rapid and widespread dissemination, and that death is attributed to distant metastases rather than local failure. Freedom from local symptoms was achieved in all seven patients, regardless of therapy modalities employed. A complete response of the primary lesion was observed in three patients after chemo- and subsequent radiotherapy. According to these findings the most suitable treatment approach seems to be the same as for small cell carcinoma of the lung. A detailed immunohistochemical analysis revealed more characteristics similar to small cell carcinoma of the lung than that of the skin, viz 'Merkel cell carcinoma'.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Small Cell; Combined Modality Therapy; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mucin-1; Neoplasm Metastasis; Prognosis; Remission Induction; Retrospective Studies

A case report of a choroidal metastasis from an oesophageal squamous cell carcinoma is described. The computerised tomographic, ultrasonographic, histologic and immunohistochemic findings are presented with a review of the literature.

Topics: Carcinoma, Squamous Cell; Choroid Neoplasms; Esophageal Neoplasms; Fluorescein Angiography; Fundus Oculi; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Tomography, X-Ray Computed; Ultrasonography

Subdermal metastatic nodules in a 62-year old male patient with esophageal carcinoma contained both carcinomatous and chondroid areas. The carcinomatous areas showed the histology of poorly differentiated squamous cell carcinoma, and light microscopically an apparent transition could be traced from carcinomatous cells to chondroid cells. In the chondroid cells, the characteristics of chondrocytes were demonstrated by light microscopic, electron microscopic, histochemical and immunohistochemical studies, although nuclear atypism was evident, suggesting their malignancy. Furthermore, immunohistochemical studies showed that some chondroid cells contained both keratin proteins and squamous cell carcinoma antigen, which were also found in the carcinomatous cells. These findings together with the light microscopic observations suggest that chondroid cells are derived from squamous cell carcinoma cells.

Topics: Carcinoma, Squamous Cell; Cartilage; Collagen; Esophageal Neoplasms; Extracellular Matrix; Humans; Immunoenzyme Techniques; Keratins; Male; Metaplasia; Microscopy, Electron; Middle Aged

Anticytokeratin antibody AE1 was studied immunohistochemically in 56 surgical specimens of esophageal carcinoma. Relationships between morphologic characteristics and AE1 reaction patterns were analyzed in carcinomas and adjacent epithelium. Infiltrating carcinomas had three types of AE1 patterns that paralleled degrees of differentiation. Type 1 pattern was present in well-differentiated carcinomas characterized by cytoplasmic staining of polyhedral cells. Types 2 and 3 were seen in poorly differentiated and undifferentiated carcinomas in different percentages, characterized by all cancer cells stained, with cellular membrane and cytoplasm stained or all unstained, respectively. In normal esophageal epithelium, basal cells were the major population that was AE1 positive. In hyperplasia basal cells showed two kinds of changes, either reduced/lost AE1 staining accompanied by AE1 expression in spinous cells or retained/increased AE1 reactivity. In dysplasia and carcinoma in situ, abnormal cells had reaction patterns in which they lost or increased AE1 expression. Findings indicate that different degrees of differentiation of infiltrating esophageal carcinoma cells have differing expressions of cytokeratins and that monoclonal antibody AE1 can serve as a biomarker identifying early abnormalities in esophageal epithelial cells having increased predisposition to malignancy. Molecular mechanisms of AE1 cytokeratin expression in esophageal epithelium are also discussed.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Differentiation; Epithelium; Esophageal Neoplasms; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Staining and Labeling

The expression of phenotypes of cultured cancer cells might be associated with cancer cell differentiation. By using the electron microscope and monoclonal antibodies against cytokeratins, PKK1, PKK2 and PKK3, the expression of cytokeratins and tonofilaments of normal embryonic esophageal epithelial cells and esophageal cancer cells were studied. Both PKK1 and PKK2 cytokeratins were detected in embryonic esophageal and esophageal cancer cells, but PKK3 was not present. This indicated that these were squamous but not glandular epithelial cells. Also, a much greater degree of expression of PKK1 and PKK2, tonofilaments and desmosomes was observed in differentiated embryonic squamous esophageal epithelial cells and in DMSO or retinamide induced differentiated esophageal cancer cells than in undifferentiated esophageal cancer cells.

Topics: Animals; Cell Differentiation; Cytoskeleton; Esophageal Neoplasms; Humans; Intermediate Filaments; Keratins; Phenotype; Tumor Cells, Cultured

Two types of high grade dysplasia were associated with invasive carcinomas. The first, deeply localized, had a pagetoid appearance and a particular phenotype: the dysplastic cells had keratins of low molecular weight rarely present in the esophagus; keratins of stratified epithelia were absent. This dysplasia was probably the origin of undifferentiated invasive carcinoma with which it was often associated. The second type, transepithelial, extended through the entire thickness of the epithelium. The abnormal cells presented some differentiation and stained positive for keratins of stratified epithelia. This dysplasia was often associated with differentiated squamous cell carcinoma. An intermediate-type dysplasia shared some characteristics with both main types. Several types of dysplasia and several areas of differently differentiated carcinoma were often associated in the same case. The evolutional potential of the different dysplasias is not known.

Topics: Carcinoma; Epithelial Cells; Epithelium; Esophageal Neoplasms; Esophagus; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Phenotype

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Staging

Two cases of an esophageal carcinoma with an adenoid cystic differentiation are presented. The first was diagnosed histologically as typical adenoid cystic carcinoma, and the other as being a basal cell carcinoma with an adenoid cystic differentiation. We further investigated these tumors and normal esophageal specimens to determine their histological origin by immunohistochemical staining with either polyclonal or monoclonal antibodies to different classes of human keratin. It was found that both tumors were similar in their reactivities with the anti-keratin antibodies to basal cells of the surface squamous epithelia, but not to the cells composing the esophageal glands, suggesting that they were of basal cell origin.

Topics: Aged; Antibodies, Monoclonal; Carcinoma, Adenoid Cystic; Carcinoma, Basal Cell; Esophageal Neoplasms; Humans; Keratins; Male; Staining and Labeling

Sera drawn from healthy individuals, patients with squamous cell carcinoma (SCC) of the oesophagus and patients with mild active oesophagitis were examined for autoantibodies to cytoskeletal proteins extracted from the normal oesophageal keratinocyte or from 2 carcinoma cell lines, each of the latter have a simple cytoskeleton. Using a radioimmunoassay with normal oesophageal cytokeratins as bound antigen, 86 normal, 76 SCC and 14 oesophagitis sera were compared. No significant difference in autoantibody titre was found. When the bound antigen was changed to one containing predominantly simple epithelial cytokeratins a significant increase (32% P less than 0.001) was noted in the SCC category only. Western blots using simple epithelial cell extracts as antigen revealed autoantibodies to cytokeratins 8, 18 and 19 as well as to one other unidentified protein in most SCC sera, and in some normal sera. Antibodies to cytokeratin 18 predominated. Normal and SCC sera were applied using indirect immunofluorescent techniques to normal oesophageal keratinocytes, SNO oesophageal SCC cells and HeLa cells grown in vitro. Autoantibodies to oesophageal cytokeratins were, with few exceptions, barely detectable. Strong reactions were noted against SNO and HeLa cytoskeletal components, but also against nuclear membrane and nucleolar determinants. These experiments suggest that raised levels of autoantibodies to certain cytoskeletal and nuclear determinants may be a feature of oesophageal cancer.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Blotting, Western; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagitis; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged

Two patients developed extremely bizarre (pseudomalignant) granulation-tissue reactions in the larynx and facial sinuses, following radiation therapy for carcinoma. Containing pleomorphic spindle cells and numerous (sometimes atypical) mitotic figures, both tumefactive lesions simulated high grade malignancies. While the pleomorphic cells contained vimentin immunoreactivity, they were nonreactive for low or high molecular weight keratin. Flowcytometric study of paraffin-embedded tissues revealed DNA indexes of 0.75 and 1.0. Neither recurred locally nor spread distantly after therapy. Their granulation-tissue growth pattern, and the presence of stromal and endothelial cells showing similar degrees of cytologic atypia were central to their recognition as benign. These findings show that severely atypical, sometimes aneuploid, granulation-tissue reactions can occur following radiation exposure. Care should be taken not to misinterpret these lesions as malignant.

Topics: Aged; Diagnosis, Differential; Esophageal Neoplasms; Factor VIII; Flow Cytometry; Granulation Tissue; Histocytochemistry; Humans; Hypopharynx; Immunoenzyme Techniques; Infant; Keratins; Male; Maxillary Sinus Neoplasms; Neoplasm Recurrence, Local; Polyps; Radiotherapy; Vimentin

Fifty five formalin-fixed, paraffin-embedded, pronase-pretreated esophageal carcinomas and their metastatic nodes were studied immunohistochemically with peroxidase-antiperoxidase technique for keratins using polyclonal antibody (DAKO), antibody against keratins of keratinocyte (KL1), against high molecular weight-keratin (EY904), and against low molecular weight-keratins (EY902, PKK1). The suprabasal layer of the esophageal epithelium was stained diffusely with DAKO, KL1 and EY902 and faintly or locally with EY904 and PKK1. Esophageal ducts were positive with any antibodies. We classified staining pattern of the esophageal carcinoma according to the localization and proportion of the positive cells in the cancer nests. No significant correlation of the staining pattern was found between the primary lesions and metastatic nodes. The proportion of the EY904-positive cells correlated significantly with the degree of lymph node metastasis, histologic stage, and prognosis by rank correlation method and generalized Wilcoxon test, but not with the depth of invasion nor histologic degree of differentiation. The proportion of DAKO-positive cells correlated significantly only with histologic degree of differentiation. It was supposed that esophageal carcinomas with high molecular weight-keratin had less tendency to metastasize to nodes.

Topics: Antibodies; Esophageal Neoplasms; Histocytochemistry; Humans; Keratins; Lymphatic Metastasis; Molecular Weight; Staining and Labeling

Five cases of an uncommon esophageal tumor consisting of a mucosal squamous cell carcinoma that surrounds a polypoid mass of spindle cells were examined. The spindle cell component was composed of elongated cells with blunt nuclei, admixed with multinucleated giant cells. Reticulin fibers enveloped individual cells, and abundant collagen was present. Thirteen to 69 mitotic figures occurred per 10 high-power fields. Electron microscopy showed dilated cisternae of rough endoplasmic reticulum and peripheral intermediate filaments within the cytoplasm. Intermediate-type junctions (zonulae adherens) and subplasmalemmal linear densities connected some cells. No tonofibrillar bundles or desmosomes (maculae adherens) were present. Immunoperoxidase stains detected no keratin in the spindle cells. Alpha-1-antichymotrypsin and alpha-1-antitrypsin were in the spindle cells in five of five and three of five cases, respectively. The absence of desmosomes, tonofibrillar bundles, and keratin and the presence of alpha-1-antitrypsin and alpha-1-antichymotrypsin favor fibrohistiocytic differentiation of the spindle cell component.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged

Eight cases of esophageal carcinoma with prominent spindle cells (carcinosarcoma or pseudosarcoma) were studied using the avidin-biotin immunoperoxidase method and monoclonal antibodies to various keratins and vimentin. In all eight cases positive immunoreactivity for keratin was found in carcinomatous areas and for vimentin, in the spindle cells. It is interesting that five cases demonstrated focal immunoreactivity to keratin in the spindle cell component. Trace positivity to vimentin was seen in the carcinomatous areas in one case. These findings are consistent with the hypothesis that esophageal carcinoma with prominent spindle cells is of epithelial origin and may represent a morphologic variant of squamous cell carcinoma.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma; Carcinoma, Squamous Cell; Carcinosarcoma; Esophageal Neoplasms; Female; Fibroma; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Molecular Weight; Vimentin

Human esophageal carcinoma cell lines (8 cell lines) differed from their normal counterpart in terms of their morphological appearance, growth properties, and the expression of certain differentiated functions, namely keratin proteins and cross-linked envelopes. In contrast to normal human esophageal keratinocytes, the carcinoma cells were pleomorphic and tended to pile up in an unorganized fashion. When grown under optimal growth conditions the carcinoma cells generally grew to a higher saturation density than their nontransformed counterpart; their generation times were variable. Transformed cells grew better under stringent growth conditions (e.g., decreased serum and no additional growth factors except hydrocortisone) than did nontransformed human esophageal keratinocytes but their growth was still restricted under these conditions. The carcinoma cells retained a requirement for a 3T3 feeder layer when grown at clonal densities (5 X 10(3) cells/60-mm dish) but could be passaged and maintained without a feeder layer if plated at higher than clonal densities (10(5) cells/60-mm dish). All cell lines grew in an anchorage-independent fashion in soft agarose although the colony forming efficiency and size of the colonies varied among the different cell lines. Not all anchorage-independent cell lines were tumorigenic. Tumorigenic potential was greatly augmented by the use of cell lines derived from soft agarose selected clones. Altered expression of keratin proteins and cross-linked envelopes was observed in the carcinoma cell lines and generally reflected those changes seen in primary esophageal carcinomas. In two cell lines (HCE-4 and HCE-6), the synthesis of the Mr 44,000 (analogous to Rheinwald's Mr 40,000 keratin) and 52,000 keratins was suppressed coincident with the appearance of the 67 Kd keratin in tumors derived from these cell lines. These keratin patterns were once again reversed in cell lines recultured from these tumors, suggesting that the expression of these specific keratins is subject to extrinsic growth regulation. Another feature of terminal differentiation in keratinocytes, cross-linked envelope formation, was found to be significantly altered (reduced) in most but not all human esophageal carcinoma cell lines.

Topics: Animals; Carcinoma; Cell Differentiation; Cell Division; Cell Line; Cell Membrane; Cells, Cultured; Epithelium; Esophageal Neoplasms; Esophagus; Humans; Keratins; Lasalocid; Mice; Mice, Nude; Molecular Weight; Neoplasms, Experimental

Squamous cell carcinomas have recently been shown to contain increased numbers of epidermal growth factor (EGF) receptors. Since EGF has an important role in epithelial growth and differentiation, it is possible that modulation of its receptor may have an important role in neoplasia. In an attempt to further explore the relationship of EGF receptor expression to malignant transformation, we examined 14 squamous cell carcinoma cell lines of the esophagus for the number and affinity of EGF receptors. Seven cell lines were newly isolated by this laboratory and recently characterized. The seven additional cell lines were obtained from Japan (4 cell lines) and South Africa (3 cell lines). Surprisingly, we found that esophageal carcinomas contained lowered quantities of surface EGF receptors (2- to 100-fold) and that the affinity of the EGF receptor was increased (6- to 100-fold) when compared to normal esophageal epithelial cells. Moreover, the biologic response of esophageal carcinoma cells to EGF differed markedly from that of other squamous cell tumor cells exhibiting elevated numbers of receptors, such as A431 and SCC-15. Human esophageal carcinoma cells were maximally stimulated by the addition of 5 ng/ml of EGF, similar to normal esophageal keratinocytes, but in contrast to normal cells were not inhibited by the higher concentrations tested (up to 40 ng/ml). On the other hand, addition of any EGF to the medium (beyond that normally present in serum) was found to dramatically inhibit the growth of A431 and SCC-15 cells. Our findings indicate that squamous cell neoplasia is not dependent upon increased numbers of cell surface EGF receptors, that EGF receptor number may have a determinant role in EGF cell toxicity, and that the stimulatory response of cells to EGF may reflect a complex function of EGF receptor number, affinity, and occupancy.

Topics: Carcinoma, Squamous Cell; Cell Line; Epidermal Cells; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Esophagus; Female; Humans; Japan; Keratins; Kinetics; Receptors, Cell Surface; South Africa; Vulvar Neoplasms

Immunohistochemical and electron microscopic examinations were made of a carcinosarcoma of the esophagus in an 80-year-old man. An immunohistochemical examination showed that sarcomatous spindle cells were vimentin-positive, whereas squamous carcinoma cells were keratin-positive. No coexistence of vimentin and keratin in a single tumor cell was found. Electron microscopically, the sarcomatous spindle cells were characterized by well-developed rough endoplasmic reticulum, abundant intermediate filaments, and the occasional presence of peripheral aggregates of microfilaments. No definite desmosomes were identified among these cells. These results appear to indicate that most of the spindle-shaped tumor cells assume fibroblastic cellular features and synthesize the intermediate filament protein usually expressed in mesenchymal cells, even though such tumor cells could be epithelial in origin.

Topics: Aged; Antibodies, Monoclonal; Antigen-Antibody Complex; Carcinosarcoma; Esophageal Neoplasms; Humans; Keratins; Male; Microscopy, Electron; Vimentin

Papillomas (40) and squamous cell carcinomas (75) were examined for the presence of three keratin proteins with the use of an immunohistochemical technique. Polyclonal keratin antibody (TK, detecting 41 to 65 kDa keratin) and monoclonal antibodies KL1 and PKK1 (55 to 57 kDa and 41 to 56 kDa, respectively) were used. Squamous epithelium in normal oral mucosa showed marked TK staining in cells of upper strata and relatively slight staining in basal layer cells, moderate KL1 staining in spinous and granular layers and was negative in basal cells. Positive PKK1 staining was noted in cells of the basal layer. Columnar epithelium in the nasal mucosa showed TK staining in all layers, KL1 staining on the apical side of epithelial cells and trace or negative staining in basal layer cells. There was moderate PKK1 staining along the apical side of cells and variable staining in basal cells. Keratin distribution in oral papillomas was similar to that in normal oral epithelium, whereas in nasal and nasopharyngeal papillomas, keratin distribution was restricted to the upper layers. Tonsillar papillomas showed a strong TK reaction, negative KL1 in upper layer cells, and marked PKK1 staining in basal cells. Well-keratinized squamous carcinomas indicated an irregular TK distribution and decreased KL1 and negative PKK1 stainings. Intermediate and poorly differentiated keratinizing squamous carcinoma showed irregular staining patterns for the three classes of keratins studied. Immunohistochemically detectable keratins utilizing monoclonal antibodies were described as useful markers of epithelial tumors of squamous origin. Keratin expression within benign tumors was related to normal regional distribution, whereas in malignant tumors, keratin distribution was irregular in its distribution profile.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Nasal Mucosa; Nasopharyngeal Neoplasms; Papilloma

The unlabeled antibody peroxidase-antiperoxidase technique was used to examine esophageal neoplasms for the tumor markers beta-human chorionic gonadotropin, human placental lactogen (HPL), alpha-fetoprotein, carcinoembryonic antigen (CEA), and nonspecific cross-reacting antigen (NCA) before and after xenotransplantation to athymic nude mice. In addition, keratin was used as an epithelial cell marker. Immunoreactive beta-human chorionic gonadotropin was detected in four of seven primary tumors and in three of seven xenografts. Two of seven primary tumors contained HPL immunoreactive cells while four of seven tumor xenografts had HPL immunoreactivity. alpha-Fetoprotein was detected in two of seven primary tumors and in one of seven xenografts. NCA and CEA were detected in six of seven primary tumors and in all tumor xenografts. Five of seven primary neoplasms and six of seven tumor xenografts were found to contain both NCA and CEA, while one tumor and its xenografts displayed only NCA immunoreactivity. All seven primary carcinomas displayed keratin immunoreactivity, but only six of the seven xenograft tumors showed keratin positive cells. When a tumor marker was detected in a primary tumor, it was usually found in at least some of the xenografts arising from that tumor. However, marker loss did occur with repeated passage of tumors in some cases. On the other hand, markers were expressed in xenografts which were not present in the corresponding primary tumor. In three instances, HPL was detected in xenografts derived from HPL negative primary carcinomas. This was also true for CEA and NCA in one case. These results show that tumor markers are expressed to varying degrees by tumors growing as xenografts in nude mice. In primary tumors, HPL is associated with poorly differentiated squamous cell carcinomas and this marker was found to appear in HPL negative tumors as the tumor cells became less differentiated while growing as xenografts in nude mice.

Topics: alpha-Fetoproteins; Animals; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma; Cell Adhesion Molecules; Chorionic Gonadotropin; Esophageal Neoplasms; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Mice; Mice, Nude; Neoplasm Transplantation; Placental Lactogen

The 8-nm keratin filament is a major component of the cytoskeleton of epithelial cells and epithelial-derived cancers (carcinomas). Recently, it has been shown that the pattern of keratins produced by an esophageal epithelial cell undergoes change upon malignant transformation. In order to evaluate the potential importance of these differences in providing improved diagnostic techniques for pathology, we have investigated the consistency of the patterns of keratins expressed in normal esophageal epithelium, squamous cell carcinoma (SQCC) of the esophagus, and cultured esophageal epithelial cells. In six patients, the keratin pattern expressed by SQCC of the esophagus and corresponding normal esophageal epithelium was consistently different as judged by immunoblot analysis of electrophoretically separated protein extracts. Whereas the SQCCs typically expressed major keratins with molecular weights of 58,000, 56,000, 50,000, and 46,000, the normal esophageal epithelium produced two major keratins with molecular weights of 58,000 and 52,000 and a minor keratin with a molecular weight of 56,000. When normal esophageal epithelial cells were grown in tissue culture, their keratin pattern changed, and keratins with molecular weights of 58,000, 56,000, 52,000, 50,000, 46,000, and 40,000 were expressed. Although some minor variations in keratin patterns were seen, the major differences in keratin pattern expressed by normal esophageal epithelial tissue, SQCC of the esophagus, and cultured esophageal cells were consistent and reproducible.

Topics: Antibody Specificity; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Epithelium; Esophageal Neoplasms; Esophagus; Fluorescent Antibody Technique; Humans; Keratins; Molecular Weight

When compared to normal esophageal epithelium, marked alterations in keratin protein and cross-linked envelope expression were found in human esophageal carcinomas. Examination of the pattern of keratin proteins extracted from either several primary esophageal tumors or carcinomas xenotransplanted in nude mice revealed a dramatic reduction in the amount of keratin protein, especially in the Mr 52,000 to 61,000 range. In seven of eight of the primary tumors, the major Mr 52,000 and Mr 61,000 esophageal keratins were not detected, and the remaining tumor exhibited a marked reduction in these two keratins. The major Mr 57,000 and minor Mr 59,000 esophageal keratins were found in varying but reduced amounts in the different tumors. The major Mr 57,000 keratin seemed to be the most conserved keratin of this intermediate-molecular-weight keratin class (Mr 52,000 to 61,000). In contrast, the lower-molecular-weight keratins (Mr 46,000 to 50,500) were usually conserved in the carcinoma cells and were present at levels approximating that of the nontransformed counterpart. The minor Mr 37,000 and 44,000 keratins from normal esophageal epithelium were retained in the tumor cells but often in reduced amounts. The expression of another differentiated function, cross-linked envelopes, in the carcinoma cells varied from unimpaired to severely restricted capacity to form envelopes. In conclusion, specific alterations in keratin protein and cross-linked envelope expression were found in human esophageal carcinomas.

Topics: Animals; Epithelium; Esophageal Neoplasms; Esophagus; Humans; Keratins; Mice; Mice, Nude; Molecular Weight; Mutation; Neoplasm Transplantation; Skin; Transplantation, Heterologous

A case of polypoid carcinosarcoma of the esophagus is presented. Histologically the bulk of the tumor consisted of a sarcomatous tissue having large foci of osseous and cartilagenous differentiation and infiltrating deeply the wall, whereas a superficially, invasive squamous cell carcinoma associated with in-situ carcinoma was located at the base and luminal surface of the polypoid tumor. Intermingling of the carcinomatous and sarcomatous elements was found only in areas where they appeared to be collided. Ultrastructurally the sarcomatous portion contained cells with fibroblastic features but with no typical epithelial characteristics. Immunoperoxidase staining of the paraffin-embedded histologic sections for keratin proteins revealed, however, some positive spindle cells indicative of epithelial nature in the sarcomatous area, but the great majority of the sarcoma cells were devoid of keratin. These combined findings strongly suggest that the sarcomatous component in our case of true carcinosarcoma is derived from mesenchymal transformation (metaplasia) of the squamous carcinoma cells. The findings were discussed in light of the previous pertinent literature.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Carcinosarcoma; Esophageal Neoplasms; Humans; Keratins; Male; Middle Aged; Neoplasms, Multiple Primary; Osteoclasts

Twenty-five primary gastrointestinal carcinomas have been studied using immunofluorescence microscopy with affinity-purified antibodies to prekeratin and to vimentin. The tissues were alcohol fixed and paraffin embedded before use. In all cases (i.e., one case of esophagal carcinoma, seven stomach carcinomas, and 17 large bowel carcinomas) the tumor cells are stained by antibodies to prekeratin. In cases in which only very few tumor cells are present, such as signet ring carcinoma, immunofluorescence with prekeratin antibody provides an easy way to visualize single tumor cells. When the same specimens were tested with antibodies to vimentin, the tumor cells were unstained, and only the fibroblasts and vessels of the stroma were decorated. Four of the tumors were also negative when tested with antibodies specific for either desmin, or glial fibrillary acidic protein or neurofilaments. Three metastases to the abdominal region from tumors originating in the ovary, stomach, and large bowel were like the primary tumors in that the tumor cells were positive when stained with antibodies to prekeratin and negative when tested with the antibodies to vimentin.

Topics: Adenocarcinoma; Antibodies; Carcinoma, Squamous Cell; Colonic Neoplasms; Cytoskeleton; Esophageal Neoplasms; Fluorescent Antibody Technique; Gastrointestinal Neoplasms; Humans; Keratins; Muscle Proteins; Neoplasm Metastasis; Protein Precursors; Stomach Neoplasms; Vimentin

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Granuloma; Humans; Keratins; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Radium; Skin Diseases; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms