bromochloroacetic-acid and Stomach-Neoplasms

Plexiform angiomyxoid myofibroblastic tumor (PAMT), also known as plexiform fibromyxoma, is a rare distinctive benign intramural tumor, typical of gastric antrum, commonly causing mucosal ulceration with upper gastrointestinal bleeding and anemia, effectively treated by complete surgical resection usually accomplished by distal gastrectomy.. We herein report a 47-year-old man presenting with a syncopal episode, regurgitation and epigastric discomfort, bearing a gastric antral myxoid plexiform tumor positive for α-smooth muscle actin, vimentin and, partially, for caldesmon, desmin, and CD10; CD117, DOG1, CD34, S100, CAM5.2, CK20, CK7, EMA, p53, CDX2, chromogranin A, synaptophysin, anaplastic lymphoma kinase, Melan-A, and HMB-45 were all negative. All these features are typical of PAMT. Of note, focal positivity for AE1/AE3 and pan-CK KL1 was also present.. The finding of a focal keratin expression in PAMT contributes to enlarge the immunophenotypic spectrum of this tumor type and is relevant for avoiding presurgical misdiagnoses which could ultimately lead to inappropriate overtreatment of patients with PAMT.

Topics: Biomarkers, Tumor; Fibroma; Gastrectomy; Humans; Keratins; Male; Middle Aged; Stomach Neoplasms

Topics: Aged; Carcinoma, Medullary; Carcinoma, Squamous Cell; Diagnosis, Differential; Gastrectomy; Humans; Keratins; Lymphoma; Melanoma; Middle Aged; Neoplasm Staging; Retrospective Studies; RNA, Viral; Stomach Neoplasms

Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features. Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a high-grade adenocarcinoma, identical with that of the breast. Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

Topics: Adenocarcinoma; Adult; Ascites; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Female; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms

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

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

Gastric adenocarcinoma is one of the most common gastrointestinal (GI) malignancies, especially among Japanese adults, but represents only 0.05% of all malignant pediatric GI tumors. We report a case of gastric adenocarcinoma arising at the esophageal gastric junction of an 11-year-old girl. The tumor was polypoid, measuring 3.0 x 3.0 x 1.2 cm and was light gray and partially red in color with a stalk. Light microscopic examination of the lesion demonstrated adenocarcinoma of variable degrees of both architectural and nuclear atypia with invasion into the submucosa. Immunohistochemical findings of cytokeratin subtypes revealed positive immunoreactivity for cytokeratin subtypes 8, 19 and 20 and negative for 5/6/18, 7, 13 and 14, which is consistent with those of gastric adenocarcinoma. The patient was alive and well 12 months postoperatively.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Child; Cisplatin; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Humans; Immunohistochemistry; Keratins; Stomach Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Differentiation; Colorectal Neoplasms; Female; Humans; Keratins; Neoplasms, Glandular and Epithelial; Oropharyngeal Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Urologic Neoplasms

Topics: Adenocarcinoma; Biomarkers, Tumor; Bone Marrow; Germany; Humans; Japan; Keratins; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate; United States

We report a case of primary gastric choriocarcinoma with liver metastasis. The mixed histologic patterns included adenocarcinoma, undifferentiated carcinoma, and choriocarcinoma. Immunohistologic staining for the beta-subunit of human chorionic gonadotrophin (beta-HCG) showed positive results in the choriocarcinoma, adenocarcinoma, and normal mucosal gland. However, positive HCG cells were present at different intensities in the choriocarcinoma, adenocarcinoma, and normal mucosal gland. The level of HCG was significantly increased in serum. This unusual tumor probably resulted from dedifferentiation of a primary adenocarcinoma or developed directly from the mucosal glands.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mucin-1; Neoplasms, Multiple Primary; Stomach Neoplasms

Cutaneous metastasis from gastric carcinoma is uncommon. We describe a patient with a metastasis from gastric carcinoma to a congenital melanocytic nevus. The diagnosis was confirmed by positive immunohistochemical staining for cytokeratin 20 and lack of cytokeratin 7.

Topics: Carcinoma; Collagen; Cytoplasm; Female; Hair; Humans; Keratins; Melanocytes; Middle Aged; Neoplasms, Multiple Primary; Nevus, Pigmented; S100 Proteins; Skin Neoplasms; Stomach Neoplasms; Sweat Glands; Vimentin

Evidence of dynamic development of cytokeratin (CK) 18-positive disseminated tumor cells in bone marrow of curatively resected cancer patients has implicated a subclinical minimal residual disease as a biologically relevant component in solid cancer. However, differentiation between irrelevant shed cells and those cells potentially capable of causing later recurrence has not yet been made. In parallel, accumulating data show functional association of the urokinase plasminogen activator (uPA) system and the membranous uPA receptor (uPA-R) with the capacity of a tumor cell for invasion and metastasis. The present study was designed to find descriptive evidence in vivo concerning whether uPA-R could be one potential characteristic for metastatically relevant phenotypes of disseminated tumor cells. An immunocytochemical double staining for uPA-R and CK18 (immunogold/alkaline phosphatase anti-alkaline phosphatase) was performed on perioperative and follow-up bone marrow aspirations of 78 curatively resected gastric cancer patients, if positive tumor cell status had been shown previously with the single alkaline phosphatase anti-alkaline phosphatase method. Bone marrow cells (10(6)) were examined in each assay. Postoperative qualitative and quantitative development of uPA-R-expressing disseminated tumor cells was followed in relation to uPA-R-negative cells and correlated with later clinical relapse. Double staining could be performed perioperatively or in follow-up, or both, in 58 of 78 patients. Expression of uPA-R on perioperatively disseminated tumor cells significantly correlated with later quantitative increases of tumor cells (P = 0.0009). Overall median tumor cell numbers with uPA-R expression significantly increased during follow-up from a median value of 5.5 to 10.0 in 10(6) cells (P = 0.008), and the mean relative percentage of uPA-R-positive, compared with uPA-R-negative, disseminated tumor cells also increased, from 47.9% at surgery to 68.6% in follow-up (P < 0.001). This was mainly due to patients with later tumor relapse (increase from 63.9 to 80.7%, P = 0.001). Patients without relapse showed slight increases at lower percentage levels (5.7% at surgery, 7.4% in follow-up). Differences for relapsing patients were significant (surgery, P = 0.006; follow-up, P < 0.001). Our results suggest from an in vivo model that uPA-R may be one antigen that enables identification and follow-up observations of metastatically relevant phenotypes of disseminated

Topics: Adult; Aged; Aged, 80 and over; Biopsy, Needle; Bone Marrow; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasm Metastasis; Neoplasm, Residual; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Stomach Neoplasms

Determining the prognosis of gastric cancer is the most crucial step in the treatment process. Cytokeratins are intermediate filaments found in the intracellular structure of epithelial tissues. Recent researches have focused on determining the relationship between the expression of cytokeratins and the degree and prognosis of tumors. This study aimed to investigate the relationship between the incidence of cytokeratin-20 and cytokeratin-7 in patients with gastric carcinoma with factors influencing the prognosis. In this regard, the study was conducted cross-sectional. The expression of cytokeratin-20 and cytokeratin-7 was evaluated on 50 gastric adenocarcinoma specimens with different degrees of differentiation by the immunohistochemical method. We determined the relationship between the incidence of cytokeratin-20 and cytokeratin-7 with factors affecting the prognosis of patients, including the degree of differentiation of gastric cancer tissue, lymph node involvement, and the depth of tumor invasion. Data were statistically analyzed by Chi-square and Spearman tests. The results showed a statistically inverse relationship between the incidence of cytokeratin-20 and cytokeratin-7 with the degree of tissue differentiation and lymph node involvement in gastric cancer. Although there was a statistically significant relationship between the incidence of tissue invasion in gastric cancer and the incidence of cytokeratin-7, there was no association between the incidence of cytokeratin-20 and tissue invasion. In general, decreased cytokeratin-20 and cytokeratin-7 are associated with decreased tissue differentiation and increased lymph node involvement.

Topics: Cross-Sectional Studies; Humans; Keratin-20; Keratin-7; Keratins; Neoplasm Invasiveness; Prognosis; Stomach Neoplasms

The tumor-stroma ratio (TSR) determined by pathologists is subject to intra- and inter-observer variability. We aimed to develop a computational quantification method of TSR using deep learning-based virtual cytokeratin staining algorithms. Patients with 373 advanced (stage III [n = 171] and IV [n = 202]) gastric cancers were analyzed for TSR. Moderate agreement was observed, with a kappa value of 0.623, between deep learning metrics (dTSR) and visual measurement by pathologists (vTSR) and the area under the curve of receiver operating characteristic of 0.907. Moreover, dTSR was significantly associated with the overall survival of the patients (P = 0.0024). In conclusion, we developed a virtual cytokeratin staining and deep learning-based TSR measurement, which may aid in the diagnosis of TSR in gastric cancer.

Topics: Adult; Aged; Carcinoma; Deep Learning; Female; Follow-Up Studies; Gastrectomy; Humans; Image Processing, Computer-Assisted; Kaplan-Meier Estimate; Keratins; Male; Middle Aged; Neoplasm Staging; Observer Variation; Risk Assessment; ROC Curve; Stomach; Stomach Neoplasms; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascites; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Female; Gastroscopy; Gene Expression; Humans; Keratins; Lymphatic Metastasis; Membrane Proteins; Middle Aged; NF-KappaB Inhibitor alpha; Stomach; Stomach Neoplasms; Tomography, X-Ray Computed

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

The phenotypic heterogeneity of circulating tumor cells (CTC) in peripheral blood and disseminated tumor cells (DTC) in bone marrow is an important constraint for clinical decision making. Here, we investigated the implications of two different subpopulations of these cells in gastric cancer (GC).. GC patients (n = 228) who underwent elective gastric resections were prospectively examined for CTC/DTC. The cells obtained from peripheral blood and bone marrow aspirates were sorted by flow cytometry and CD45. CD44

Topics: Adult; Aged; Biomarkers, Tumor; Bone Marrow; Disease-Free Survival; Female; Humans; Hyaluronan Receptors; Keratins; Male; Middle Aged; Neoplastic Cells, Circulating; Prognosis; Stomach Neoplasms

Few data are available regarding the epithelial to mesenchymal transition (EMT) /mesenchymal to epitheilal transition (MET) in the liver metastasis of digestive cancers. The aim of this study was to establish EMT/MET metastatic tumor cell plasticity according to the histological growth pattern of liver metastases.. Biopsies from 25 patients with liver metastasis (desmoplastic, replacement and pushing type) were evaluated. Double immunostaining of E-cadherin/vimentin, keratin 8,18/vimentin and E-cadherin/ keratin 8,18 were performed.. The following cell types were noted: epithelial, mesenchymal, non-differentiated and differentiated hybrid mesenchymal/ epithelial and non-hybrid phenotype. All cases had mesenchymal/ epithelial phenotype cells. A significant correlation was found between the non-differentiated hybrid mesenchymal/ epithelial phenotype metastatic cells and histological growth pattern for gastric and colorectal cancer.. A MET-targeting strategy, in conjunction with conventional chemotherapy, may be useful for the treatment of liver metastases.

Topics: Antigens, CD; Cadherins; Cell Plasticity; Colorectal Neoplasms; Digestive System Neoplasms; Epithelial-Mesenchymal Transition; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Vimentin

The aim of this study was to verify if positive results yielded with conventional cytology and immunocytochemical analysis of peritoneal washes correlate with established prognostic factors and overall survival (OS) in gastric cancer patients.. The study included the data of 271 gastrectomized patients. Peritoneal washes of 131 (48.3%) patients were examined by means of conventional cytology, and material from 140 (51.7%) subjects treated surgically after this date was subjected to immunocytochemical analysis.. Free cancer cells (FCCs) were detected significantly less often in patients from conventional cytology group than in those from immunocytochemistry group (4.6% vs. 12.1%). Positive result of immunocytochemical analysis was significantly more often associated with presence of pT3/4 tumor (94.1% vs. 60.2%), lymph node ratio ≥0.2 (82.4% vs. 43.1%) and involvement of blood vessels (64.7% vs. 28.5%). Median OS in patients with immunocytochemical evidence of FCCs in peritoneal washes was significantly shorter than in those without (11 vs. 45 months). Moreover, the two groups differed significantly in terms of 5- (0% vs. 43.1%) and 10-year OS rates (0.0% vs. 29.3%).. In contrast to conventional cytology, immunocytochemically documented presence of FCCs in peritoneal washes correlates with established prognostic factors and OS in gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cytological Techniques; Female; Gastrectomy; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Lymph Node Excision; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Peritoneal Lavage; Peritoneal Neoplasms; Proportional Hazards Models; Stomach Neoplasms

We report a case of vimentin-positive early gastric adenocarcinoma arising in a hyperplastic polyp (HP). A 72-year-old Japanese man was admitted for the detailed examination of a gastric polyp. He had a subtotal gastrectomy due to acute abdomen 12 years ago. Upper endoscopy revealed a pedunculated polyp measuring approximately 2 cm on the greater curvature of upper body of the remnant stomach. Magnifying endoscopy revealed that the microsurface pattern was irregular and partially absent accompanied with irregular microvessels at the upper end of the polyp. We speculated that the lesion was an adenocarcinoma arising in the HP. Endoscopic submucosal dissection (ESD) was performed. Histological examination of the ESD specimen revealed that the lesion consisted of well- to poorly differentiated adenocarcinoma at the protruding lesion and foveolar hyperplastic epithelia at the base of the polyp. Immunohistochemically, most of tumor cells that comprised poorly-differentiated adenocarcinoma were positive for both cytokeratin and vimentin. Although carcinomas have occasionally been found in HPs, the histological features of the present case are considered extremely unusual. To the best of our knowledge, this is the first case of vimentin-positive early gastric carcinoma arising in a HP.

Topics: Adenocarcinoma; Aged; Endoscopic Mucosal Resection; Humans; Hyperplasia; Keratins; Male; Polyps; Stomach Diseases; Stomach Neoplasms; Vimentin

Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas (OSCC) correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines. Krt76

Topics: 5'-Nucleotidase; Animals; Antigens, CD; Apyrase; Cell Line, Tumor; Female; Flow Cytometry; Fluorescent Antibody Technique; Humans; In Situ Hybridization, Fluorescence; In Vitro Techniques; Keratins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mouth Neoplasms; Stomach Neoplasms; T-Lymphocytes, Regulatory

Topics: Aged; Hematopoietic Stem Cell Transplantation; Humans; Intermediate Filaments; Keratins; Leukemia, Myeloid, Acute; Male; Sarcoma, Myeloid; Stomach Neoplasms; Transplantation, Homologous

Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Crohn Disease; Duodenal Neoplasms; Female; Humans; Ileal Neoplasms; Jejunal Neoplasms; Keratins; Male; Metaplasia; Middle Aged; Mucins; Stomach Neoplasms

Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding.. Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections.. Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26-3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation.. Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Proliferation; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Receptor, trkB; Stomach Neoplasms; Young Adult

Topics: Aged; Carcinoma, Adenosquamous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Stomach Neoplasms

Sarcomatoid carcinoma is an uncommon biphasic malignant tumor of the stomach. The histogenesis remains unknown, and a definitive diagnosis is obtained with immunohistochemical staining. Since prognosis is poor after surgery, more effective diagnostic tools are needed in order to select the optimal therapeutic approach. We report the case of an old female patient presenting with an endophytic tumor in the gastric fundus who underwent partial resection of the stomach. Histology revealed a poorly differentiated adenocarcinoma component mixed with sarcomatoid component. Immunohistochemically, the carcinoma components exhibited a positive reaction to pan-cytokeratin, whereas fusiform cells showed positive reactions to vimentin.

Topics: Adenocarcinoma; Aged, 80 and over; Female; Gastrectomy; Humans; Keratins; Stomach Neoplasms; Vimentin

Spindle cell carcinoma (SpCC) is a rare tumor consisting of spindle cells which express cytokeratin. Despite recent advances in immunohistochemical and genetic studies, precise histogenesis of SpCC is still controversial and this tumor had been referred to with a wide range of names (in the past): carcinosarcoma, pseudosarcoma, sarcomatoid carcinoma, pseudosarcomatous carcinoma, and collision tumor. Recently, the authors experienced an extremely rare case of SpCC arising from the stomach. A 64-year-old male presented with unintended weight loss and hematochezia. Endoscopic examination revealed a fistulous tract between the stomach and the transverse colon which was made by direct invasion of SpCC of the stomach to the colon. Histologically, the tumor was positive for both vimentin and cytokeratin but negative for CD117, CD34, actin, and desmin. Herein, we report a case of SpCC arising from the stomach that formed a fistulous tract with the colon which was diagnosed during evaluation of hematochezia and weight loss.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma; Colon, Transverse; Endoscopy, Digestive System; Fistula; Gastrointestinal Hemorrhage; Humans; Keratins; Magnetic Resonance Imaging; Male; Middle Aged; Stomach Neoplasms; Tomography, X-Ray Computed; Weight Loss

Malignant tumors represent one of the most important medical problems, due to the increased mortality rate, life quality alteration, and the lack of a curable treatment. Skin neoplasm ranks first most frequent top primary tumor, summing a higher percentage than any other neoplastic location. It is also known, the fact that, in our country, gastric adenocarcinoma represents the most encountered tumor of the digestive tube. Our case, male, 49-year-old, comes from a rural area, was diagnosed with and surgically treated, within one year, for gastric adenocarcinoma (intestinal type gastric carcinoma) and squamous cell carcinoma (at the level of the lower lip). A high number of etiologic agents are associated with different risks in developing a carcinoma with squamous cells at the level of the head and the neck, and a gastric carcinoma (our patient is known to suffer from gastric ulcer and Helicobacter pylori, for more than 20 years, and he is a chronic consumer of alcohol and nicotine).

Topics: Carcinoma, Squamous Cell; Humans; Keratins; Male; Middle Aged; Mucins; Postoperative Care; Stomach Neoplasms

Gastric cancer has been identified as a target for sentinel lymph node (SLN) navigational surgery. Although accurate evaluation of SLNs is essential for applying the SLN concept to gastric cancer surgery, there is no standardized pathologic examination protocol for SLNs in gastric cancer.. A total of 231 SLNs from 69 patients with cT1-2, N0 gastric cancer were prospectively examined in this study. During the operation, SLNs were sliced at 2-mm intervals, and frozen sections were analyzed by hematoxylin and eosin (HE) staining in 35 patients or HE staining with rapid immunohistochemistry (IHC) for pancytokeratin (CK) in 34 patients. HE staining and CK IHC were performed postoperatively on each remaining SLN. Non-SLNs were evaluated with 2 levels of HE slides and 1 CK IHC.. Of 35 patients, metastasis was identified in 10 patients by intraoperative HE staining, and in 12 patients by postoperative HE staining and CK IHC. Two patients had isolated tumor cells (ITCs) detectable by postoperative CK IHC; these patients had non-SLN metastasis. We enrolled another 34 patients and examined 147 SLNs by frozen HE and rapid IHC. In this cohort, 26 patients with negative SLNs by intraoperative examination did not have non-SLN metastasis even after deeper sectioning and CK IHC of non-SLNs (sensitivity, 100%; false negative value, 0%).. Our study indicated that precise and detailed intraoperative examination decreases the false-negative rate of SLN biopsy. ITCs in SLNs should not be overlooked, and rapid IHC can be helpful for detecting ITCs intraoperatively.

Topics: Aged; Aged, 80 and over; Blood Stains; False Negative Reactions; Female; Frozen Sections; Hematoxylin; Humans; Immunohistochemistry; Intraoperative Period; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Sentinel Lymph Node Biopsy; Sentinel Surveillance; Stomach Neoplasms

Described is a novel real-time multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay suitable for intraoperative detection of micrometastasis (MM) in sentinel nodes (SNs) dissected from patients with clinical N0 (cN0) gastric carcinoma.. One hundred three patients with gastric cancer, who were preoperatively diagnosed with cN0 and clinical T1 or T2, were enrolled. The patients underwent SN mapping followed by standard radical gastrectomy with lymph node dissection. In addition to all SNs, non-SNs (NSNs) within the SN lymphatic basin and NSN from a different lymphatic basin were randomly sampled. All SNs and NSNs were examined by routine histologic diagnosis and RT-PCR for the expression of cytokeratin (CK) 19, CK20, and carcinoembryonic antigen (CEA).. The RT-PCR assay and histologic examination were performed in 512 SNs and 299 NSNs from 103 patients. Pathologic l lymph node metastasis was revealed in 13 (12.6%) of 103 patients. All metastatic lymph nodes were identified within SNs. SNs of these 13 patients had positive findings on RT-PCR. Twenty-eight (27.2%) of 103 patients had negative histopathology but positive findings on RT-PCR. In 7 patients (6.8%), SNs were negative but NSNs were positive on RT-PCR. RT-PCR-positive NSNs were present in the same station as corresponding SNs in 3 of these 7 patients and in the same basin as SNs in 4 patients.. The real-time multiplex RT-PCR assay is a useful tool for the detection of MM in SNs and NSNs in patients with gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Follow-Up Studies; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Micrometastasis; Neoplasm Staging; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Survival Rate

(1) To test whether in genomewide expression profiling differentially expressed genes were also distinct on the protein level including KIT and PDGFRA (2) to correlate the expression with clinicopathological parameters (3) to identify activating mutations that might be eligible for tyrosine kinase inhibitor therapy by mutational analysis of tumors with high expression.. Gastroenteropancreatic neuroendocrine tumors (GEP NETs) from 119 patients were analyzed for protein expression of ten biomarkers. Mutational analysis of KIT (exon 9, 13, 11 and 17) and PDGFRA (exons 12 and 18) was performed on those samples that showed high protein expression.. High KIT expression was observed in 13% of all specimens, PDGFRA in 33%, CK19 in 26%, CK7 in 2%, CK20 in 5%, S100 in 6%, CD56 in 25%, Chromogranin in 55%, and Synapthophysin in 80%. High expression of KIT and PDGFRA was significantly correlated with shorter disease-specific survival (P = 0.003, P = 0.018, respectively). In multivariate analysis expression of PDGFRA, radicality of surgical treatment and WHO grading influenced disease-specific 10-year survival independently (P = 0.032, P = 0.001 and P = 0.008, respectively). Mutational analysis of highly expressed specimens (n = 51) reveals a novel mutation of KIT in exon 11 (K558N_V559insP) in a well-differentiated metastatic pancreatic neuroendocrine tumor.. High expression of KIT and PDGFRA was significantly correlated with shorter patients survival and could serve as prognostic marker. Mutations of the KIT gene might open new avenues for tyrosine kinase inhibitor therapy in a subset of patients with advanced pancreatic neuroendocrine tumors.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CD56 Antigen; Chromogranin A; Digestive System Neoplasms; DNA Mutational Analysis; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intestinal Neoplasms; Kaplan-Meier Estimate; Keratins; Ki-67 Antigen; Male; Middle Aged; Mutation; Neuroendocrine Tumors; Odds Ratio; Pancreatic Neoplasms; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; S100 Proteins; Stomach Neoplasms; Synaptophysin; Up-Regulation

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the molecular basis that determines variations in CK patterns in gastric cancers (GCs). The aim of the present study was to analyze the CK expression patterns in a large number of GCs and to investigate how the CK patterns correlate with clinicopathologic parameters, histology, mucin phenotype or several tumor-related molecules.. We immunohistochemically examined the CK7/CK20 patterns, mucin expression profiles (MUC5AC, MUC6, MUC2 and CD10), and the cancer-related molecules (CDX2, p53, EGFR and β-catenin), using a tissue microarray with 870 GCs. The GCs were divided into four patterns; 17% of CK7+/CK20+, 57% of CK7+/CK20-, 9% of CK7-/CK20+ and 17% of CK7-/CK20. GCs with the CK7-/CK20- pattern demonstrated a close relation to undifferentiated adenocarcinoma. CK7 expression was significantly correlated with the expression of MUC5AC and MUC6, while CK20 expression was correlated with MUC2 and CDX2. There were statistically significant associations between CK expression patterns and mucin phenotypes.. These results indicate that the CK7/CK20 expression patterns in GCs demonstrated different clinicopathologic features and molecular signatures.

Topics: Biomarkers, Tumor; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Keratins; Mucin 5AC; Mucin-2; Mucin-6; Mucins; Neprilysin; Stomach Neoplasms

Topics: Aged; Carcinoma, Medullary; Epstein-Barr Virus Infections; Gastric Mucosa; Gastroscopy; Humans; Immunohistochemistry; Keratins; Male; Stomach Neoplasms; Ultrasonography

Adenosquamous carcinoma originating in the stomach is an unusual neoplasm with few existing histological studies. This study was aimed to gain insight into the histogenetic and clinicopathological characteristics of gastric cancer with squamous cell carcinoma (SCC) components.. From January 2001 to June 2010 a total of 1735 patients underwent a resection of gastric cancer. Histopathologically, eight patients had adenocarcinoma containing SCC components, in which the proportion of SCC components was above 25% of the total tumor mass in four patients. The immunohistochemical and clinicopathological characteristics of these eight patients were analyzed.. The median survival duration was 22 months. Adenocarcinoma was present at the superficial layer of all tumors and SCC was primarily present at sites with deep invasion. Immunohistochemically, adenocarcinoma components were positive for cytokeratin (CK) 8/18/19 and CK7 in all cases. SCC components were positive for carcinoembryonic antigen and CK7 in more than 60% of patients. Expression patterns of p53 product were identical in both components. SCC components were positive for 34βE12 and adenocarcinoma components were negative for 34βE12 in all patients.. SCC components are derived from squamous metaplasia in a pre-existing adenocarcinoma. A gastric adenocarcinoma with SCC components is associated with various patterns of metastasis and both SCC and adenocarcinoma components have the potential for metastasis. Gastric cancer with SCC components is a clinically aggressive tumor.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Cadherins; Carcinoembryonic Antigen; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratin-18; Keratin-19; Keratin-7; Keratin-8; Keratins; Ki-67 Antigen; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tumor Suppressor Protein p53

Altered cell motility is considered to be a key factor in determining tumor invasion and metastasis. Epidermal growth factor (EGF) signaling has been implicated in this process by affecting cytoskeletal organization and dynamics in multiple ways. To sort the temporal and spatial regulation of EGF-dependent cytoskeletal re-organization in relation to a cell's motile behavior time-lapse microscopy was performed on EGF-responsive gastric carcinoma-derived MKN1 cells co-expressing different fluorescently labeled cytoskeletal filaments and focal adhesion components in various combinations. The experiments showed that EGF almost instantaneously induces a considerable increase in membrane ruffling and lamellipodial activity that can be inhibited by Cetuximab EGF receptor antibodies and is not elicited in non-responsive gastric carcinoma Hs746T cells. The transient cell extensions are rich in actin but lack microtubules and keratin intermediate filaments. We show that this EGF-induced increase in membrane motility can be measured by a simple image processing routine. Microtubule plus-ends subsequently invade growing cell extensions, which start to accumulate focal complexes at the lamellipodium-lamellum junction. Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. These adhesions then serve as nucleation sites for keratin filaments which are used to enlarge the neighboring peripheral keratin network. Focal adhesions are either disassembled or give rise to stable zyxin-rich fibrillar adhesions which disassemble in the presence of EGF to support formation of new focal adhesion sites in the cell periphery. Taken together the results serve as a basis for modeling the early cytoskeletal EGF response as a tightly coordinated and step-wise process which is relevant for the prediction of the effectiveness of anti-EGF receptor-based tumor therapy.

Topics: Actins; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma; Cell Movement; Cetuximab; Epidermal Growth Factor; ErbB Receptors; Focal Adhesions; Gene Expression; Humans; Keratins; Microtubules; Paxillin; Phosphorylation; Pseudopodia; Signal Transduction; Stomach Neoplasms; Time Factors; Time-Lapse Imaging; Tumor Cells, Cultured; Zyxin

Topics: Antibodies, Monoclonal; Biomarkers; Clinical Trials, Phase III as Topic; Humans; Keratin-18; Keratin-8; Keratins; Randomized Controlled Trials as Topic; Stomach Neoplasms

Topics: Biopsy; Carcinoma, Signet Ring Cell; Cicatrix; Fatal Outcome; Humans; Keratins; Linitis Plastica; Male; Middle Aged; Pulmonary Embolism; Skin Neoplasms; Stomach Neoplasms

Topics: Antibodies, Monoclonal; Biomarkers; Humans; Keratin-18; Keratin-8; Keratins; Lymph Nodes; Lymphatic Metastasis; Stomach Neoplasms

Topics: Aged; Antigens, CD; Carcinoma; Diagnosis, Differential; Diagnostic Errors; Gastrectomy; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Keratins; Male; Stomach Neoplasms

We report on a patient with obstructive jaundice caused by recurrence of gastric carcinoma in the wall of an extrahepatic bile duct more than 5 years after gastrectomy who was treated with pancreaticoduodenectomy. Histopathologic examination of the surgically resected specimen revealed a poorly differentiated adenocarcinoma with focal signet ring cells in the wall of the common bile duct which was histologically similar to the primary gastric carcinoma. To confirm the diagnosis, immunohistochemical staining was performed with antibodies against cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC5AC, MUC6, MUC2). Based on the expression patterns of this monoclonal antibody panel, the final diagnosis of the common bile duct tumor was an isolated local recurrence of the gastric carcinoma. The patient has survived for more than 26 months after pancreaticoduodenectomy without recurrence.

Topics: Bile Ducts, Extrahepatic; Carcinoma; Female; Humans; Immunohistochemistry; Jaundice, Obstructive; Keratins; Medical Oncology; Middle Aged; Mucins; Pancreaticoduodenectomy; Recurrence; Stomach Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

Micropapillary carcinoma (MPC) of the stomach is a rare, newly recognized entity, and only 2 patients with this histology have been reported. We investigated clinicopathologic features, expression of mucin (MUC2, MUC5AC, MUC6, CD10) and cytokeratin profiles (CK7 and CK20), epidermal growth factor receptors (EGFR and HER2), prognostic markers (p53 and Ki-67), and outcomes in 11 MPCs of the stomach. The proportion of MPC component ranged from 5% to 70%. Micropapillary features were often found at the deep advancing edge of the tumor. Endolymphatic tumor emboli were found in 10 cases (91%) and lymph node metastases were found in 4 cases (36%). In MPCs, positive expression was observed for Ki-67 (82%), CK7 (73%), EGFR (64%), p53 (64%), MUC5AC (45%), MUC6 (36%), and CK20 (27%). However, MUC2, CD10, and HER2 expression was negative in all cases. In 9 conventional adenocarcinomas and 11 papillary adenocarcinomas with multiple endolymphatic tumor emboli, used as control, positive expression was observed for Ki-67 (100%), CK7 (90%), EGFR (80%), CK20 (70%), p53 (70%), MUC5AC (70%), MUC6 (60%), MUC2 (40%), CD10 (25%), and HER2 (15%). Expression of MUC2, CK20, and the Ki-67 labeling index was significantly higher in control adenocarcinomas as compared with MPCs (P<0.05). However, there was no significant difference in other clinicopathologic features and overall patient survival. Subclassification of MPCs into 2 subgroups according to the proportion of micropapillary component (cut-off value was 20%) failed to find any significant clinicopathologic differences (P>0.05). Although MPCs in other organs show a poor prognosis, this does not seem to be true for gastric MPCs. Further larger studies are necessary to confirm our initial findings.

Topics: Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Aged; Aged, 80 and over; Biomarkers, Tumor; ErbB Receptors; Female; Gastric Mucins; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Ki-67 Antigen; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Receptor, ErbB-2; Republic of Korea; Stomach Neoplasms; Time Factors; Treatment Outcome; Tumor Suppressor Protein p53

The clinical significance of isolated tumor cells (ITC) detected immunohistochemically in the lymph nodes of gastric cancer patients is controversial. The aim of this study was to examine the prognostic impact of ITC in patients with gastric cancer.. The data of a total of 402 patients with pathological T2N0 and T2N1 gastric cancer who underwent gastrectomy with D2 lymph node dissection between 1984 and 1990 at four participant hospitals were analyzed. All resected lymph nodes were reexamined by serial sectioning with hematoxylin & eosin (H&E) staining, and evaluated by immunohistochemistry using antibody against cytokeratin (AE1/3). The prevalence and prognostic significance of ITC were investigated.. ITC were detected in 187 of the 402 (47%) patients. A multivariate analysis identified the nodal status, histological type, and tumor size as significant factors predictive of the presence/absence of ITC. The 5-year and 10-year overall survival rates of patients with vs those without ITC were 84.4% (95% confidence interval [CI], 79.1-89.0) and 70.4% (95% CI, 64.1-76.7) vs 83.9% (95% CI, 78.6-89.2) and 72.0% (95% CI, 65.4-78.5), respectively. The hazard ratio for death in patients with ITC as compared with those without ITC was 0.90 (95% CI, 0.64-1.26; P = 0.53).. The presence of ITC in the lymph nodes does not affect the prognosis of patients with gastric cancer who have undergone gastrectomy with D2 lymph node dissection.

Topics: Biomarkers, Tumor; Confidence Intervals; Female; Gastrectomy; Humans; Immunohistochemistry; Japan; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Analysis; Ultrasonography

Topics: Adenocarcinoma; Aged; Female; Gastrectomy; Gastrointestinal Stromal Tumors; Humans; Keratins; Neoplasms, Multiple Primary; Proto-Oncogene Proteins c-kit; Stomach Neoplasms

Topics: Biomarkers, Tumor; Humans; Keratins; Male; Middle Aged; Neoplasm Proteins; Skin Neoplasms; Stomach Neoplasms

The clinical significance of immunohistochemically detected isolated tumor cells (ITC) in lymph nodes of gastric cancer patients is controversial. This study examined the prognostic impact of ITC on patients with early-stage gastric cancer in two large volume centers in the United States and Japan.. Fifty-seven patients with T2N0M0 gastric carcinoma who underwent gastric resection between January 1987 and January 1997 at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and 107 patients resected at National Cancer Center Hospital (NCCH) in Tokyo between January 1984 and December 1990 were studied. The sections were newly prepared from each lymph node for immunohistochemical staining for cytokeratin. Lymph nodes and original specimens from MSKCC were examined by pathologists in NCCH. The prognostic significance of the presence of ITC in lymph nodes was investigated in patients of both institutions.. ITC were identified in 30 of 57 patients (52.6%) at MSKCC and in 38 of 107 patients (35.5%) at NCCH. In both institutions, there was no significant difference in the prognosis of the studied patients with or without ITC (P= .22, .86 respectively).. The presence of ITC detected by immunohistochemistry in the regional lymph nodes did not affect the prognosis of American and Japanese patients with T2N0M0 gastric carcinoma who underwent gastrectomy with D2 lymph node dissection.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Differentiation; Female; Follow-Up Studies; Gastrectomy; Humans; Immunoenzyme Techniques; Japan; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplastic Cells, Circulating; Prognosis; Risk Factors; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Survival Rate; United States

Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate the expression of EMT-related proteins in gastric carcinoma (GC).. The expression of nine EMT-related proteins in the GC tissues of 598 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed in GC. These protein alterations were associated with diffuse type histology, advanced stage and poor patient outcome, respectively. Subjects were divided into three groups according to degree of EMT-related protein alteration. Increases in alteration of EMT-related protein were found to be significantly associated with poorly differentiated histology, higher pTNM stage and unfavourable outcome. Multivariate analysis showed that alterations in the expression of EMT-related proteins were independently associated with poor prognosis.. Loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with poorly differentiated histology, advanced stage and poor outcome in GC. The awareness and inhibition of EMT offer a promising target for prevention of metastatic progression and invasion.

Topics: Cadherins; Catenins; Epithelium; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Keratins; Male; Matrix Metalloproteinase 2; Mesoderm; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Prognosis; S100 Calcium-Binding Protein A4; S100 Proteins; Snail Family Transcription Factors; Stomach Neoplasms; Tissue Array Analysis; Transcription Factors; Vimentin

The chemokine receptors CCR7 and CXCR4 play a major role in the mechanism of lymph node metastasis from primary tumor cells. We postulated that their expression in gastric tumor cells could predict lymph node status including lymph node micrometastasis (LNMM). We assessed CCR7 and CXCR4 expression in 93 resected gastric tumor specimens by immunohistochemistry. Dissected lymph nodes were examined by reverse transcription-polymerase chain reaction and immunohistochemistry using cytokeratin monoclonal antibody to detect LNMM in addition to hematoxylin-eosin (H&E) staining. Levels of CCR7 and CXCR4 expression were high in 26.9% (25/93) and in 32.3% (30/93), respectively of tumor cells and the levels significantly correlated with lymph node metastasis according to H&E staining (P=0.0212 and P=0.0115, respectively). We identified LNMM in 25 of 83 (30.1%) node-negative patients. Both CCR7 and CXCR4 expression significantly correlated with lymph node status including LNMM (P=0.0092 and P=0.0075, respectively). Furthermore, levels of combined CCR7 and CXCR4 expression significantly correlated with lymph node metastatic status (P=0.0021). Assessment of CCR7 and CXCR4 expression in gastric cancer is a useful tool for predicting lymph node metastatic status including LNMM.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Line, Tumor; Female; Gastrectomy; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Receptors, CCR7; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms

This report describes 3 cases of a distinctive, hitherto unreported gastric epitheliomesenchymal biphasic tumor that differs from other biphasic tumors of the stomach and elsewhere: carcinosarcoma, biphasic synovial sarcoma, teratoma, and mixed tumor. The tumors occurred in young adults, 2 males and 1 female, of ages 19, 27, and 30 years. Two tumors were located in the greater curvature in the gastric body and one in the antrum. The tumors measured 5, 6, and 15 cm in maximum diameter, and their mitotic rates were 0, 4, and 30 mitoses per 50HPF. There were 2 components: uniform oval or spindled cells in diffuse sheets, and clusters or cords of epithelial cells occasionally forming glandular structures with small lumens. The epithelial elements were positive for keratin cocktail AE1/AE3, keratin 18, and partly for keratin 7, but were negative for keratins 5/6, 20 and epithelial membrane antigen. The spindle cells were positive for vimentin and CD10. All components were negative for CD34, CD99, estrogen receptor, KIT, smooth muscle actin, desmin S100 protein, p63, calretinin, chromogranin, synaptophysin, CDX2, and thyroid transcription factor 1. In situ hybridization for SS18 rearrangement was negative in all cases separating this tumor from synovial sarcoma. All 3 patients were alive after follow-up of 3.5, 5, and 14 years. Because these tumors have some resemblance to blastomas of other organs, we propose the term "gastroblastoma" for this distinctive, at least low-grade malignant epitheliomesenchymal tumor of the stomach.

Topics: Adult; Biomarkers, Tumor; Carcinosarcoma; Disease-Free Survival; DNA, Neoplasm; Female; Gastrectomy; Humans; In Situ Hybridization, Fluorescence; Keratins; Male; Neoplasms, Complex and Mixed; Neprilysin; Stomach Neoplasms; Treatment Outcome; Vimentin; Young Adult

The patient was a 75-year-old man whose complaint was back pain and appetite loss. He was diagnosed with unresectable advanced gastric cancer due to multiple liver metastases and direct invasion of pancreas and spleen. He underwent gastrostomy because of esophageal stenosis, and we administered S-1 80 mg/body(4 weeks administration and 2 weeks rest)to the patient through a gastrostogavage tube. On blood examination, the serum level of CYFRA21- 1 was significantly high, while those of CEA and CA19-9 were within normal ranges. After the first course of this chemotherapy, the serum CYFRA21-1 level significantly decreased with reduction of the cancer. After the second course, it sensitively increased before image views detected the progression of the cancer. This case shows that CYFRA21- 1 could be a useful tumor marker of advanced gastric cancer.

Topics: Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Gastroscopy; Humans; Keratin-19; Keratins; Male; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Failure

The 6th edition of the TNM classification has recently defined "sentinel nodes (SN)," "micrometastasis," and "isolated tumor cells (ITC)." The present study examines the frequency and proliferative activity of such metastases with focus on the SNs of gastric cancer.. We enrolled 133 patients with cT1-2 tumors (cT1: 104, cT2: 29) and mapped SNs. Lymph node metastases were examined by routine histology and by immunohistochemistry with anti-cytokeratin. We used the Ki-67 antibody to detect the primary tumor and lymph node metastases to evaluate proliferative activity.. The number of patients with SNs metastases and metastatic SNs was 19 and 52, respectively. The frequencies of macrometastasis, micrometastasis, and ITC were 48%, 25%, and 27%, respectively. Ki-67 expression in the tumor closely correlated with lymphatic invasion (P = 0.0001), venous invasion (P < 0.0001), and lymph node metastasis (P < 0.0001). Cells in 96% of macrometastases, 92% of micrometastases, and 29% of ITCs were Ki-67 positive.. We showed that micrometastasis and some ITCs in SNs had proliferative activity. We suggest that micrometastasis and ITCs should be removed, especially during SN navigation surgery, until their clinical significance is clarified.

Topics: Carcinoma; Cell Differentiation; Cell Division; Gastrectomy; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Sentinel Lymph Node Biopsy; Stomach Neoplasms

To determine the prognostic significance of the methods used to determine the presence of metastasis in second-tier lymph nodes of patients with gastric cancer, the authors studied lymph nodes surgically removed from 100 patients with gastric cancer (55 with early cancer, 45 with progressive). The results of HE staining were compared with those of immunohistochemistry using the anticytokeratin (CK) antibody and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. Lymph node 7 or 8a was obtained intraoperatively, then mRNA was extracted using an immunobeads method, and RT-PCR with CK19 mRNA was performed. The P for Cox regression analysis for metastasis detected by HE staining, CK staining, and RT-PCR of all 100 cases was 0.312, 0.426, and 0.021, respectively, while for second-tier lymph nodes it was 0.154, 0.013, and 0.006, respectively. In conclusion, RT-PCR and CK staining for detection of metastasis in second-tier lymph nodes were more reliable prognostic indicators than conventional HE staining.

Topics: Aged; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Staining and Labeling; Stomach Neoplasms; Survival Analysis

Recently, micrometastasis (MM) in the lymph node in gastric cancer has been detected by cytokeratin immunostaining. However, clinical significance of MM and its relationship with reduced expression of E-cadherin in primary lesion have not been well studied.. The 4,990 lymph nodes from 184 pT1~T3N0 patients from 1995 to 2000 at Korea University Hospital were immunostained with the anticytokeratin AE1/3 antibody for detection of micometastasis. The primary lesions were also immunostained for E-cadherin expression.. MM in the lymph node of gastric cancer was found in 131 (2.6%) of total dissected nodes, and 31 of 184 patients (16.8%) were shown to have MM. The MM was significantly correlated with the depth of invasion, tumor size, operation method, Lauren classification, lymphovascular invasion and loss of E-cadherin expression in primary tumor. On multivariate analysis, the independent risk factors for MM were the depth of invasion and loss of E-cadherin expression. The patients with MM had significantly lower 5-year overall and disease free survival rate than those without MM.. Lymph node MM in histologically node-negative gastric cancer was significantly correlated with poor 5-year survival rate. The determination of E-cadherin expression in primary gastric tumor may be useful in prediction of the MM.

Topics: Adenocarcinoma; Cadherins; Disease-Free Survival; Female; Follow-Up Studies; Gastrectomy; Humans; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Stomach Neoplasms; Survival Rate

The detection of isolated (circulating or disseminated) tumour cells (ITC) in patients with cancer requires very sensitive methods, as such cells are very rare. In the present study, the method that combines the negative isolation of CD45- leukocytes from the blood and bone marrow of patients with gastric cancer by flow cytometry, followed by the positive isolation of single cytokeratin-positive (CK+) cells by a Laser Capture Microdissection System for the determination of MAGE-1, -2 mRNA expression was used to detect ITC. This study shows that this method is highly sensitive as it allows to determine beta-actin-mRNA expression in a single CK+ cell. Using > or =5 CK+ cells as a cut-off level, the MAGE-1 mRNA expression was detected in 100% of CK+ cells in the peripheral blood and in 75% of bone marrow samples of patients with gastric cancer. The MAGE-2 mRNA expression was observed in 40 and 58% of samples, respectively. Furthermore, an analysis of primary tumours and locoreginal lymph nodes with respect to the mRNA expression of the two genes showed that MAGE-1 mRNA expression was detected in 88% of the primary tumours and in 67% of the lymph node samples, whereas the MAGE-2 mRNA expression was observed in 72 and 67% of the cases, respectively. Thus, the method described here allows the precise and sensitive determination of tumour-associated gene expression in single ITC present in the blood and bone marrow of patients with gastric cancer.

Topics: Antigens, Neoplasm; Bone Marrow; Cell Separation; Humans; Keratins; Melanoma-Specific Antigens; Neoplasm Proteins; Neoplastic Cells, Circulating; RNA, Messenger; Stomach Neoplasms

In routine practice, gastrointestinal stromal tumor (GIST) can usually be identified with relative ease on the basis of a rather simple immunohistochemical panel besides its characteristic morphology. Still, serious differential diagnostic problems may arise because of the heterogeneity of these tumors in both morphologic appearance and clinical behavior. In our case, we present a metastatic, ulcerative, hemorrhagic GIST with epithelioid appearance, which displayed diffuse pan cytokeratin (AE1/AE3) positivity beside CD117 expression. As carcinomas may also be CD117-positive, definitive diagnosis was confirmed by the detection of a hexanucleotide deletion in the exon 11 of c-kit. This case demonstrates that although gastric carcinoma more commonly ulcerates or causes hemorrhage than GIST, keratin-positive GIST should also be considered from a differential diagnostic point of view. In these cases, c-kit mutation analysis may be necessary.

Topics: Carcinoma; Diagnosis, Differential; DNA Mutational Analysis; Exons; Female; Gastrointestinal Stromal Tumors; Gene Deletion; Humans; Keratins; Middle Aged; Proto-Oncogene Proteins c-kit; Sequence Deletion; Stomach Neoplasms

To explore the effect of advanced gastric cancer on vagniae vasorum of gastric vessels. To provide evidence for the surgical treatment of gastric cancer.. The study included 107 specimens of left and right gastric arteries (55 left and 52 right ) from 59 patients who underwent radical gastrectomy for carcinoma. All specimens were dealt with frozen section method, then they were stained with HE, enzyme histochemical method and immunohistochemical method, respectively.. Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage IV and III specimens. Cytokeratin positive of tumor cells in or on vagina vasorum was showed on 26 slices from 14 tumors. Among them, 4 slices from 2 tumors belonged to stage III, and 22 slices from 12 tumors belonged to stage IV. Observed under light microscope, the lymphatic capillaries within vagina vasorum were dark brown with 5'-nucleotidase staining in 107 specimens, the capillary tubes within vagina vasorum were blue with alkaline phosphatase staining in 101 specimens. The two structures changed with the development of gastric carcinoma. Average area and bulk density of lymphatic vessel vaginae vasorum were associated with TNM staging of gastric cancer (P=0.001 and P=0.004).. Vaginae vasorum dissection, which may not be applied for early gastric cancer, is recommended when clearing lymph nodes around arteries in radical gastrectomy for carcinomas in stage II and above.

Topics: Adult; Aged; Female; Humans; Keratins; Male; Middle Aged; Neoplasm Staging; Stomach; Stomach Neoplasms; Vasa Vasorum

Immunohistochemically detectable isolated tumour clusters (ITCs) with a diameter of less than 0.2 mm have been regarded as non-metastatic lesions, because of a lack of proliferative activity. This study investigated the proliferative activities of ITCs.. Three hundred and eight patients with primary gastric cancer diagnosed as pN0 by routine histological examination were studied. All patients underwent curative resection. Sections of lymph nodes were stained by double-immunostaining methods using anti-cytokeratin and anti-Ki-67 antibody (MIB-1).. ITCs were detected in 77 nodes from 37 patients, designated as having pN0(i+) lesions. Seventy of 77 lymph nodes with ITCs were detected in the N1 station, and seven were found in the N2 station. Of 25 single isolated cancer cells, 12 showed positive labelling with MIB-1, and 49 of 52 ITCs with clusters of cancer cells had positive MIB-1 labelling (mean(s.d.) 46.6(30.1) per cent). Five of the 37 patients with ITCs (pN0(i+)) versus one of the 271 patients with no evidence of ITCs (pN0(i-)) died from recurrence. Patients with ITCs had a significantly worse prognosis than those without (P = 0.014).. ITCs have a high proliferative activity and may have the potential to evolve into established lymph node metastasis.

Topics: Cell Proliferation; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Lymph Nodes; Lymphatic Metastasis; Male; Prognosis; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Survival Analysis

To explore the relationship between metastasis and vagina vasorum in the progress of gastric carcinoma and to find some facts and references for gastric surgeons.. One hundred and seven specimens of left or right gastric arteries (55 left and 52 right) were gathered from 59 patients undergoing radical gastrectomy for gastric carcinoma. All the frozen specimens were cut into 3 microm-thick sections and stained with hematoxylin-eosin (HE) and immunohistochemical method separately. Cytokeratin (CK) and mesothelial cells (MC) were stained with immunohistochemical method. Cancer cells inside vagina vasorum were detected and the structure of artery wall was observed under microscope.. Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage III or IV specimens, but not in stage I or II specimens. Tumor cells in vagina vasorum were CK positive in 26 specimens of 14 tumors. Among them, stage III was found in 4 specimens of 2 tumors, and stage IV in 22 specimens of 12 tumors. None of these specimens was positive for MC. The positive rate of CK increased with TNM staging. Compared with the lower part, tumors in the upper and middle parts of stomach were more likely to metastasize into vagina vasorum.. Vagina vasorum dissection should be performed during D2 lymphadenectomy for TNM stage III or IV gastric carcinoma.

Topics: Adult; Aged; Arteries; Disease Progression; Epithelium; Female; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms; Vasa Vasorum

There are cases of recurrence even after curative resection in early gastric cancer.. Seven hundred and sixty-five patients with early gastric cancer who underwent curative gastrectomy were analyzed to identify the prognostic factor. Micrometastases within lymph nodes were determined by immunohistochemistry using anti-cytokeratin antibody in node-negative early gastric cancer patients with recurrence.. The recurrence was observed in 17 patients. Hematogenous recurrence was observed most frequently (47.1%), followed by peritoneal recurrence (23.5%). Of 17 patients with recurrence, 6 (35.3%) patients died more than 5 years after operation. The prognosis was poorer when the patients were older, and the depth of invasion was greater, lymph node metastasis, lymphatic involvement, and vascular involvement were present, and lymph node dissection was limited. The independent prognostic factors were lymph node metastasis, lymph node dissection, and age by multivariate analysis using Cox proportional hazards. Micrometastases within lymph nodes were confirmed in 3 of 6 node-negative patients with recurrence.. When patients have lymph node metastases or are older, close and long-term follow-up and careful planning of postoperative adjuvant therapy might be necessary to avoid recurrence. The detection of micrometastases by anti-cytokeratin antibody might be useful for predicting the possibility of recurrence in early gastric cancer.

Topics: Adenocarcinoma; Age Factors; Aged; Aged, 80 and over; Female; Follow-Up Studies; Gastrectomy; Humans; Immunoenzyme Techniques; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Peritoneal Neoplasms; Prognosis; Proportional Hazards Models; Stomach Neoplasms

Bone marrow (BM) is a prognostically relevant indicator organ of micrometastasis; however, the clinical importance of BM micrometastasis in gastric cancer patients is not yet known. In the present study, the BM of 267 consecutive patients with primary gastric cancer was examined for tumor cells using immunocytochemical techniques. Real-time quantitative RT-PCR was used to ensure that the tumor cells were detected properly. Among the 267 cases analyzed, 30 cases (11.2%) had cytokeratin-positive cells in the bone marrow. Positive findings were related to the tumor stage (P<0.05) and to the prominent depth of invasion (P<0.05). All patients with liver metastasis at operation had cytokeratin-positive cells in the BM. Recurrence of the disease was confirmed in 50 cases (18.7%); 4 of 30 (13.3%) in the cytokeratin-positive group and 46 of 237 (19.4%) in the cytokeratin-negative group. There were no significant differences in the 5-year survival rates between the cytokeratin-positive and cytokeratin-negative groups. Our study shows that BM micrometastasis increases according to tumor progression; however, only a subset of cancer cells may survive in the BM and finally evolve to a clinically apparent disease. Therefore it does not accurately predict the prognosis or recurrence of the disease.

Topics: Aged; Bone Marrow Cells; Bone Marrow Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplastic Cells, Circulating; Neovascularization, Pathologic; Prognosis; Stomach Neoplasms; Survival Rate

Synchronous tumors of the stomach are uncommon. We present a unique case of gastric synchronous tumors composed of signet-ring cell adenocarcinoma and gastrointestinal stromal tumor (GIST). The two tumors arose at the same site and were sharply juxtaposed without intermingling of morphologically distinct elements. Coincidence probably accounts for this occurrence, even if a common carcinogenic agent had been hypothesized. Preoperative imaging and endoscopic biopsy could lead to the suspicion of synchronous tumors, and an accurate histological identification of both tumors could be achieved by multiple deep endoscopic biopsies. The presence in our case of diffuse carcinomatosis indicates that the signet-ring cell adenocarcinoma had a greater adverse effect on the prognosis than the GIST.

Topics: Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma, Signet Ring Cell; Endoscopy, Gastrointestinal; Gastrointestinal Stromal Tumors; Humans; Keratins; Male; Mucins; Neoplasms, Multiple Primary; Periodic Acid-Schiff Reaction; Stomach Neoplasms; Tomography, X-Ray Computed

Rabbit antibodies may have favorable properties compared to mouse antibodies, including high affinities and better antigen recognition. We used a biochemical and reverse immunologic approach to generate and characterize rabbit anti-phospho-keratin and anti-keratin monoclonal antibodies (MAb). Human keratins 8 and 18 (K8/K18) were used as immunogens after isolation from cells pretreated with okadaic acid or pervanadate to promote Ser/Thr or Tyr hyperphosphorylation, respectively. Selected rabbit MAb were tested by immunofluorescence staining, immunoprecipitation, and 2-dimensional gels. Keratin phospho and non-phospho-mutants were used for detailed characterization of two unique antibodies. One antibody recognizes a K8 G61-containing epitope, an important epitope given that K8 G61C is a frequent mutation in human liver diseases. This antibody binds K8 that is not phosphorylated on S73, but its binding is ablated by G61 but not S73 mutation. The second antibody is bispecific in that it simultaneously recognizes two epitopes: one phospho (K8 pS431) conformation-independent and one non-phospho conformation-dependent, with both epitopes residing in the K8 tail domain. Therefore, a reverse immunologic and biochemical approach is a viable tool for generating versatile rabbit MAb for a variety of cell biologic applications including the potential identification of physiologic phosphorylation sites.

Topics: Animals; Antibodies, Bispecific; Antibodies, Monoclonal; Brain; Brain Chemistry; Cell Line; Colonic Neoplasms; Cricetinae; Enzyme Inhibitors; Epitopes; HT29 Cells; Humans; Immunoblotting; Immunohistochemistry; Keratin-18; Keratin-8; Keratins; Kidney; Liver; Liver Diseases; Mice; Mutation; Okadaic Acid; Phosphorylation; Rabbits; Serine; Stomach Neoplasms; Transfection; Vaccination; Vanadates

The aim of this study was to clarify whether the metastasis of gastric cancer can be detected by identifying the sentinel lymph nodes (SNs) using only lymphatic dye.. The study was based on 101 patients clinically diagnosed with T1 and T2 gastric cancer. Isosulfan blue was intraoperatively injected within the submucosal layer around the lesion through an endoscope and blue stained nodes (BNs) were identified as SNs and harvested. Standard radical gastrectomy with D2 lymphadenectomy was performed on all patients and SNs and other nodes were evaluated.. Out of 101 patients, 21 had lymph-node metastases. The accuracy of SN identification was 97.0% (98/101) and the metastasis detection rate was 85.7% (18/21). With improvement of the manoeuvre in the latter 84 cases, the detection rate was elevated up to 100.0% (18/18), as was the accuracy (84/84).. The sentinel concept using lymphatic dye is applicable to gastric cancer, but the identification of SNs with lymphatic dye requires some practice. Furthermore, the issue of intraoperative metastasis detection remains to be resolved.

Topics: Adult; Aged; Aged, 80 and over; Coloring Agents; False Negative Reactions; Female; Frozen Sections; Gastrectomy; Humans; Incidence; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Rosaniline Dyes; Sentinel Lymph Node Biopsy; Stomach Neoplasms

Recently several noninvasive methods have been employed to detect circulating tumor cells (CTCs) in cancer patients. In this study, we have developed a highly sensitive, high-throughput colorimetric membrane-array method that was designed to detect a panel of mRNA markers including human telomerase reverse transcriptase (hTERT), cytrokeratin-19 (CK-19), carcinoembryonic antigen (CEA) and mucin 1 (MUC1) mRNA for the presence of CTCs in the peripheral blood of patients with gastric cancer (GC). Digoxigenin-labeled cDNA targets synthesized following total RNA isolation from peripheral blood samples of 64 GC patients and 80 healthy individuals were subjected to membrane-array hybridization. The results showed that membrane array could positively detect 5 cancer cells/ml of peripheral blood in GC cell-dilution experiments. The sensitivity, specificity and diagnostic accuracy for hTERT, CK-19, CEA and MUC1 mRNA ranged from 78.1% to 82.8%, 76.3% to 85% and 81.3% to 83.3%, respectively. Both CEA and MUC1 mRNA expression was correlated significantly with all malignant biological properties of GC, such as macroscopic type, depth of tumor invasion, lymph-node metastasis, TNM stage and coexisting distant metastasis (all p < 0.05). Using these 4 markers in combination, the sensitivity, specificity and diagnostic accuracy of membrane array were raised to 89.1%, 91.3% and 90.3%, respectively. The expression of all 4 mRNA markers was an independent predictor for postoperative recurrence/metastasis. GC patients with the expression of all the 4 mRNA markers showed a poorer survival rate than those without the expression of any 1 mRNA marker (p = 0.0223). These findings demonstrated that our membrane-array method could detect CTCs in the circulation of GC patients with considerably high sensitivity and specificity. The identification of CTCs in the peripheral blood may be useful in the auxiliary cancer diagnostics or postoperative surveillance of GC patients for recurrence/metastasis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Case-Control Studies; Colorimetry; DNA-Binding Proteins; Female; Gene Expression Regulation, Neoplastic; Humans; Keratins; Male; Middle Aged; Mucin-1; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Stomach Neoplasms; Survival Analysis; Telomerase

This study was designed to examine the relationship between the presence of occult neoplastic cells (ONCs) in lymph nodes (LNs) and survival in 238 patients with stage I/II LN-negative cancer of the breast, lung, or stomach. In addition, immunohistochemistry for TS and DPD was used to compare the 5-FU sensitivity of the primary tumor in ONC (+) patients. The 5-year relapse-free survival (RFS) rate of 215 ONC (-) patients and 23 ONC (+) patients was 95.2 and 82.6%, respectively (p=0.0107). The 5-year overall survival (OS) rate of the ONC (-) and (+) patients was 97.4 and 77.4%, respectively (p=0.0000). The 6 ONC (+) patients with recurrence showed high and low TS expression in 33.3% (2/6) and 66.7% (4/6), respectively, while high and low DPD expression was observed in 16.7% (1/6) and 83.3% (5/6), respectively. In the 17 ONC (+) patients without recurrence, the corresponding values were 64.7% (11/17), 35.3% (6/17), 29.4% (5/17), and 70.6% (12/17). Patients with a combination of high TS and low DPD expression accounted for 33.3% (2/6) of the ONC (+) patients with recurrence and 52.9% (9/17) of those without recurrence, showing no significant difference between the two groups. These results suggest that ONCs are associated with a lower survival rate and that ONC (+) patients are unlikely to respond to 5-FU+LV therapy.

Topics: Antimetabolites, Antineoplastic; Breast Neoplasms; Dihydrouracil Dehydrogenase (NADP); Female; Fluorouracil; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Stomach Neoplasms; Survival Analysis; Thymidylate Synthase

We evaluated the sensitivity and specificity of 10 monoclonal and two polyclonal antibodies for distinguishing epithelioid mesothelioma from adenocarcinoma (AdCA) using immunohistochemistry (IHC). The antibodies were directed against the mesothelial-associated antigens mesothelin, calretinin, cytokeratin 5, thrombomodulin, Wilms' tumor-1 (WT-1) gene product and HBME-1, and the nonmesothelial antigens Lewis-Y blood group (antibody BG8), MOC-31, BerEp4, CD15, and carcinoembryonic antigen (CEA) family. The 133 tumors evaluated included 65 malignant epithelioid mesotheliomas, 22 lung AdCAs, 27 ovarian serous carcinomas, 24 breast carcinomas, and five gastric carcinomas. Diagnoses were based on clinical, histologic, ultrastructural, and/or IHC findings. Calretinin had the best sensitivity for mesothelioma (95%), followed by HBME-1 (84%), WT-1 (78%), cytokeratin 5 (76%), mesothelin (75%), and vimentin and thrombomodulin (68%). Thrombomodulin had the best specificity for mesothelioma (92%), followed by cytokeratin 5 (89%), calretinin (87%) vimentin (84%), and HBME-1 (45%). When ovarian carcinomas were excluded from the analysis, the specificity of mesothelin and WT-1 for the diagnosis of mesothelioma increased to 90 and 81%, respectively. The sensitivity of the nonmesothelial antigens for AdCA was organ dependent, with BG8 performing best in the breast cancer group (96%), and BerEp4, BG8, MOC-31 performing best in the lung cancer group (100%). The specificity of the nonmesothelial antigens for AdCA was 98% for BG8 and CEA, 97% for CD15, 95% for BerEp4, and 87% for MOC-31. A novel statistical analysis technique employing logic regression analysis identified a three-antibody immunohistochemical panel including calretinin, BG8, and MOC-31, which provided over 96% sensitivity and specificity for distinguishing epithelioid mesothelioma from AdCA.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Breast Neoplasms; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Female; GPI-Linked Proteins; Humans; Immunohistochemistry; Keratin-5; Keratins; Lung Neoplasms; Membrane Glycoproteins; Mesothelin; Mesothelioma; Multivariate Analysis; Ovarian Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Stomach Neoplasms; Thrombomodulin; WT1 Proteins

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Keratin-20; Keratins; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Stomach Neoplasms; Telomerase

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

The Goseki system is a new gastric carcinoma classification system that classifies gastric carcinomas as grade I (intestinal type), grade II (mucinous type), grade III (mucin-poor, diffuse infiltrating type), and grade IV (signet ring cell type). The main advantage of the Goseki classification may be to separate these distinct entities into different groups. CK7 is not observed in normal gastric mucosa but can be detected in chronically inflamed gastric mucosa and coexists with incomplete intestinal metaplasia. CK20 can be observed in the superficial foveolar epithelium and mature goblet cells. The aim of this study was to examine the cytokeratin expression profiles in gastric carcinomas that are classified according to both the Goseki and Lauren systems. CK7, CK8, CK19, and CK20 were applied to the paraffin sections of 66 gastric carcinoma cases. The cytokeratin expression patterns were grouped as CK20+/CK7+, CK20+/CK7-, CK20-/CK7+, or CK20-/CK7-. The results were examined statistically. CK20 immunoreactivity was observed in 18%, 24%, and 31% of grade I, III, and IV cases, respectively. The CK20+/CK7- pattern was observed in 20% of the grade IV and 66.7% of the grade II carcinomas and was not observed in grade I or grade III tumors (P<0.0001). Goseki grade III and IV carcinomas originate from superficial gastric mucosa, but grade III carcinomas are poorly differentiated. Goseki grade II carcinomas have a specific immunophenotype other than intestinal-type gastric tumors. The Goseki classification seems to be superior in identifying poorly and well-differentiated forms of diffuse infiltrating carcinomas and mucinous carcinomas.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; Chi-Square Distribution; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Stomach Neoplasms

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

Staging of gastric carcinoma depends on exact lymph node status. However, very small lymph nodes can easily be missed during routine examination as they are obscured by the surrounding adipose tissue. The purpose of the present study was to verify the usefulness of a lymph node revealing solution (LNRS) in gastric cancer and compare its accuracy concerning the detection of lymph node metastases to immunostaining with cytokeratin antibodies. A total of 11 consecutive patients underwent standardized D2 gastrectomy for primary gastric adenocarcinoma. Non-fixed, the entire surgical specimen was searched for lymph nodes by palpation and visualization. The remaining tissue was immersed for 24 h in LNRS. The lymph nodes stood out as white chalky nodules on the background of yellow fat. All identified lymph nodes were resected and analyzed histologically. In 5 patients with pN0 status, immunostaining of the lymph nodes was performed using cytokeratin-specific antibodies. The conventional preparation of lymph nodes from the unfixed tissue yielded a total of 452 lymph nodes (mean 41.1 lymph nodes/patient; range, 26 to 56), and 201 of them had a pN0 status. After fixation using LNRS, 138 additional nodes could be detected (mean 12.5 lymph nodes/patient; range, 3 to 21), and 70 of them with a pN0 status. The detection rate of extremely small lymph nodes (<3 mm) increased by 27% compared to the conventional preparation technique (p=0.0017). After application of the LNRS lymph node analysis, it was not necessary to change the UICC node (N) stage in any cases. Additionally, we performed immunostaining in 5 specimens with pN0 status. In one patient, 10 micrometastases/disseminated tumour cells were detected. Thus, after immunohistochemical re-evaluation, one patient had to be upstaged pN(i+). By performing standardized LAD systematically and detailed lymph node preparation by the pathologist, a routine application of the LNRS method in gastric carcinoma is not recommended. Immunohistochemical techniques aid in identifying micrometastatic disease in lymph nodes missed in routine H&E staining in order to define the pN(i) status according to the TNM classification.

Topics: Acetic Acid; Adenocarcinoma; Ethanol; Ether; Formaldehyde; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Neoplasm Staging; Reproducibility of Results; Stomach Neoplasms

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

Endoscopic mucosal resection (EMR) is a minimally invasive, standard treatment for intramucosal (early) gastric cancers, but is not standard for submucosal gastric cancers based on existing criteria. We evaluated the possibility of extending EMR as a therapy for submucosal gastric cancers by analyzing nodal micrometastasis through immunohistochemical staining in patients with apparent node-negative submucosal gastric cancer, the patients for whom EMR might be appropriate. We used anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastasis that was not identified by routine pathological examination in 162 patients (total, 2048 lymph nodes) with apparent node-negative submucosal gastric cancer. The relationship between the incidence of nodal micrometastasis and clinicopathological factors was analyzed. Micrometastasis was detected in 45 of 2048 nodes (2.2%), representing 31 of 162 patients (19%). A significantly high incidence of nodal micrometastasis was found with submucosal cancers of large size (>2 cm), as well as with tumors that showed lymphatic or venous invasion and deeper submucosal invasion (p<0.0001). Nodal micrometastasis was also recognized in 2 cases of histologically well-differentiated tumors with focal submucosal invasion without venous or lymphatic invasion. Of the 162 patients, only 2 died of recurrent disease regardless of nodal involvement. Based on the present results, risk factors for nodal micrometastasis are tumor size, presence of lymphatic-vascular invasion, and depth of tumor, which are nearly the same as those established in previous pathological studies that used hematoxylin and eosin staining. We conclude that EMR is not recommended for patients with submucosal gastric cancer.

Topics: Aged; Aged, 80 and over; Female; Gastrectomy; Gastric Mucosa; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Stomach Neoplasms; Survival Rate

Patients with early gastric cancer may be treated by minimally invasive surgery. This study investigated the value of sentinel node (SN) navigation surgery, including detection of micrometastases, in patients with clinical (c) T1 and T2 gastric cancer.. The day before surgery (99m)Tc-radiolabelled tin colloid was injected submucosally near the tumour. After resecting the stomach, radioisotope uptake in all dissected lymph nodes was measured during and after surgery. Micrometastasis was detected immunohistochemically using an anticytokeratin antibody.. SNs were identified in 99 of 104 patients. The rate of identification of SNs in patients with cT1 and cT2 tumours, excluding three technical failures, was 99 and 95 per cent respectively. Lymph node metastases and/or micrometastases were found in 28 patients (15 cT1 and 13 cT2). In the 15 patients with cT1 tumours, at least one SN contained metastasis and/or micrometastasis. For cT1 tumours, the sensitivity and accuracy of detecting SNs were both 100 per cent. Six patients with cT2 tumours had false-negative results.. SN navigation surgery appears to be clinically useful only for cT1 tumours. Based on SN results, the extent of lymphadenectomy may be reduced in patients with early gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Stomach Neoplasms; Technetium Compounds; Tin Compounds

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

The current method for staging in gastric cancer is not sufficient as even after a complete primary tumor resection, patients with node-negative gastric cancer suffer from disease recurrence. In this study, the relation between disease recurrence and the presence of occult tumor cells (OTC) in lymph nodes from gastric cancer patients was evaluated. In a case-control design, lymph nodes from 40 cases (disease recurrence) and 41 controls (no disease recurrence and followed for at least five years) with gastric cancer were examined for the presence of OTC, that comprised micrometastases (MM; >0.2 mm and < or =2.0 mm) and isolated tumor cells (ITC; < or =0.2 mm). The original hematoxylin and eosin-stained sections of all lymph nodes from cases and controls were previously considered as tumor-negative by the local pathologist. Fresh hematoxylin and eosin-stained sections were screened by conventional microscopy. Histologic sections stained by immunohistochemistry with anticytokeratin antibodies CAM5.2 were screened by conventional and automated microscopy. Tumor cells were detected in lymph nodes from 40 of 81 (49%) patients. There was no significant difference in the presence of OTC, MM, or ITC between the case and control groups (P = 0.658, P = 0.691, P = 0.887, respectively). However, significantly more cases presented with 20% or more OTC-positive lymph nodes (P = 0.015). A multivariate logistic regression analysis showed that examination of less than five lymph nodes (odds ratio, 13.8; 95% confidence interval, 1.6-120.6, P = 0.018) was the only significant independent risk factor for disease recurrence, especially for locoregional disease recurrence (odds ratio, 20.4; 95% confidence interval, 2.2-190.8, P = 0.008). A similar analysis for distant disease recurrence showed a percentage of 20% or more OTC-positive lymph nodes to be the only significant independent risk factor (odds ratio, 15.6, 95% confidence interval, 1.6-151.4, P = 0.018). The sensitivity of immunohistochemistry evaluated by microscopy to identify cases with 20% or more OTC-positive lymph nodes increased from 8% for conventional microscopy to 22% for automated microscopy (McNemar's test, P = 0.063). The mere presence of OTC-positive lymph nodes in gastric cancer patients did not predict disease recurrence. However, the number of examined lymph nodes and the percentage of OTC-positive lymph nodes were independent risk factors for locoregional disease recurrence and distant disease recurrenc

Topics: Aged; Biomarkers; Case-Control Studies; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Sensitivity and Specificity; Stomach Neoplasms

The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.

Topics: Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Gastrointestinal Stromal Tumors; Hemangiosarcoma; Humans; Keratins; Mutation; Pelvic Neoplasms; Proto-Oncogene Proteins c-kit; Stomach Neoplasms

A null mutation in one copy of the Atp2a2 or ATP2A2 gene, encoding sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), leads to squamous cell tumors in mice and to Darier disease in humans, a skin disorder that also involves keratinocytes. Here, we examined the time course and genetic mechanisms of tumor development in the mutant animals. Atp2a2+/- mice overexpressed keratins associated with keratinocyte hyperactivation in normal forestomachs as early as 2 months of age. By the age of 5 to 7 months, 22% of mutants had developed papillomas of the forestomach, and 89% of mutants older than 14 months had developed squamous cell papillomas and/or carcinomas, with a preponderance of the latter. Tumors occurred in regions that had keratinized epithelium and were subjected to repeated mechanical irritation. The genetic mechanism of tumorigenesis did not involve loss of heterozygosity, as tumor cells analyzed by laser capture microdissection contained the wild-type Atp2a2 allele. Furthermore, immunoblot and immunohistochemical analysis showed that tumor keratinocytes expressed the SERCA2 protein. Mutations were not observed in the ras proto-oncogenes; however, expression of wild-type ras was up-regulated, with particularly high levels of K-ras. Loss of the p53 tumor suppressor gene occurred in a single massive tumor, whereas other tumors had increased levels of p53 protein but no mutations in the p53 gene. These findings show that SERCA2 haploinsufficiency predisposes mice to tumor development via a novel mode of cancer susceptibility involving a global change in the tumorigenic potential of keratinized epithelium in Atp2a2+/- mice.

Topics: Alleles; Animals; Calcium-Transporting ATPases; Carcinoma, Squamous Cell; Genes, p53; Genes, ras; Genetic Predisposition to Disease; Humans; Keratinocytes; Keratins; Loss of Heterozygosity; Male; Mice; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stomach Neoplasms; Tumor Suppressor Protein p53

Gastric mucosa associated lymphoid tissue (MALT) lymphoma is a low grade B cell lymphoma histologically characterised by neoplastic B cells surrounding follicles in a marginal zone pattern and selectively infiltrating epithelium to form characteristic lymphoepithelial lesions.. To identify solitary epithelial cells in gastric MALT lymphoma and investigate their nature.. Anonymised endoscopic biopsies from eight B cell gastric MALT lymphomas and 10 control biopsies from chronic atrophic gastritis were selected. The numbers of solitary cytokeratin positive epithelial cells were assessed both semiquantitatively and quantitatively in immunostained sections. Chromogranin A expression was studied in sections consecutive to those stained for cytokeratin.. Statistical analysis of the quantitative data confirmed that solitary epithelial cells were significantly more common in the lymphomas. The study of consecutive sections showed that the single cells express chromogranin A.. The presence of solitary, cytokeratin positive epithelial cells within the neoplastic infiltrate is a characteristic feature of gastric B cell lymphoma. These solitary epithelial cells are of neuroendocrine origin.

Topics: Chromogranin A; Chromogranins; Epithelial Cells; Gastritis, Atrophic; Humans; Keratins; Lymphoma, B-Cell, Marginal Zone; Stomach Neoplasms

To determine the prognostic significance of isolated tumor cells (ITCs) and lymph node micrometastases in gastric cancer.. Hematoxylin and eosin-stained slides of lymph node dissections of 632 consecutive gastric cancers were reviewed. Cytokeratin immunostaining was performed in 280 node-negative cases and 5 cases indefinite for lymph node metastases. Lymph node metastases were divided into ITCs, micrometastases, or macrometastases, according to the sizes of tumor deposits in largest dimension. ITCs were further classified into four groups according to metastasis pattern.. Lymph node metastases were identified by immunostaining in 58 of 280 node-negative cases (20.7%) and were not significantly associated with patient survival (P = 0.3460). After cytokeratin immunostaining, 196 cases were classified as pN1, which consisted of 20 cases with micrometastases detected by immunostaining (pN1mi(i+)), 34 cases with only micrometastases (pN1mi), and 142 cases with pN1 with one or more macrometastases (pN1). Cases with pN1mi and pN1mi(i+) had a significantly better prognosis than the cases with pN1 (P = 0.0037). ITCs were found in 38 of these 58 cases, and could be divided into four groups: 12 cases with only a single cell pattern, 7 cases with multiple individual cells, 5 cases with single small cluster, and 14 cases with multiple small clusters. Among these four groups, cases with ITCs of multiple individual cell pattern showed the worst survival (median survival: 28 mo, P<0.0001).. Both size and pattern of lymph node metastases can give prognostic information on the survival of gastric cancer patients.

Topics: Humans; Keratins; Korea; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate

To explore the biological behavior of gastric carcinoma micrometastasis (MM) with a marker of cytokeratin 18 (CK18) and to evaluate the clinical stage of gastric carcinoma and its prognosis.. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of CK18 mRNA in 298 lymph nodes from 35 patients with gastric carcinoma and 20 lymph nodes from 10 patients with chronic peptic ulcer and gastric perforation diagnosed by pathological examination and surgery. CK18 mRNA expression of peripheral blood from 54 patients with gastric carcinoma and 10 healthy people were also examined.. Expression of CK18 mRNA was not found in 10 patients with benign pathological changes. CK18 mRNA expression in gastric carcinoma tissues was strongly positive. In gastric carcinoma patients, pathological examination revealed that 99 of 298 (33.2%) lymph nodes were positive, while RT-PCR showed that 133 of 298 (44.6%) lymph nodes had expression of CK18 mRNA. The difference was significant (P<0.05). Among the 199 negative lymph nodes identified by pathological examinations, 34 (17.1%) displayed positive expression of CK18 mRNA by RT-PCR. The positive expression of CK18 mRNA was associated with lymph node micrometastasis (LMM) of gastric carcinoma. CK18 mRNA was negatively expressed in all 10 healthy cases and positively expressed in 38.9% of 54 blood specimens from gastric carcinoma patients. The positive rate was not correlated with tumor invasion of gastric carcinoma, but was significantly associated with TNM stage, lymph node metastasis (P=0.0290, P<0.05) and tumor differentiation (P=0.2956, P<0.05).. RT-PCR with CK18 mRNA as a molecular marker is highly sensitive and specific in detecting LMM of gastric carcinoma. It can benefit the diagnosis of MM and guide studies on biological behavior, clinical phase, and therapy as well as relapse monitoring.

Topics: Adult; Aged; Biomarkers, Tumor; Female; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Prognosis; Stomach Neoplasms

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

Cytokeratin (CK) is observed mainly in epithelial cells, and the diverse expression pattern of CK subtypes may be helpful in discriminating between primary and metastatic carcinomas in various organs, including the stomach. To clarify the CK expression profiles in gastric carcinomas, 329 consecutive specimens were immunohistochemically evaluated in terms of their CK subtypes using the tissue array method. The overall positive rates were 84.7% for CK4, 3.2% for CK5, 28.7% for CK6, 71.1% for CK7, 96.6% for CK8, 0% for CK10, 81.6% for CK13, 0.3% for CK14, 4.1% for CK16, 0% for CK17, 99.4% for CK18, 89.7% for CK19, and 30.0% for CK20. Well-differentiated or moderately differentiated carcinomas were related to several CKs, and mucinous carcinoma was associated with CK20 expression. Interestingly, CK7 and CK20 expression was associated with the mucin phenotype of gastric carcinoma, but this association had no diagnostic value. Epstein-Barr virus (EBV)-associated gastric carcinomas showed a tendency toward negative expression of CK7. CK6 expression was related to microsatellite instability (MSI), early pTNM stage, and better clinical outcome. In conclusion, CK expression profiles in consecutive gastric carcinomas demonstrate heterogeneity, and no single CK has diagnostic value by itself. CK expression is associated with various clinicopathologic parameters, mucin phenotype, EBV positivity, MSI status, and patient survival.

Topics: Biomarkers, Tumor; Female; Gene Expression; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Prognosis; Protein Isoforms; Stomach Neoplasms

Paraaortic lymph nodes dissection in advanced gastric carcinoma is controversial. Investigation of micrometastasis in these critical lymph nodes is important in the evaluation of prophylactic lymphadenectomy.. A total of 2 339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically using cytokeratin antibody.. Paraaortic lymph node metastasis was found in 95 of 390 nodes of 14 patients by routine histological examination. Micrometastasis in the paraaortic lymph nodes was immunohistochemically detected in 45 of 295 negative nodes from 15 of 33 patients. The 5-year-survival rate in patients with paraaortic lymph node metastasis was 56.0% in the node negative group, 25.2% in the cytokeratin positive group and 9.0% in the hematoxilin and eosin positive group.. We have demonstrated a high rate of micrometastasis in the paraaortic lymph nodes of patients with advanced gastric carcinoma and have confirmed that prophylactic lymphadenectomy of these nodes is effective for such patients.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate

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

Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.

Topics: Animals; Apoptosis; Bone Marrow Cells; Bone Marrow Transplantation; Carcinoma in Situ; Cell Differentiation; Cell Fusion; Disease Progression; Female; Gastric Mucosa; Gastritis; Helicobacter felis; Helicobacter Infections; Keratins; Male; Mesenchymal Stem Cells; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mucins; Muscle Proteins; Parietal Cells, Gastric; Peptides; Phenotype; Stem Cells; Stomach Neoplasms; Trefoil Factor-2

To evaluate the effect of a novel blockade technique for gastric cancer on blood-borne metastasis of gastric cancer cells to portal vein.. Twenty-three cases of gastric cancer were divided into routine operation group (8 cases intraoperatively without blockade technique) and blockade group (15 cases with blockade technique). Blood samples from portal vein pre- and intraoperatively, as well as gastroepiploic vein limited within the blockade area were obtained to detect CK19 mRNA expression by using RT-PCR technique.. Before the dissection of gastric lesion, the overall positive rate of CK19 mRNA expression in portal vein blood is 34.7% (9/23), including 37.5% (3/8) in routine operation group and 33.3% (5/15) in blockade group. While the course of tumor resection, those positive rates were 87.5% (7/8) in routine operation group and 6.7% (1/15) in blockade group respectively (P < 0.05). CK19 mRNA expression in the right gastroepiploic venous blood limited within the blocking area was all positive in 15 cases of blockade group.. This blockade technique can be used effectively to block the intraoperative spread of gastric cancer cells, thus prevent blood-borne metastasis due to operative manipulation.

Topics: Aged; Biomarkers, Tumor; Female; Gastrectomy; Humans; Keratins; Ligation; Male; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Vascular Surgical Procedures

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

The existence of occult metastasis in peripheral blood has been reported in various tumors. However, in gastric cancer (GC), this metastasis has not been well analyzed. In the present study, to identify circulating cancer cells in patients with GC, peripheral blood samples from GC patients were investigated. Total RNA was extracted from 1.5 ml peripheral blood from 55 patients with GC, from 34 non-cancer patients, and from 10 healthy volunteers. Carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and 20 (CK20) messenger RNA (mRNA) were used as probes to detect GC cells in the blood samples using real-time reverse transcriptase polymerase chain reaction (RT-PCR). CEA and CK19 mRNA expression were not detected in the 40 healthy volunteers and non-cancer patients, while 2 of the 40 showed CK20 mRNA expression. In 55 patients with GC, CK19 mRNA was not detected and CEA mRNA was detected in only one case (1.8%) with stage IV. While CK20 mRNA expression was observed in 15 cases (27.3%) and even in stage I, 8 of 24 (33.3%) showed CK20 mRNA expression. Thus, the specificity of CK20 marker may be low. Even though the sensitivity of CEA marker is low, CEA may be a more reliable marker than cytokeratins for detection of cancer cells in GC patient's peripheral blood.

Topics: Adult; Aged; Carcinoembryonic Antigen; Female; Humans; In Vitro Techniques; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Tumor Cells, Cultured

Micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients after surgery. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of gastric cancer patients.. Bone marrow and peripheral blood samples were obtained from 53 gastric 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 and erbB-2/HER2 was examined in the primary tumors.. Cytokeratin-positive cancer cells were observed in the bone marrow of 16 (30%) of 53 patients. Among them, two patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with the depth of invasion and lymph node metastasis but was not associated with peritoneal dissemination. Detection of bone marrow micrometastasis was not correlated with vascular endothelial growth factor or HER2 expression in the primary tumors. Four patients with micrometastasis had recurrence in the liver or lungs, but this did not occur in patients without micrometastasis.. Detection of cancer cells in the bone marrow might be an indicator of postoperative hematogenous metastasis in gastric cancer patients.

Topics: Adult; Aged; Bone Marrow Neoplasms; Chi-Square Distribution; Endothelial Growth Factors; Female; Humans; Immunoenzyme Techniques; Immunomagnetic Separation; Intercellular Signaling Peptides and Proteins; Keratins; Lymphatic Metastasis; Lymphokines; Male; Middle Aged; Neoplasm Invasiveness; Neoplastic Cells, Circulating; Prognosis; Receptor, ErbB-2; Stomach Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

A frequent genetic alteration found in premalignant stages of pancreatic adenocarcinoma is K-ras oncogene point mutation. The mechanistic basis for the inability of K-ras mutation to transform pancreatic ductal cells is unclear, although cooperating events with p16 inactivation, p53 mutation, and SMAD 4 mutation are recognized to be necessary. We have generated a novel mouse model in which the cytokeratin 19 promoter, specifically active in pancreatic ductal cells but not other cell types of the pancreas, is fused to mutant K-ras. This is of direct relevance to human pancreatic cancer because premalignant lesions are found specifically in ductal cells. There is dramatic periductal lymphocytic infiltration in the pancreata of transgenic mice, predominantly CD4+ T lymphocytes, which may act as an adaptive immune response to activated ras-mediated signaling. In addition, gene array analysis reveals an induction of N-cadherin in transgenic mice pancreatic ductal cells, the significance of which relates to promotion of cell adhesion and deterrence of cell migration. Apart from these important biological considerations, there is parallel activity of the cytokeratin 19 promoter in the stem cell region of the gastric epithelium, namely in mucous neck cells. Activated K-ras in this context causes mucous neck cell hyperplasia, a precursor to gastric adenocarcinoma. There is concomitant parietal cell decrease, which is a key step toward gastric adenocarcinoma. Taken together, we have defined how mutant K-ras signaling modulates important molecular events in the initiating events of pancreatic and gastric carcinogenesis.

Topics: Adenocarcinoma; Animals; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Gastric Mucosa; Genes, ras; Humans; Hyperplasia; Keratins; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Transgenic; Mutation; Pancreatic Neoplasms; Precancerous Conditions; Promoter Regions, Genetic; Stomach Neoplasms; Transfection; Tumor Cells, Cultured

In patients undergoing surgery for gastric cancer, as the resection area is difficult to define preoperatively, we define the resection area by intraoperative rapid pathological assessment of the resected margin. In some patients, however, the result of postoperative assessment of a permanent section differs from the result obtained intraoperatively. In this study we explored methods of improving the accuracy of intraoperative pathological assessment. Of the patients who underwent surgery for gastric cancer at Takarazuka Municipal Hospital, between April 2000 and July 2001, intraoperative pathological assessment of the resection margin was performed in 34 because it could not be accurately defined preoperatively. The intraoperative assessment consisted of touch smear cytological examination and hematoxylin and eosin (HE) and cytokeratin (CK) histological examination. The time required to perform cytological examination and HE and CK immunohistochemistry by this modified method, which uses an ENVISION Kit/HRP, was approximately 20 minutes for each procedure. Touch smear cytological examination gave false positive results in 3 of 34 patients (8.8%). Of the 14 patients preoperatively diagnosed with signet-ring cell carcinoma, intraoperative HE histological analysis yielded a false negative result in one (7.1%). The results of CK histological assessment of these patients were all consistent with those of postoperative examination of permanent sections. Of the 20 patients preoperatively diagnosed with non-signet-ring cell carcinoma, HE analysis yielded a false negative result in one (5%). The results of CK histological assessment of these patients were all consistent with those of postoperative examination of permanent sections. Our modified CK staining method with the ENVISION Kit/HRP allows intraoperative pathological assessment to be performed accurately and rapidly. This method is more useful than HE immunohistochemistry for the assessment of resected gastric margins.

Topics: Carcinoma, Signet Ring Cell; Humans; Immunohistochemistry; Intraoperative Period; Keratins; Reagent Kits, Diagnostic; Stomach Neoplasms

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

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

Micrometastasis in regional lymph nodes has been observed immunohistochemically, but the biological and clinical roles of minute nodal invasion of carcinoma in gastric cancer remain unclear. We used the anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastatic lesions that could not be identified by routine pathological examination. A total of 4203 lymph nodes were examined in 180 gastric cancer patients. Lymph node metastasis was found in 36 of the 180 patients by routine pathological evaluation. Immunohistochemically micrometastasis was detected in the lymph nodes of 19 node-negative patients. Micrometastasis was not detected in any of the mucosal gastric cancer patients who underwent lymph node dissection. Gastric cancer patients with more than six metastatic lymph nodes all had nodal micrometastasis. Patients with micrometastasis had a significantly poorer survival rate than those without micrometastasis (P < 0.05). Based on the present results the presence of lymph node micrometastasis may provide a more accurate indication for surgical outcome in gastric cancer patients at the same clinical stage.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Gastrectomy; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms; Survival Rate

A case of gastric carcinosarcoma with a rare histology is reported. Grossly, a huge ulcerative tumor (Borrmann type 3 tumor, measuring 10 x 6 cm) was observed on the lesser curvature side of the stomach. Microscopically, the tumor consisted of carcinoma and sarcoma components. The main tumor component consisted of an endocrine cell carcinoma exhibiting positive reactions for cytokeratins, chromogranin A, synaptophysin, and CD56. The sarcoma component occupied less than 10% of the entire tumor area and consisted of spindle cells, some of which showed a rhabdomyosarcoma differentiation. Some of the spindle cells also showed an atypical cartilage or osseous differentiation. This sarcoma component exhibited positive staining not only for vimentin and desmin, but also for cytokeratins. Transitions between these two components were occasionally observed. These findings suggest that the sarcoma component in our case most likely originates from the endocrine cell carcinoma component.

Topics: Carcinosarcoma; Desmin; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Staining and Labeling; Stomach Neoplasms; Vimentin

The sentinel node (SN) is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of the remaining nodes in the basin. We succeeded in detecting SNs of clinically early gastric cancers by intraoperative injection of a blue dye around the tumour. In the study presented here, multiple-marker reverse transcription-polymerase chain reaction (RT-PCR) was used to detect micrometastases in SNs and results were compared with those obtained with conventional histology. Expressions of cytokeratin-18 (CK-18), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTRT) and MUC-1 in SNs were determined by RT-PCR and Southern blot assay. Of the 213 SNs obtained from 35 cases of gastric cancer, eight nodes (3.8%) from five patients contained metastases that could be identified by conventional histology. However, CK-18 mRNA was expressed in 15 (7.0%), CEA in 12 (5.6%), hTRT in 10 (4.7%), and MUC-1 in 12 (5.6%) nodes, with at least one mRNA marker expressed in 25 nodes (11.7%) obtained from six patients. In the five patients with nodal metastases identified by conventional histology, two had metastases in both SNs and non-SNs. And, in the 30 patients without nodal metastases identified by conventional histology, one patient with micrometastases in the SNs identified by RT - PCR and Southern blot assay also had metastases in non-SNs as identified by serial sectioning and immunostaining of CK-18. All additional metastases were detected in non-SNs located in the same lymphatic basin as the previously detected SNs. This suggests that lymph node dissection of early-stage gastric cancer in the lymphatic basin may be mandatory even for patients without histologically detectable metastases in SNs.

Topics: Adenocarcinoma; Adenocarcinoma, Papillary; Blotting, Southern; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Case-Control Studies; DNA Primers; DNA-Binding Proteins; Gastrectomy; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Mucin-1; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Stomach Neoplasms; Telomerase

To investigate the role of Epstein-Barr virus (EBV) in epithelial tumors, we compared the expression pattern of cellular genes in the EBV-infected gastric carcinoma cell line, NU-GC-3, and its uninfected control. Subtractive suppression hybridization (SSH) was combined with high-density DNA array screening to identify differentially expressed genes. We have discovered that EBV infection upregulated a truncated variant of human basic hair keratin 1 (hHb1-DeltaN), a gene that had previously been identified in metastatic breast carcinoma. We verified the differential expression of hHb1-DeltaN in 3 independent EBV-positive and -negative NU-GC-3 clones by Northern blotting. We further verified the EBV-dependent upregulation of hHb1-DeltaN in 3 other carcinoma cell lines (AGS, TWO3 and DLD1) by RT-PCR. Inhibition of CpG methylation by 5-Aza-CdR induced hHb1-DeltaN mRNA expression in the EBV-negative clones but did not alter the expression in the EBV-positive clones. The expression of hHb1-DeltaN protein was detectable by immunofluorescence and Western blotting in EBV-positive but not in EBV-negative NU-GC-3 clones after proteasome inhibitor (MG132) treatment. hHb1-DeltaN protein formed fibrous structures in the cytoplasm and accumulated in distinct nuclear bodies in the euchromatic areas of the cell nucleus. We suggest that the unstable hHb1-DeltaN protein may inhibit some of the functions of the keratin cytoskeleton and/or interfere with transcription regulation. It also may establish a link between EBV and the low differentiated or anaplastic status of the carcinomas that carry the virus.

Topics: Azacitidine; Blotting, Northern; Blotting, Western; CpG Islands; Cysteine Proteinase Inhibitors; Decitabine; DNA Methylation; DNA Modification Methylases; Enzyme Inhibitors; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Herpesvirus 4, Human; Humans; Keratins; Leupeptins; Oligonucleotide Array Sequence Analysis; Protein Biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Tumor Cells, Cultured; Up-Regulation

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

Micrometastases consisting of one to a few cells in lymph nodes resected during gastrectomy are difficult to identify using conventional hematoxylin and eosin (H&E) stains. It has been shown that immunostaining for cytokeratins is effective in detecting lymph node micrometastasis in a variety of human tumors, but only a few previous reports demonstrated its use in the treatment of patients with early and advanced gastric carcinoma, and those reports had conflicting results.. In this study, 3625 regional lymph nodes that were dissected in gastrectomy specimens from 153 patients with early-stage gastric carcinoma (46 patients) and advanced gastric carcinoma (107 patients) were immunostained with the anticytokeratin cocktail AE1/3 for micrometastasis (median, 23 lymph nodes; range, 8-66 lymph nodes). Micrometastasis (MM) was defined as a single tumor cell or clusters of tumor cells that were missed on conventional examination with H&E stains but were detected by immunostaining with broad-spectrum anticytokeratin antibodies.. Lymph node metastasis (LNM) was detected in 609 lymph nodes (17%) by H&E staining. MM was identified in another 191 of the remaining lymph nodes (6.3%) from 75 patients. Twenty-eight of those patients were up-staged. There was a significant correlation between MM and depth of tumor invasion (P < 0.01). Patients with MM had a decreased 5-year survival rate (49%) compared with patients without MM (76%) for both early and advanced gastric carcinoma. The effect of MM on survival was most pronounced for patients in the Stage I and LNM negative group.. Immunohistochemical examination using broad-spectrum anticytokeratin antibodies increased the detection rate of LNM and had a significant impact on staging and survival in patients with gastric carcinoma.

Topics: Adenocarcinoma; Follow-Up Studies; Humans; Immunoenzyme Techniques; Intestinal Neoplasms; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Rate

To investigate the expression of cancer related genes in gastric carcinoma (GC) through the use of Atlas Human Cancer Array membranes with 588 well-characterized human genes related to cancer and tumor biology.. Hybridization of cDNA blotting membrane was performed with (32)P-labeled cDNA probes synthesized from RNA isolated from gastric carcinoma and adjacent noncancerous gastric epithelial tissue. AtlasImage, which is a software specific to array, was used to analyze the result.. The differentially expression cell cycle/growth regulator in GC showed a stronger tendency toward cell proliferation with 2.7-fold up-regulation of CK1. The promoter genes of apoptosis were down-regulated, including caspase-8 precursor, caspase-9 and caspase-10. Among the oncogene/tumor suppressor genes, ABL2 was down-regulated. In addition, some genes were up-regulated, including matrix metalloproteinse 2(MMP-2), MMP-16(MT3-MMP), SKY, CD9 and semaphorin V. A number of genes were down-regulated, including neuroendocrine-dlg (NE-dlg), retinoic acid receptor gamma and tumor suppressor DCC colorectal. In general, The expression of the cancer progression genes were up-regulated, while the expression of anti-cancer progression genes were down-regulated.. Investigation of these genes should help to disclose the molecular mechanism of the onset, progression and prognosis of GC. Several genes are reported herein to be altered in GC for the first time. The quick and high-throughout method of profiling gene expression by cDNA array provides us with an overview of key factors that may involved in GC, and may aid the study of GC carcinogenesis and provide molecular targets for diagnosis and therapy. The precise relationship between the altered genes and gastric carcinogenesis is a matter for further investigation.

Topics: Antigens, CD; Caspases; Gastric Mucosa; Gene Expression Profiling; Genes, Tumor Suppressor; Humans; Keratins; Matrix Metalloproteinases; Membrane Glycoproteins; Oligonucleotide Array Sequence Analysis; Receptors, Retinoic Acid; Stomach Neoplasms; Tetraspanin 29

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

Bone marrow is a prognostically relevant indicator organ for micrometastasis. In the present study, real time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect disseminated gastric cancer cells in bone marrow. We compared CEA, CK18 and CK20 expression using four gastric cancer cell lines and three normal tissue cell lines in order to select the most appropriate marker for detection of disseminated gastric cancer cell in bone marrow. CK20 proved to be the most promising marker since the expression level of normal cell lines was extremely low and about 50--100-fold differences were found between gastric carcinoma cell lines and normal tissue cell lines. We also screened bone-marrow RNA of 47 patients with gastric cancers, using this system. Among the three markers we tested, with only about CK20 could we find that 27 of 47 patients were positive. Though long-term clinical follow up studies are needed to evaluate the clinical significance of this method, real time quantitative RT-PCR is sensitive and quantitative for detection of micrometastasis in bone marrow.

Topics: Adenocarcinoma; Biomarkers, Tumor; Bone Marrow Neoplasms; DNA Primers; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; Stomach Neoplasms

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.

Topics: Adenocarcinoma; Colorectal Neoplasms; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms; Tissue Embedding

We report a case of early adenocarcinoma arising in foci of intestinal metaplasia (IM) at a normal-appearing gastroesophageal junction (GEJ). The tumor infiltrated the submucosa without nodal involvement (T1N0). Non-neoplastic mucosa adjacent to neoplasia had foci of incomplete IM with a band-like CK20 positivity of the surface epithelium and a diffuse CK7 staining of both superficial and deep glands. There were histological features of reflux esophagitis as well as chronic non-atrophic, Helicobacter pylori-related pangastritis, without IM, at the extensively assessed gastric mucosa. In this case, the CK7/20 pattern of IM adjacent to neoplasia, the demonstration of reflux esophagitis, and the absence of IM in the stomach favor the theory that the pathogenesis of IM and associated adenocarcinoma of the GEJ is related to gastroesophageal reflux rather than H. pylori infection.

Topics: Adenocarcinoma; Aged; Cardia; Chronic Disease; Esophagogastric Junction; Gastrectomy; Gastric Mucosa; Gastritis; Humans; Immunohistochemistry; Keratins; Male; Metaplasia; Stomach Neoplasms

Intermediate filaments are known as cytoskeletal elements. Recently, additional vimentin expression has been reported in some carcinomas; however, the function of such expression remains unclear. We studied the intracellular distribution of low-molecular weight cytokeratin and vimentin by immunohistochemistry in 17 vimentin-positive gastric carcinomas using confocal laser scanning microscopy. All materials were formalin-fixed and paraffin-embedded. Low-molecular weight cytokeratin expression showed a membranous pattern with a prominent deposition just below the cytoplasmic membrane in both tubular and solid components of the carcinomas. This unique membranous deposition was frequently absent in diffuse components. On the other hand, vimentin expression showed a fibrillary pattern in all components and also showed a unique basal distribution in the tubular components. We also recognized an aggregate pattern of the intermediate filament expression in diffuse components. We conclude that the significance of vimentin expression in carcinoma cells cannot be explained as a simple substitution for low-molecular weight cytokeratin because the distribution of vimentin and low-molecular weight cytokeratin is different.

Topics: Adenocarcinoma; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Microscopy, Confocal; Stomach Neoplasms; Vimentin

The independent prognostic significance of isolated tumour cells in bone marrow is still a matter of debate. This study evaluated the possible association of bone marrow micrometastases with tumour progression and prognosis in patients affected by gastric cancer. Bone marrow aspirates from both iliac crests were obtained from 114 consecutive patients operated on for gastric cancer. The specimens were stained with monoclonal antibody CAM 5.2 which reacts predominantly with cytokeratin filaments 8 and 19. Among 114 cases analysed, 33 cases (29%) had cytokeratine-positive cells in the bone marrow. There was no significant relationship between the presence of bone marrow micrometastases and site, depth of tumour invasion, lymph node metastases, presence of metastases. Patients with cytokeratine-positive cells had a trend towards a diffuse type histology (P=0.06). Among the 88 curatively resected patients, median survivals were 40 months and 36 months for cytokeratine-negative and cytokeratine-positive subsets respectively (P=0.9). Recurrence of the disease was observed in 39 cases (44.3%); 11 of 24 (45.8%) in the cytokeratine-positive subset and 28 of 64 (43.7%) in the cytokeratine-negative subset. In conclusion in our experience the presence of cytokeratine-positive cells in the bone marrow of curatively resected gastric cancer patients did not affect outcome and its independent prognostic significance remains to be proven before its official acceptance in the TNM classification.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Bone Marrow Cells; Bone Marrow Neoplasms; Disease Progression; Female; Follow-Up Studies; Humans; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Predictive Value of Tests; Stomach Neoplasms; Survival Analysis; Treatment Outcome

To study the invasion-related molecule urokinase-type plasminogen activator receptor (u-PAR) expressed by disseminated tumor cells as a biologic predictor of poor survival in a large prospective series of patients with gastric cancer.. In 156 gastric cancer patients (prospective series), disseminated tumor cells in the bone marrow and the u-PAR expressed by these tumor cells were determined by cytokeratin (CK) 18 immunocytochemistry and u-PAR/CK18 double immunocytochemistry.. In contrast to the mere detection of disseminated tumor cells at primary surgery, the additional evidence of u-PAR on these cells correlated significantly with pathologic T stage (P =.0474) and the expression of u-PAR (P =.0093) and plasminogen-activator inhibitor 1 (P =.0145) in the primary tumor (immunohistochemistry, chi(2)). Kaplan-Meier analysis revealed no association with prognosis for the mere detection of disseminated tumor cells. In contrast, a significant association was seen between detection of u-PAR on these cells and shorter disease-free (P <.0001) and overall survival (P <.0001). Multivariate analysis revealed that u-PAR on disseminated tumor cells at the time of primary surgery is an independent prognostic factor for disease-free (95% confidence interval [CI], 1.72 to 3.21; P =.024) and overall survival (P =.0049; relative risk, 2.89; 95% CI, 1.92 to 4.30).. This is the first large study to show that u-PAR, detected on disseminated tumor cells in the bone marrow, is an independent prognostic parameter in gastric cancer, in contrast to the mere detection of minimal residual disease (MRD). u-PAR may be a promising marker to define a critical subpopulation of disseminated tumor cells and a target to eliminate MRD. Molecular phenotyping of MRD is critical for defining its individual clinical relevance.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Bone Marrow Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Neoplasm, Residual; Plasminogen Inactivators; Prognosis; Prospective Studies; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Stomach Neoplasms; Survival Analysis; Urokinase-Type Plasminogen Activator

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

The clinicopathologic significance of micrometastasis (MM) and tumor cell microinvolvement (TCM) in regional lymph nodes as identified by immunohistochemical staining for cytokeratin expression was evaluated in patients with node-negative gastric cancer.. MM was defined as tumor cells with stromal reaction, and TCM was defined as individual tumor cells without stromal reaction. We investigated 1761 lymph nodes obtained from 67 gastric cancer patients whose diagnosis showed no lymph node metastasis by routine histological examination. The depth of tumor invasion was T1 (submucosa) in 33 patients and T2 (muscularis propria and subserosa) in 34 patients. The lymph nodes were examined immunohistochemically for the presence of tumor cells using anti-cytokeratin AE1/AE3 monoclonal antibody. Both the biopsy tumor specimens obtained prior to surgery and the resected primary tumors were immunostained with E-cadherin (E-cad) monoclonal antibody.. Thirty (1.5%) of the 1761 lymph nodes showed MM and/or TCM. MM with or without TCM was found in 10 patients, and TCM alone was found in 4 patients; 6 (18.2%) of the 33 patients with T1 tumor and 8 (23.5%) of the 34 patients with T2 tumor had occult lymph node metastasis. The 5-year survival rate was worse among those with MM with or without TCM, than among those without MM. Nearly all of the patients with MM and/or TCM had reduced or negative E-cad expression in the primary tumor.. We demonstrated that the incidence of MM and/or TCM in the lymph nodes of patients with gastric cancer is quite high, and that such metastasis is associated with the prognosis of patients with pN0. Examination of E-cad expression in biopsy tumor specimens may be useful for predicting MM and/or TCM.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cadherins; Female; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Stomach Neoplasms

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

To clarify whether intraglandular necrotic debris (IND) is a diagnostic clue to noninvasive high-grade neoplasia or invasive neoplasia of the stomach, we reviewed 135 gastric biopsy specimens and 55 surgical materials. Intraglandular necrotic debris is defined as an eosinophilic material with necrotic epithelial fragments within the lumen of a dilated atypical gland. Using the Vienna classification, the incidence of IND in category 4 (noninvasive high-grade neoplasia) and category 5 (invasive neoplasia) was significantly higher than that of category 1 (negative for neoplasia/dysplasia), category 2 (indefinite for neoplasia/dysplasia), and category 3 (noninvasive low-grade neoplasia). The incidence of IND was much higher in category 5 than in category 4 in biopsy specimens. In addition, cases with IND in category 4 in biopsy specimens turned out to be either carcinoma in situ or invasive carcinoma in the surgical specimens. According to the histologic classification of surgically removed invasive carcinoma, moderately differentiated adenocarcinoma showed the highest incidence of IND. Intraglandular necrotic debris was not found in either signet-ring cell carcinoma or mucinous adenocarcinoma. Our results indicate that IND in biopsy specimens is a diagnostic clue to noninvasive high-grade neoplasia or invasive carcinoma, and the origin of IND may be associated with necrotic atypical epithelium.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Biopsy; Female; Gastric Mucosa; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Necrosis; Neoplasm Invasiveness; Stomach Neoplasms

Limited operations for early gastric cancer (EGC) have been recommended based on data from lymph node (LN) metastasis detected by hematoxylin and eosin (HE) staining. Recently, the clinical importance of micro-LN metastasis has been reported. In this study, the indication of limited operations for EGC was re-evaluated based on the data from micro-LN metastasis detected by cytokeratin (CK) immunostaining. Also, the correlation between micro-LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in primary tumors was evaluated.. A total of 5,949 LNs from 160 patients with EGC were stained by anti-CK monoclonal antibody (CAM 5.2). Also, the 160 primary EGCs were stained by CD.. The incidence of LN metastasis increased from 7.5% (12/160) by HE-staining to 27.5% (44 of 160) by CK immunostaining. The incidence of micro-LN metastasis increased according to the depth of tumor invasion (mucosal cancer: 19% and submucosal cancer: 36.8%) and the size of tumors (< or = 1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and > 2.1 cm: 31.7%). The CK-staining patterns were classified into the three subgroups (CK-negative, n = 116; single cell type, n = 27; and clustered type, n = 17). The occurrence of cancer recurrence was significantly higher in clustered type (17.6%) than in single cell type (3.7%) and in CK-negative (0%, P < 0.0001). The mean percentage of CD-positive cancer cells of primary tumors in clustered type (17.2%) was significantly higher than in single cell type (12.3%) and in CK-negative (7.5%, P = 0.0036).. The acidic protease CD may play an important role of cancer metastasis in EGC. The limited operation without lymphadenectomy should be indicated for EGC with CD-negative.

Topics: Cathepsin D; Gastrectomy; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness; Stomach Neoplasms; Survival Analysis

Topics: Adenocarcinoma; Biopsy; Breast Neoplasms; CA-19-9 Antigen; Female; Gastric Mucosa; Gastroscopy; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Stomach Neoplasms

Lymph node status is a major determinant of disease recurrence after patients undergo curative resection for gastric carcinoma. A proportion of patients without lymph node metastasis develop systemic recurrences. Recent studies in a range of solid tumors have found a high incidence of micrometastases in the regional lymph nodes of patients with apparently negative lymph nodes. In patients with breast and colorectal carcinoma, the presence of micrometastases has been associated with a poorer prognosis. In patients with gastric carcinoma, the significance of micrometastases in lymph nodes remains controversial. Most published reports on this subject suffer from the problems of small sample size and selection bias.. One hundred seven patients with pathologic T2N0M0 (tumor invades muscularis propria or subserosa [T2], no regional lymph node metastasis [N0], and no distant metastasis [M0]; pT2N0M0) gastric carcinoma who underwent gastric resection between 1984 and 1990 at the National Cancer Center Hospital were studied. Two consecutive sections were newly prepared from each lymph node for hematoxylin and eosin staining and immunohistochemical staining (IHC) with antibody against cytokeratin. Associations between clinicopathologic factors and the presence of micrometastases as well as micrometastases and survival were sought.. Micrometastases were identified in 38 of 107 patients (35.5%) and in 87 of 4484 lymph nodes (1.94%) by IHC. The incidence of micrometastases was significantly higher in patients with infiltrative tumors than in patients with expansive, growing tumors (P = 0.02). Other clinicopathologic findings had no statistically significant correlation with the incidence of micrometastases. The 5-year survival rates of patients with and without micrometastases were 94% and 89%, respectively. Similarly, the 10-year survival rates were 79% and 74%, respectively. The survival curves of patients with or without micrometastasis were nearly superimposed (P = 0.86).. The presence of immunohistochemically detected micrometastases in the regional lymph nodes did not affect the survival of Japanese patients with pT2N0M0 gastric carcinoma who had undergone gastrectomy with D2 lymph node dissection.

Topics: Adult; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Stomach Neoplasms; Survival Analysis

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

Our group has conducted several studies of sentinel node navigation surgery (SNNS) for the management of early gastric cancer. To determine the distribution of nodal metastases and micrometastases, we used immunohistochemical staining with anticytokeratin antibody to examine 2605 lymph nodes obtained from 108 consecutive patients with submucosal gastric cancer. When nodes were negative by routine hematoxylin and eosin (H&E) examination, micrometastases were confined to one regional lymphatic pathway near the primary tumor; however, when nodes were H&E-positive, micrometastases were distributed more widely. The wide and complicated lymphatic stream from a gastric tumor contributed to the relatively high (23%) incidence of micrometastases and the frequent occurrence of skip metastasis. In another study, we used a combination of blue dye and radiopharmaceutical to perform SNNS in 18 patients with early gastric cancer. The rate of sentinel node detection was 94%, and the average number of sentinel nodes per patient was three. Technical issues included size of particles, method of injection, accuracy of frozen section examination, and standard criteria for defining a sentinel node. SNNS for gastric cancer is a promising technique; further study of various anatomic and pathologic factors will indicate whether it can be used to determine the extent of lymphadenectomy necessary in patients with early gastric cancer.

Topics: Coloring Agents; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Radiopharmaceuticals; Sentinel Lymph Node Biopsy; Stomach Neoplasms

Micrometastases are considered to be a cause of recurrence after curative surgery for gastric cancer. It is important to clarify the clinicopathologic characteristics of micrometastases in the lymph nodes and peritoneal cavity to determine the treatment options in gastric cancer. Two consecutive sections of lymph nodes from patients with various cancers were examined by simultaneous staining with ordinary hematoxylin and eosin (H & E) and immunostaining with anti-cytokeratin antibody, respectively. Micrometastases in the lymph nodes were found in 18% of mucosal cancer, 25% of submucosal cancer, and 65% of T3 (serosal) cancers pecimens, with cancer-free nodes examined by H & E staining. A reduced 5-year survival rate was demonstrated in patients with nodal micrometastases among those with submucosal cancer and those with T3 cancer and cancer-free nodes examined by H & E staining. Molecular biological detection (MBD) of micrometastasis in lavage cytology specimens was performed by RT-PCR of carcinoembryonic antigen mRNA or telomerase activity assay. MBD protocols revealed micrometastases in cases with negative cytology results. Survival analysis demonstrated peritoneal recurrences in MBD-positive cases, whereas there was no recurrence in MBD-negative cases. Peritoneal micrometastases detected by MBD protocols appear to be a significant risk factor for recurrence. Therefore indications for lymph node dissection and postoperative chemotherapy should be determined based on the findings of micrometastases in gastric cancer.

Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Peritoneal Neoplasms; Prognosis; RNA, Messenger; Stomach Neoplasms; Survival Rate

The human monoclonal antibody SC-1 was isolated from a patient with a diffuse-type adenocarcinoma of the stomach using somatic cell hybridization. The immunoglobulin (Ig)M antibody reacts specifically with diffuse- (70%) and intestinal-type (25%) gastric adenocarcinoma and induces apoptosis in vitro and in vivo. When used in clinical trials with stomach carcinoma patients, significant apoptotic and regressive effects in primary tumors have been observed with the antibody SC-1. The SC-1 receptor is a new 82 kd membrane-bound isoform of glycosylphosphatidylinositol (GPI)-linked CD55 (decay-accelerating factor, DAF). CD55 is known to protect cells from lysis through autologous complement and is coexpressed with the ubiquitously distributed 70 kd isoform. The SC-1-specific CD55 isoform is up-regulated shortly after antibody binding, followed by an internalization of the antibody/receptor-complex, whereas the membranous expression of wild-type CD55 remains unchanged. The apoptotic process is marked by cleavage of cytokeratin 18, indicating the involvement of caspase-6 in the apoptotic process. In contrast to other apoptotic pathways, a cleavage of poly(ADP-ribose)polymerase (PARP) is not observed. The expression of the cell-cycle regulator c-myc becomes up-regulated, whereas expression of topoisomerase IIalpha is down-regulated. Induction of apoptosis leads to an increase in the internal Ca(2+) concentration, which is not necessary for the apoptotic process but for the transport of newly synthesized SC-1-specific CD55 isoform to the membrane.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Apoptosis; Calcium; Caspase 3; Caspase 6; Caspase Inhibitors; CD55 Antigens; Cell Membrane; Cytoplasm; Flow Cytometry; HeLa Cells; Humans; Keratins; Poly(ADP-ribose) Polymerases; Stomach Neoplasms

Cancer presumably arises from stem cells, preserved in an undifferentiated status since fetal development, or from a dedifferentiation of mature cells that return into a fetal phenotype with the potential for proliferation and renewal. Dedifferentiation in this context could represent a transient phase, passed through by cells, before they switch to redifferentiation, metaplasia or neoplasia. Cytokeratin-7 (CK7) is present in fetal, largely absent in normal adult, and transiently neoexpressed in metaplastic and neoplastic epithelial cells of the stomach according to previous observations. CK7 neoexpression in the stomach could, hence, define a fetal-like, dedifferentiated, cellular phenotype during the development of metaplasia and neoplasia. To test this hypothesis, we investigated CK7 expressions in fetal stomachs, non-neoplastic control stomachs, and neoplastic stomachs exhibiting metaplasia, intraepithelial neoplasia, and early cancer. Proliferation and beta-catenin expression of CK7-positive cells were also evaluated. The chronology of CK7 expression was studied during the experimental gastritis-cancer sequence in Mongolian gerbils. Our results show that metaplastic and neoplastic changes in the gastritis-cancer sequence are related to dedifferentiated epithelial cells which are defined by CK7 expression and can phenotypically be linked to fetal cells at the start of gastric pit development. The dedifferentiated cells exhibit a low proliferation and beta-catenin accumulation, similar to stem cells. Thus, the "stem cell" and "dedifferentiation" hypotheses for cancer origin could complement one another, and dedifferentiation-redifferentiation processes might be decisive for carcinogenesis in the stomach.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Carcinoma in Situ; Cell Transformation, Neoplastic; Child; Disease Models, Animal; Epithelial Cells; Female; Fetus; Gastric Mucosa; Gastritis; Gerbillinae; Gestational Age; Helicobacter Infections; Helicobacter pylori; Humans; Keratin-7; Keratins; Male; Metaplasia; Middle Aged; Stomach; Stomach Neoplasms

To study the distinctive clinicopathologic and immunohistochemical difference between ovarian metastatic carcinomas and primary ovarian carcinomas.. The clinical and pathological features of 27 cases of ovarian metastatic carcinomas (gastric carcinomas 12 cases, colon carcinomas 11 cases, others 4 cases) obtained from our department were reviewed. Immunostainings for CK (AE1/AE3), CK7, CK20, CEA, vimentin, nm23 were performed with SP staining methods.. On gross examination, metastasis from gastric adenocarcinoma were usually bilateral, while solid (11/12) and metastases from colonic adenocarcinoma were more often unilateral and cystic (7/11). Microscopically, metastases from gastric adenocarcinoma revealed signet ring cells or poorly differentiated adenocarcinomas (12/12), whereas metastases from colonic adenocarcinomas showed similar morphology of endometrioid adenocarcinoma (8/11). The majority of ovarian metastases of gastric carcinoma (7/12) and colon carcinoma (8/11) were CK20 positive. In particular, CK20 was invariably expressed in colon cancer metastases. Most of the ovarian metastatic carcinomas from the gastrointestinal tract failed to react with immunostaining of CK7. A combined use of CEA, vimentin and nm23 had made a correct classification for 11/12 cases of the gastric carcinoma, 10/11 cases of the colonic cancer.. CK7 and CK20 have been proved to be useful antibodies in distinguishing between metastatic carcinomas and primary carcinomas of the ovary. Combined use of a panel of antibodies can give more significant results.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Endometrioid; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Diagnosis, Differential; Female; Follow-Up Studies; Genes, Tumor Suppressor; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Ovarian Neoplasms; Stomach Neoplasms; Vimentin

It is important to clarify the clinicopathologic characteristics of micrometastasis in lymph nodes and microinvasion in primary lesions for the treatment options with regard to submucosal gastric cancer.. We examined 1945 lymph nodes and 68 primary tumors resected from 79 patients with submucosal gastric cancer. Two consecutive sections were prepared for simultaneous staining with ordinary hematoxylin and eosin and immunostaining with anticytokeratin antibody (CAM 5.2), respectively.. The incidence of nodal involvement in 79 patients with submucosal gastric cancer increased from 13% (10/79 patients) by hematoxylin and eosin staining to 34% (27/79 patients) by cytokeratin immunostaining. Micrometastases in the lymph nodes were found in 17 of 69 patients (25%), with cancer-free nodes examined by hematoxylin and eosin. Microinvasion to the muscularis propria was found in 11 of 68 patients (16%) who were histologically diagnosed with submucosal gastric cancer. Survival analysis demonstrated a lesser 5-year survival in the patients with micrometastasis in lymph nodes (82%) and with microinvasion to muscularis propria (73%). A high incidence of nodal involvement was found in submucosal cancers of large size (> 2 cm; 43%), a depressed type (48%), lymphatic invasion (73%), and deeper submucosal invasion (submucosal 3, 53%). A higher incidence of microinvasion was found with the diffuse-type carcinoma (33%).. Cytokeratin immunostaining is useful for detecting micrometastasis and microinvasion in submucosal gastric cancer. Tumor size, macroscopic type, lymphatic invasion, and the depth of submucosal invasion are strongly associated with lymph node involvement.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Coloring Agents; Eosine Yellowish-(YS); Female; Fluorescent Dyes; Gastric Mucosa; Hematoxylin; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Staining and Labeling; Stomach Neoplasms; Survival Analysis

We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma with respect to its histological classification and intrahepatic location (peripheral vs. hilar), and compared its profile with that of a variety of metastatic adenocarcinomas in liver.. Expression of cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers). Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic cholangiocarcinoma, respectively. Moderate and extensive expression of cytokeratin 18 was more frequent in the peripheral than in the hilar type. Moderate and extensive expression of cytokeratin 19 was seen in almost all cases of well-differentiated intrahepatic cholangiocarcinomas, while expression was decreased relatively in the moderately and decreased more in the poorly differentiated cases. While cytokeratin 20 was not found in non-neoplastic biliary epithelia or in well-differentiated intrahepatic cholangiocarcinomas, this cytokeratin was occasionally detectable in moderately and poorly differentiated intrahepatic cholangiocarcinomas and its expression was more frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree in those from gastric regions, and was rare in those from gallbladder and pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of metastatic colorectal and gastric carcinomas differed from that for intrahepatic cholangiocarcinomas, while that of metastatic gallbladder and pancreatic carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover, cytokeratin 18 and 19 expression was significantly infrequent in metastatic gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic colorectal carcinomas.. The combined immunostaining of cytokeratins 7, 18, 19 and 20 is useful for the characterization of intrahepatic cholangiocarcinomas with respect to histological subtypes and intrahepatic location. It helps to differentiate intrahepatic cholangiocarcinoma from metastatic adenocarcinomas in liver and from colorectal and gastric regions; it also indicates the primary focus metastatic adenocarcinomas in livers.

Topics: Adenocarcinoma; Biomarkers; Cholangiocarcinoma; Colorectal Neoplasms; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms

Colon signet ring cell adenocarcinomas are uncommon, high-grade neoplasms. Given their rarity, the question of primary colon or metastatic gastric adenocarcinoma frequently arises when signet ring cell carcinoma is seen in a colonoscopic biopsy or in biopsies procured from other regions of the body. A second related question regarding colon and gastric signet ring cell carcinomas is their immunophenotypic similarities with the glandular form of adenocarcinoma in each site. We studied the immunohistochemical phenotype of 14 colonic signet ring cell adenocarcinomas and compared them with immunophenotype of 27 gastric signet ring cell adenocarcinomas. We also compared the immunophenotype of the 27 gastric signet ring cell with the immunophenotype of 19 gastric gland-forming adenocarcinomas, and the immunophenotype of the 14 colonic signet ring cell adenocarcinomas to the immunophenotype of 20 colonic gland-forming adenocarcinomas to identify staining differences in the neoplastic cells of the two architectures. Antibodies studied were cytokeratins 7, 17, 19, and 20, CA 19-9, CA-125. estrogen receptor, and gross cystic disease fluid protein 15. Sixty-four percent of colon signet ring cell adenocarcinomas had either no staining or focal staining with cytokeratin 7 compared with diffuse staining in 63% of gastric signet ring cell adenocarcinomas (P = 0.016). Seventy-two percent of colon signet ring cell adenocarcinomas had diffuse staining with cytokeratin 20 compared with no or focal staining in 50% of gastric signet ring cell adenocarcinomas (P = 0.019). Fifty-seven percent of the colon signet ring cell adenocarcinomas had a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern compared with 11% of gastric signet ring cell adenocarcinomas (P = 0.004). Forty-four percent of gastric signet ring cell adenocarcinomas had a cytokeratin 7 (+)/cytokeratin 20 (-) pattern, compared with none of the colon signet ring cell adenocarcinomas (P = 0.004). The staining distribution of the antibody battery was similar in colon signet ring cell and colon glandular adenocarcinoma and gastric signet ring cell and gastric glandular adenocarcinomas. When signet ring cell adenocarcinoma is encountered in a colon biopsy, a colon primary is supported if the neoplastic cells have a cytokeratin 7 (-)/cytokeratin 20 (+) staining pattern, and a gastric primary is supported if they have a cytokeratin 7 (+)/cytokeratin 20 (-) staining pattern. The signet ring morphology at each site had an

Topics: Adenocarcinoma; Apolipoproteins; Apolipoproteins D; CA-125 Antigen; CA-19-9 Antigen; Carcinoma, Signet Ring Cell; Carrier Proteins; Colonic Neoplasms; Glycoproteins; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Membrane Transport Proteins; Receptors, Estrogen; Stomach Neoplasms

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

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

Cytokeratins (CKs) 19 and 20 have been used as targets for detecting cancer cells. We attempted to detect circulating cancer cells in patients with gastric cancer using a high-sensitivity reverse transcriptase-polymerase chain reaction (RT-PCR) assay for CK transcripts.. RT-PCR for CK 19 and CK 20 was performed on peripheral blood samples obtained from 52 patients with gastric cancer, from 24 of whom blood samples were collected on three occasions. Fourteen healthy volunteers served as controls.. CK 19 and CK 20 were positive in five (9.6%) of 52 patients with gastric cancer. Of these five, four were classified into stage IV and the other stage I, according to the TNM Classification. In gastric cancer patients, three (12.5%) were positive in the 24 cases examined three times and two (7.1%) were positive in 28 cases examined only once. Among the stage IV cancer, positive cases for CK showed significantly lower survival rates than those negative for CK. Between CK 19 and CK 20 in the 24 cases examined three times, CK 19 was found to be more sensitive in detecting cancer cells. CK 20 was detected in one (7.0%) of 14 healthy volunteers, whereas CK 19 was not detected.. We conclude that repeated blood sampling may be desirable to detect circulating cancer cells in peripheral blood, even in patients with advanced gastric cancer; CK 19 may be superior to CK 20 in detecting these cells. The clinical significance of detecting occult cancer in peripheral blood remains to be determined.

Topics: Biomarkers, Tumor; Humans; Intermediate Filament Proteins; Keratin-20; Keratins; Neoplastic Cells, Circulating; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Survival Rate

Based on the histological criteria proposed by the REAL and adopted by the WHO Classification, 30 cases of MALT type lymphoma, 18 cases of diffuse large B cell lymphoma (DLCL), and 17 cases of DLCLs, associated with a MALT type, were identified in a series of 65 surgically treated primary gastric lymphomas. The clinical records of the patients were analyzed retrospectively and the resected specimens were immunostained for bcl-2, p53 and Ki-67. Primary gastric DLBCLs, with or without a MALT type component, disclosed a higher stage of local extension, a more frequent nodal involvement and a significantly worse survival than pure MALT types. High p53 expression and high proliferation rate correlated with the presence of a large cell component and appeared useful for its identification in mixed forms. Low bcl-2 expression discriminated DLCL from DLCL/MALT. Tumor size, stage and Mib-1 index revealed a value in predicting prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Bacterial; Antigens, CD; Antigens, Nuclear; Biomarkers, Tumor; Combined Modality Therapy; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Italy; Keratins; Ki-67 Antigen; Life Tables; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Phenotype; Proto-Oncogene Proteins c-bcl-2; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tumor Suppressor Protein p53

To define lymph node micrometastasis and to investigate the difference between micrometastasis and microinvolvement.. A total of 1,087 regional lymph nodes were collected from surgical specimens of 17 patients with gastric carcinoma. 71 nodes were found to contain microlesions, 60 sections per node) and immunohistochemistical staining for CK18, EMA and SAM. Another 20 nodes containing macrometastasis were also studied.. After serial sections, the microlesions disappeared in 34% (24 nodes), increased in 49% (35 nodes), microlesions transformed into macrometastasis in 17% (12 nodes). Microlesions presented as a cluster of tumor cells (

Topics: Actins; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Mucin-1; Muscle, Smooth; Stomach Neoplasms; Stromal Cells

Metastatic adenocarcinoma in the liver with an unidentified primary tumor site is a common clinical problem. Pathologists often are asked to identify the primary tumor site. The histologic picture itself usually is not helpful, because the histology may be similar in the metastases of tumors with different primary localizations. Immunohistochemistry can be helpful, but the previously recommended antibody panels are too complicated for everyday use.. A simple immunohistochemical algorithm with two monoclonal cytokeratin (CK) antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas metastatic to the liver. Sections of the liver metastases were stained automatically and evaluated as negative (no staining), focally positive, or diffusely positive. Statistical comparison of the staining results for a single antibody was calculated as an odds ratio.. Thirty-six of 93 (39%) metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative (-) pattern was highly characteristic for colorectal localization of the primary tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern of the metastatic liver adenocarcinomas was highly suggestive of primary localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of the tumors originating in the stomach raised these values to 94% and 92%, respectively. The statistically calculated predicted probability of primary tumor site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the probability of a primary tumor being located in the pancreas or biliary tract was 74,85%, if calculated for the whole study group.. The tested simple algorithm proved to be useful in CK20 positive (+) cases, predicting a primary tumor localization in the colon, rectum, pancreas, or biliary tract with high accuracy. The CK20- group was too heterogeneous to be classified adequately by these two antibodies.

Topics: Adenocarcinoma; Algorithms; Colorectal Neoplasms; Female; Gallbladder Neoplasms; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Liver Neoplasms; Male; Neoplasms, Unknown Primary; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms

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

BAG-1 is a Hsp70/Hsc70-binding protein that interacts with Bcl-2, Raf-1, steroid hormone receptors, Siah-1, and hepatocyte growth factor (HGF) receptors, implying multiple functions for the BAG-1 protein. Here, we provide evidence that gene transfer-mediated overexpression of BAG-1 markedly enhances the motility of human gastric cancer cells. Two independent in vitro migration assays showed that the BAG-1-expressing MKN74 cells exhibited more active migration compared with control transfectants or parent MKN74 cells. In MKN74 cells, the overexpression of BAG-1 affected neither cell adhesion capability nor migration responses to HGF. The promotive effect of BAG-1 on cell migration was similarly observed in transfectants of another human gastric cancer MKN45 cell line. In BAG-1 transfected gastric cancer MKN74 cells, BAG-1 colocalized with cytokeratin as well as actin filaments, and was concentrated at membrane ruffles induced by lysophosphatidic acid (LPA). Taken together, these studies demonstrate that BAG-1 has a novel function as promoter of cell migration in human gastric cancer cells, possibly through cooperation with cytoskeletal proteins.

Topics: Actins; Animals; Carrier Proteins; Cell Adhesion; Cell Movement; Culture Media; DNA-Binding Proteins; Humans; Keratins; Mice; Serum Albumin, Bovine; Stomach Neoplasms; Transcription Factors; Tumor Cells, Cultured

Although the tyramine amplification technique to enhance sensitivity in immunohistochemistry has been described in numerous methodological papers, it has not yet gained access to diagnostic immunohistochemistry. This is mainly due to problems and pitfalls occurring in adaptation of this method to routine application. In this study a monoclonal antibody and a polyclonal antiserum (pan-cytokeratin and anti-myoglobin) were tested in tissues with different amounts of epitopes, using a checkerboard table and testing a total of 133 different dilution combinations of both the tyramide solution and the primary antibodies. The specific tissue investigated, i.e. the amount of accessible epitope to be detected and the applied concentration of the tyramide solution mainly influenced the staining reaction. Several pitfalls such as an uneven distribution of the staining or dramatic overstaining (paradoxical overstaining) must be considered to achieve optimal results. In conclusion, our data confirm methodological studies that the tyramine amplification technique is a powerful method to enhance immunohistochemical sensitivity. However, for reliable daily practice several pitfalls of the technique have to be circumvented.

Topics: Antibodies, Monoclonal; Epitopes; Gastric Mucosa; Humans; Immune Sera; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Microscopy, Electron; Muscle, Skeletal; Myoglobin; Staining and Labeling; Stomach Neoplasms; Tyramine

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

Cytokeratin (CK) immunohistochemistry revealed changes in the CK19 immunoreactivity in human gastrointestinal epithelium during embryonic and fetal development. These changes were particularly marked in the jejunum and ileum. CK19 immunoreactivity was strong up to the 11th week of pregnancy, but was absent between weeks 12 and 17, and reappeared weakly from week 18 to week 24. This temporal pattern correlated with that of cell proliferation investigated by immunohistochemical detection of proliferating cell nuclear antigen. Marked CK expression was associated with a low proliferative rate and vice versa. To test whether these results were relevant to the assessment of intestinal metaplasia and the risk of malignant transformation with poor cell differentiation, adenomas and adenocarcinomas of the colon, intestinal metaplasia of the stomach, and two types of gastric carcinoma were also examined by CK19 immunohistochemistry. Substantial CK19 immunoreactivity was found in well-differentiated cancers and low-grade dysplasias with low cell proliferation, whereas only weak CK19 immunoreactivity was found in poorly differentiated carcinomas and high-grade dysplasias with a high proliferation rate.

Topics: Adenocarcinoma; Aging; Cell Differentiation; Cell Division; Colonic Neoplasms; Gastric Mucosa; Gastrointestinal Neoplasms; Humans; Ileum; Immunohistochemistry; Jejunum; Keratins; Proliferating Cell Nuclear Antigen; Reference Values; Stomach; Stomach Neoplasms

Among 474 cases of gastric carcinoma studied in gastrectomy specimens from 1990 to 1996, only one (0.21%) showed positivity for vimentin. It was located on a gastric stump and, endoscopically, the tumor was classified as early gastric carcinoma type IIb + IIc. Histologically, tumor cells were extensively round to polygonal and had eosinophilic, or clear cytoplasm; the nuclei were large with conspicuous nucleoli. In some areas, the cytoplasm showed vimentin and(or cytokeratin coexpression by double immunostaining. Our results and the patient's rapid deterioration (death occurred six months after surgery) suggest that this type of tumor, although diagnosed as early carcinoma, behaved like an advanced malignancy.

Topics: Biomarkers, Tumor; Carcinoma; Cell Separation; DNA, Neoplasm; Fatal Outcome; Flow Cytometry; Gastrectomy; Gastric Stump; Humans; Inclusion Bodies; Keratins; Male; Middle Aged; Organelles; Ploidies; Rhabdoid Tumor; Stomach Neoplasms; Vimentin

We looked for disseminated tumour cells postoperatively in the bone marrow of 22 patients with gastric cancer and of 26 patients with colorectal cancer. On an average the follow-up was 6.5 months in the gastric cancer group and 9 months in the colorectal cancer group. In 27% of the gastric cancer group and in 30% of the colorectal cancer group follow-up aspirates were obtained. Micrometastases were detected in 96% of colorectal cancer patients and in 77% of gastric cancer patients. Both, postoperative and follow-up aspirations showed clear differences in the number of ck+ cells between the iliac crest sides. The majority of cells formed clusters from 2 to about 200 cells. In both groups no significant correlation was found between the number of tumour cells detected and the established risk factors (stage, tumour extension, lymph node involvement, distant metastasis) or the disease-free survival. In the gastric cancer group higher numbers of ck+ cells were seen in the low tumor stages I and II, as compared to stage III and IV. Besides, in this group significantly more ck+ cells were detected in younger patients (age under 63,5) than in the older group over 63,5 years. Colorectal cancer patients did not show this correlation. In follow-up aspirations the number of ck+ cells of the colorectal and also the gastric cancer group showed a tendency of rise in relapse and of fall in disease-free survival. There was a tendency of higher rates of ck+ cells in the colorectal cancer group when compared to gastric cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Marrow Cells; Bone Marrow Examination; Bone Marrow Neoplasms; Colorectal Neoplasms; Disease Progression; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Risk Factors; Statistics as Topic; Stomach Neoplasms

We have established two Epstein-Barr virus (EBV)-positive cell lines, GT38 and GT39, derived from human gastric tissues of two patients bearing gastric carcinoma. Both cell lines were positive for cytokeratin, an epithelial marker, but not for lymphocyte-related markers. Unlike GT39 cell line, GT38 cells lacked the property of contact inhibition. EBV genome was detected in both cell lines. The cell lines were positive for latent membrane protein 1, and EBV-determined nuclear antigen 1 (EBNA1). EBNA2 was also detected in GT38. These cell lines should be useful for studying the interaction of EBV with gastric epithelial cells and its role in gastric carcinogenesis.

Topics: Cell Line; Epithelium; Epstein-Barr Virus Nuclear Antigens; Genome, Viral; Herpesvirus 4, Human; Humans; Keratins; Oncogene Proteins, Viral; Stomach Neoplasms; Viral Matrix Proteins

In humans, low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach regress when Helicobacter pylori infection is cured by antimicrobial therapy. Using an animal model of human gastric MALT lymphoma, we observed the effects of Helicobacter felis eradication and the relationship between infection and disease progression. Antimicrobial therapy was given to one-half of the BALB/c mice infected with H. felis for 20 months. Groups of antibiotic-treated and untreated mice were killed 2, 3, and 4 months after antimicrobial therapy (ie, 22, 23, and 24 months after infection). The numbers of mice with MALT decreased after H. felis eradication with no lymphoid follicles seen 4 months after treatment. MALT lymphoma was present in a total of 23% (11/48) of antibiotic-treated infected mice compared with 75% (27/36) in untreated infected mice. These lymphomas were further graded into low-, intermediate-, and high-grade lymphoma. In the untreated mice, lymphoma development was more advanced with 36% low-grade (13/36), 39% intermediate-grade (14/36), and 6% high-grade (large B-cell) lymphoma (2/36) whereas in the treated mice the incidence was 21% (10/48), 6% (3/48), and 0% (0/48), respectively. These observations suggest that antigenic stimulation by H. felis sustained growth and progression of low-grade MALT lymphoma and that primary high-grade gastric lymphomas can evolve from the transformation of these tumors. Eradication of the organism caused low-grade tumors to regress, with inhibition or slowing down of lymphoma development toward high-grade lymphoma. The H. felis mouse model of gastric MALT lymphoma presents an opportunity to address the issues arising from antimicrobial treatment of these tumors in humans.

Topics: Animals; Anti-Bacterial Agents; CD3 Complex; Female; Helicobacter Infections; Immunohistochemistry; Keratins; Lymphoma, B-Cell, Marginal Zone; Mice; Mice, Inbred BALB C; Specific Pathogen-Free Organisms; Stomach Neoplasms; Time Factors

In a subset of patients with early gastric cancer, there were recurrences of the disease after a curative resection had been done. Direct evidence of tumor seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap because it is a feature of epithelial cells that would not normally be present in bone marrow. From 1994-1997, the bone marrow of 45 patients with early gastric cancer was examined for tumor cells, using immunocytochemical techniques and an antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. Clinicopathological characteristics were determined for subjects with cytokeratin-positive cells in the bone marrow. Of these 45 patients, 9 (20.0%) had cytokeratin-positive cells in the bone marrow at the time of primary surgery. These positive findings were not related to tumor advance-related factors of lymph node metastasis and distinct lymphatic and vascular invasion. Microvessel density in the primary tumor exceeded 2-fold in cytokeratin-positive cells, compared with findings in negative cells (P < 0.05). Tumor cells in bone marrow are indicative of the general disseminative metastasis in patients with early gastric cancer, and the metastatic potential was closely related to angiogenesis in the primary tumor.

Topics: Aged; Antibodies, Monoclonal; Bone Marrow Neoplasms; Female; Gastric Mucosa; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Stomach Neoplasms

To assess the role of cytokeratin 7 monoclonal antibody in the differential diagnosis of primary ovarian carcinoma and metastatic ovarian carcinoma originated from the gastrointestinal tract.. Immunohistochemical study using cytokeratin 7 monoclonal antibody and ABC kit.. All the 46 cases of primary ovarian carcinoma were CK 7 positive, while in the metastatic ovarian carcinoma of intestinal origin, all cases remained negative for CK7. Half of the 34 cases of metastatic ovarian carcinoma of gastric origin were CK 7 positive. The positive result of CK7 was significantly higher in the primary ovarian carcinoma than in each group of the metastatic ovarian carcinoma (P < 0.001).. CK 7 is seemed to be a useful antibody in the differential diagnosis of ovarian carcinoma.

Topics: Antibodies, Monoclonal; Carcinoma, Endometrioid; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Intestinal Neoplasms; Keratin-7; Keratins; Ovarian Neoplasms; Stomach Neoplasms

Phenotyping of cytokeratin (CK)18-positive cells in bone marrow is gaining increasing importance for future prognostic screening of carcinoma patients. Urokinase-type plasminogen activator receptor (uPA-R) is one example of a potential aggressive marker for those cells. However, a valid and reliable double staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18-positive tumor cell controls exhibited black uPA-R staining in 15-80% of cases and red CK18 staining in almost 100% of tumor cells. Isotype- and cross-matched controls were completely negative. Bone marrow from healthy donors was always CK18-negative. Reproducibility of CK18-positive cell detection was estimated in a series of specimens from 61 gastric cancer patients comparatively stained with the single alkaline phosphatase-anti-alkaline phosphatase (APAAP) and our double staining method (10(6) bone marrow cells/patient). In four cases, double staining could not reproduce CK18-positive cells. In 34 cases it revealed fewer or equal numbers, and in 23 cases more CK18-positive cells than the APAAP method. Overall quantitative analysis of detected cell numbers (838 in APAAP, range 1-280 in 10(6); double staining 808, range 0-253) demonstrated relative reproducibility of APAAP results by double staining of 97%. Correlation of results between both methods was significant (p < 0.001, linear regression). Sensitivity of double staining tested in logarithmic tumor cell dilutions was one CK18-positive cell in 300,000. Specific uPA-R staining was seen on CK18-positive cells in bone marrow from 29 of 61 patients, and also on single surrounding bone marrow cells. To test the specificity of this staining, bone marrow cytospins from 10 patients without tumor disease were stained for uPA-R with the APAAP method. uPA-R expression was confirmed in all 10 cases, with a mean of 6.5% uPA-R-positive cells in 1000 bone marrow cells (SEM 1.2%). These results suggest that our double staining protocol is a sensitive, reproducible, and specific method for routine uPA-R phenotyping of disseminated CK18-positive cells in bone marrow of carcinoma patients.

Topics: Alkaline Phosphatase; Bone Marrow Neoplasms; Enzyme Precursors; Humans; Keratins; Phenotype; Plasminogen Activators; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Sensitivity and Specificity; Staining and Labeling; Stomach Neoplasms; Urokinase-Type Plasminogen Activator

Phenotypic expression of keratin polypeptides is known to be dependent on various factors, one of which is malignant transformation. In this study, we compared the pattern of expression of keratin polypeptides between control and malignant gastric tissues by employing different morphological and biochemical techniques. The results indicated preferential decrease of acidic keratin polypeptides in malignant gastric tissues. The nonmalignant gastric tissues expressed four keratin polypeptides-two acidic and two basic-whereas in the gastric adenocarcinomas expression of only two basic polypeptides was observed. Marked variation of keratin expression between the control and malignant gastric tissues not only highlights its clinical value as a support to diagnosis but also elucidates the underlying changes due to malignant transformation.

Topics: Adenocarcinoma; Adult; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Humans; Keratins; Neoplasm Proteins; Peptide Biosynthesis; Peptides; Stomach Diseases; Stomach Neoplasms

Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19 mRNA was applied to detect circulating cancer cells in the peripheral and portal blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in peripheral and/or portal blood samples from patients with pancreatic cancer (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50 healthy volunteers served as controls. RT-PCR was conducted in duplicate in each sample, and only samples showing keratin 19 transcript in both determinations were considered as being positive. All the pancreatic and gastric cancers, but none of the control blood samples, were found to be positive. Dilution study using pancreatic cancer cells serially mixed against peripheral blood showed that detection sensitivity was more than one cancer cell in 10(6) peripheral blood mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal blood samples gave positive results in one stage III and one stage IV patient, and that of peripheral blood samples gave positive results in 2 stage IV patients. No positive results were obtained in any of the blood samples from gastric cancer patients. Our results indicate that incidence of circulating cancer cells is unexpectedly very low even in advanced pancreatic and gastric cancer patients.

Topics: Humans; Keratins; Neoplasm Staging; Pancreatic Neoplasms; Polymerase Chain Reaction; Portal Vein; RNA-Directed DNA Polymerase; RNA, Messenger; Stomach Neoplasms

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

We describe the case of a 73-year-old patient with gastric adenocarcinoma composed of histologically well differentiated glandular areas, extensive rhabdoid zones and regions depicting a transition between these two constituents. The rhabdoid component showed typical features such as abundant eosinophilic cytoplasm, eccentric nuclei, prominent nucleoli, intense positive immunohistochemical cytoplasmic reaction for vimentin and less evident immunohistochemical for cytokeratin and epithelial membrane antigen (EMA). Our findings strongly suggest that the rhabdoid areas probably represent a phenotypic variant of a gastric adenocarcinoma, otherwise fairly well differentiated, a combination that to the best of our knowledge has not been previously reported.

Topics: Actins; Adenocarcinoma; Aged; Carcinoembryonic Antigen; Cell Transformation, Neoplastic; Desmin; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Rhabdoid Tumor; Stomach Neoplasms; Vimentin

To evaluate DNA/Cytokeratin(CK) multiparametric method in detection to the gastric cancer and to study the relations of cellular DNA content, S-phase fraction (SPF) and G2/M-phase fraction (G2/MPF) to lymph node (LN) metastasis.. 50 cases of fresh tumor samples, were examined by using single (DNA) and two-colored DNA/CK flow cytometry respectively.. The rate of aneuploid, the mean and the range of SPF and G2/MPF were higher in the multiparametric method than that in single one. In aneuploid carcinoma, the incidence of LN metastasis was significantly higher, the G2/MPF values with LN metastasis were higher than those without metastasis; values were higher in metastasis to n2 or n3 than that to n1. The SPF or G2/MPF values correlated with the number of LN metastasis, being significantly higher in metastasis to 5 LN than to 1-4 LN.. Multiparametric DNA/CK cytometric analysis is better than single DNA one; correlations between cellular DNA content, SPF, G2/MPF and the extent of LN matastasis exist.

Topics: Adult; Aged; Aneuploidy; Cell Cycle; DNA, Neoplasm; Female; Flow Cytometry; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Stomach Neoplasms

Direct evidence of tumour seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap since it is a feature of epithelial cells that would not normally be present in bone marrow. The bone marrow of 46 patients with primary gastric cancer was examined for tumour cells, using immunocytochemical techniques and antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. The monoclonal antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no. 18) commonly present in epithelial cells. The expression of tumour-suppressor genes p53 and RB for the primary lesion was also determined using the monoclonal antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the time of primary surgery. The positive findings were related to the undifferentiated tissue type and to the prominent depth of invasion, but not to other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of invasion was limited to the mucosa. The metastatic potential to bone marrow did not relate to expressions of p53 and RB genes, or to the proliferating activity of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in bone marrow are indicative of the general disseminative capability of an individual tumour, this technique may be useful for identifying patients at high risk of metastasis from a gastric tumour.

Topics: Antibodies, Monoclonal; Bone Marrow; Cell Division; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Metastasis; Retinoblastoma Protein; Stomach Neoplasms; Tumor Suppressor Protein p53

Epstein-Barr virus (EBV)-associated gastric carcinomas have been reported from various regions of the world. Epstein-Barr virus appears to be pathogenetically related to some gastric carcinomas. To determine the incidence of EBV association with gastric carcinomas among Koreans, the authors have studied EBV genome expression in 89 consecutive patients with gastric carcinomas diagnosed at the Catholic University Hospitals in Seoul, Korea, using in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs), and immunohistochemistry for EBV latent membrane proteins (LMP) and CD21 antigen on paraffin sections. Thirty-seven gastric specimens with benign ulcer disease were used controls. EBV-encoded small RNAs were expressed in tumor cell nuclei in 12 patients (13.5%). None of the controls or benign portions of the cases were positive. In the positive cases, all tumor cell nuclei were uniformly stained and the staining intensity was strong. Immunohistochemistry for LMP was positive in 3 of 12 EBERs positive patients and none of EBERs negative patients. EBV latent membrane proteins was localized only in the lymphoid cells infiltrating the tumor in two patients, and tumor cells as well as infiltrating lymphoid cells in one patient. These results indicate that the rate of EBV association with gastric carcinomas in Koreans is relatively high and comparable to other Far Eastern Asian regions. The expression pattern in EBV-associated gastric carcinomas is similar to those of nasopharyngeal carcinomas in which clonality analysis using specific probes to the tandem repeat region of EBV yielded single episomal bands suggesting that EBV infection in EBV-associated gastric carcinomas are also clonal and pathogenetically related to the neoplasm. However, the mechanism of tumorigenesis remains to be elucidated.

Topics: Adenocarcinoma; Adult; Aged; DNA, Viral; Female; Genes, Viral; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Korea; Male; Middle Aged; Receptors, Complement 3d; Retrospective Studies; RNA, Viral; Stomach Neoplasms; Tumor Virus Infections; Viral Matrix Proteins

Even after curative resection of an early gastric cancer, some patients die of a recurrence. It is our view that patients with early gastric cancer who died of their disease had occult micrometastases in perigastric lymph nodes at the time of the original diagnosis. In an attempt to identify these micrometastases, lymph nodes dissected from early gastric cancer lesions were stained after operation with monoclonal antibody against cytokeratin, an essential constituent of the cytoskeleton of epithelial cells.. The 420 dissected lymph nodes from 34 patients with node-negative early gastric cancer who died of a recurrence were examined for the presence of tumor cells. We used immunocytochemical techniques and an antiserum to epithelial membrane antigen. The monoclonal antibody CAM 5.2 recognizes cytokeratin polypeptides (human cytokeratin numbers 8 and 18) commonly present in epithelial cells. Clinicopathologic characteristics and prognosis were determined for patients with cytokeratin-positive cells in the lymph nodes. RESULTS. Of 420 lymph nodes, 15 (3.6%) nodes and 23.5% (8 of 34) of the patients presented with cytokeratin-positive cells at the time of primary operation. The presence of cytokeratin positivity was not related to various clinicopathologic factors. The histologic stage of eight cytokeratin-positive cases was upstaged by the group of cytokeratin-positive lymph nodes from stage I to three of stage II, four of stage III, and one of stage IV, hematogenous recurrences were common, and the prognosis was poorer.. Immunohistochemical techniques aid in identifying micrometastatic disease in lymph nodes missed in routine hematoxylin-eosin staining. Cytokeratin staining of the dissected lymph nodes is recommended to precisely determine tumor stage and prognosis for patients with early gastric cancer.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Stomach Neoplasms; Survival Rate

We studied the clinical significance of the soluble cytokeratin 19 fragment detected with monoclonal antibody CYFRA 21-1 in the sera of patients with histologically proven gastric cancer. Sera of 110 patients with gastric cancer were analysed for CYFRA 21-1 levels by a two-step sandwich enzyme immunoassay. There were no significant differences between CYFRA 21-1 levels and the histotype, depth of invasion or vessel invasion. However, CYFRA 21-1 was significantly higher in the presence of peritoneal metastases, liver metastases and extensive nodal involvement. When the positive cut-off value was defined as 5 ng ml-1, the CYFRA 21-1 in the stage IV and recurrent cases was 55.6% and 66.7%, respectively, which was as high as carcinoembryonic antigen (CEA) and greater than carbohydrate antigen 19-9 (CA 19-9). The positivities in stage I/II and III were zero and 5.9%, respectively, and false-positive rate in 76 patients with benign gastrointestinal disorders was 2.6%. There appeared to be no correlation between CYFRA 21-1 and CEA or CA 19-9. The patients with above 5 n ml-1 of CYFRA 21-1 had a significantly poorer prognosis. Multivariate analysis indicated that CYFRA 21-1 was an independent prognostic factor, while CEA and CA 19-9 failed to be of prognostic value. In conclusion, CYFRA 21-1 is a reliable tumour marker for gastic cancer in predicting very advanced cases, recurrence of the disease and overall poor prognosis.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Recurrence, Local; Neoplasm Staging; Peptide Fragments; Prognosis; Stomach Neoplasms

A sensitive method for the detection of gastric cancer micrometastases in lymph nodes was developed. The method was based on amplification of keratin 19 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Keratin 19 RT-PCR showed that keratin 19 mRNA was expressed in all 12 gastric cancers, but not in any of 20 normal control lymph nodes, indicating that keratin 19 mRNA is a good target of RT-PCR for the detection of gastric cancer micrometastases in lymph nodes. Serial dilution studies of RNA extracted from gastric cancers against RNA extracted from control lymph nodes demonstrated that the detection sensitivity of the keratin 19 RT-PCR method was one cancer cell in 10(3)-10(5) lymph node cells. Detectability of lymph node metastases was compared between keratin 19 RT-PCR and conventional histological examination, using 100 lymph nodes obtained from 12 gastric cancer patients. Keratin 19 mRNA was detected in all of the seven lymph nodes which were histologically metastasis-positive. Of the 93 lymph nodes which were histologically metastasis-negative, 79 were found not to express keratin 19 mRNA but 14 were found to express keratin 19 mRNA, indicating that these lymph nodes contained micrometastases which could not be detected by histological examination. These results demonstrate that keratin 19 RT-PCR is a more sensitive method than histological examination for the detection of gastric micrometastases in lymph nodes.

Topics: Adult; Aged; Aged, 80 and over; Base Sequence; Female; Gene Expression; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; RNA-Directed DNA Polymerase; RNA, Messenger; Sensitivity and Specificity; Stomach Neoplasms

Topics: Adenocarcinoma; Cardia; Duodenal Neoplasms; Duodenoscopy; Gastroscopy; Humans; Keratins; Male; Middle Aged; Mucins; Pyloric Antrum; Stomach Neoplasms

The expression of the cytokeratins (CK) 1, 5, 6, 7, 10, 13 and 14 was studied immunohistochemically in gastric biopsies from both the antrum and the body of 70 patients. Normal gastric foveolar epithelium (9 cases) Helicobacter pylori gastritis (23) and intestinal metaplasia (38) were examined. Positive staining results for CK 1, 5, 10 and 14 were not observed using the 34 beta E12 antibody. With antibodies to CK 5/6, 7 and 13 some, but not all cases, were immunoreactive. Predominantly positive staining included less than 10% of the cells and was always restricted to the tips and the juxtaluminal areas of the foveolae. No difference was seen between the antrum and the body. Comparing normal gastric mucosa with gastritis and intestinal metaplasia, cases positive for CK 5/6 were observed less frequently in intestinal metaplasia types II and II compared to the other groups. CK 7 was expressed exclusively in intestinal metaplasia. CK 13 was seen in all groups of specimens. Thus, cytokeratins typical for ductal structures (CK 7) and squamous epithelia (CK 5/6, CK 13) can be regarded as an inconstant, but not unusual observation in the gastric mucosa. Their expression may be controlled by both differentiation-related as well as environmental factors.

Topics: Adult; Carcinoma, Squamous Cell; Epithelium; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Neoplasms; Keratins; Male; Middle Aged; Pyloric Antrum; Stomach Neoplasms

Recently, the expression of vimentin has been reported in some carcinomas. This study was designed to clarify the significance of vimentin expression in solid type poorly differentiated adenocarcinomas of the stomach. Immunohistochemically, 239 poorly differentiated adenocarcinomas with solid components of the stomach were stained for vimentin. Vimentin-positive cases were also stained by CAM 5.2 using serial mirror sections. We found 15(6.3%) vimentin-positive cases. Twelve of them demonstrated varying amounts of rhabdoid-like cells. Eight cases diffusely co-expressed vimentin and cytokeratin simultaneously. In addition, four co-expressing cases showed positive staining with Keratin-903 which recognizes the high molecular-weight cytokeratin. Most of the co-expressing cases showed a diffuse proliferation of polygonal tumour cells with focal cell-to-cell contact. The prognosis of the co-expressing cases was poor in comparison with that of the 89 vimentin-negative tumours (P < 0.05).

Topics: Adenocarcinoma; Adult; Aged; Biomarkers; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Prognosis; Stomach Neoplasms; Survival Analysis; Vimentin

Topics: Biomarkers, Tumor; Gastrectomy; Humans; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Retrospective Studies; Stomach Neoplasms

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

Tautomycin isolated from Streptomyces spiroverticillatus is an inhibitor of protein phosphatases 1 and 2A. Tautomycin induced hyperphosphorylation of cytokeratin peptides in human keratinocytes (PHK 16-I cells) 30 times less strongly than did okadaic acid. Repeated applications of tautomycin (30 micrograms, 40 nmol/application) did not induce tumor promotion in a two-stage carcinogenesis experiment on mouse skin initiated with 7,12-dimethylbenz[a]anthracene, whereas okadaic acid (1 microgram, 1.2 nmol/application) as a control induced tumor promotion strongly. As for mucosa of rat glandular stomach, tautomycin induced ornithine decarboxylase 4 h after intubation into the stomach. The tumor-promoting activity of tautomycin was next studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administration of tautomycin in the diet (1 mg rat-1 day-1), from week 9 to week 52 of the experiment, inhibited rather than enhanced tumor development in the glandular stomach initiated with MNNG. The percentages of tumor-bearing rats of the groups treated with MNNG plus tautomycin, MNNG alone, and tautomycin alone were 20.0%, 40.6%, and 0% respectively in week 52. The reason for the absence of tumor-promoting activity of tautomycin was studied in relation to tumor necrosis factor alpha (TNF alpha), an endogenous tumor promoter. We found that tautomycin neither enhanced TNF alpha mRNA expression in mouse skin nor induced TNF alpha release in a human stomach cancer cell line (KATO III cells), whereas okadaic acid did both. These results indicate that not all inhibitors of protein phosphatases are tumor promoters, and suggest that tumor promotion of the okadaic acid class of compounds is mediated by TNF alpha.

Topics: Animals; Antifungal Agents; Carcinogens; Enzyme Induction; Enzyme Inhibitors; Ethers, Cyclic; Female; Gene Expression; Humans; Keratins; Male; Mice; Okadaic Acid; Ornithine Decarboxylase; Phosphoprotein Phosphatases; Phosphorylation; Pyrans; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Spiro Compounds; Stomach Neoplasms; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Keratin is a member of the intermediate filament family in epithelial cells. Two-dimensional gel electrophoresis of different epithelial cells has shown 20 different keratin polypeptides. Therefore, mapping of the keratin polypeptides can be used to define a specific tissue.. Cytokeratin expression was investigated by using monoclonal antibodies in human surgical specimens and autopsy material of pancreatic, gastric, liver, and colon carcinomas and cholangiocarcinomas, and their metastasis to lymph nodes and liver was examined. In addition, rat acinar cell carcinomas were used to compare cytokeratin expression in ductal vs. acinar cell pancreatic carcinomas.. Human pancreatic ductal carcinomas expressed keratins 7, 8, 18, and 19, whereas the majority of rat acinar carcinomas did not express keratins typical for ducts in rat pancreas. The keratin patterns of gastric and colon carcinomas were identical with keratins 8, 18, and 19. In contrast, hepatocellular carcinomas expressed the same keratin pattern as pancreatic acinar carcinomas with keratins 8 and 18, whereas cholangiocarcinomas expressed keratin 7, 8, 18, and 19, similar to pancreatic ductal carcinomas. Metastasis of pancreatic ductal and colon carcinomas retained their keratin patterns.. Keratin polypeptide typing of unknown malignant cells can be a useful tool for cell identification.

Topics: Animals; Azaserine; Carcinoma, Acinar Cell; Carcinoma, Ductal, Breast; Colonic Neoplasms; Epithelium; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Neoplasms, Experimental; Pancreatic Neoplasms; Rats; Rats, Inbred Lew; Stomach Neoplasms

Topics: Biomarkers, Tumor; Biopsy; Cell Transformation, Neoplastic; Gastric Mucosa; Gastritis; Gastroscopy; Humans; Keratins; Metaplasia; Polyps; Precancerous Conditions; Stomach Neoplasms; Stomach Ulcer

We studied 71 patients with solid-type gastric adenocarcinoma selected from 5,437 surgically resected specimens during the period from 1975 to 1988; six had vimentin-positive adenocarcinomas, and five of these were advanced. One was at an early stage. All six tumors showed the same histologic features and had either a diffuse or alveolar arrangement, with tumor cells having either poor or no cohesiveness. Many tumor cells were round to polygonal, with eosinophilic or clear cytoplasm and large, eccentric vesicular nuclei, as seen in malignant rhabdoid tumors of the kidney. In all cases, the cytoplasm showed coexpression of vimentin and cytokeratin as revealed by double immunostaining. Four of the five cases with advanced carcinoma died of the disease 1 to 6 months after surgery. The cases with vimentin-positive tumors had significantly poorer prognoses than those with vimentin-negative tumors. We also studied adenocarcinomas of various histologic types randomly selected from our file (160 intestinal type and 69 diffuse type of Lauren) but failed to detect any vimentin positive ones. These results indicate that vimentin is expressed in some of the solid-type adenocarcinomas, which have a poor prognosis, and indicating that rhabdoid-like cells may be found in a variety of adenocarcinomas of the stomach.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Cell Nucleus; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Prognosis; Stomach Neoplasms; Vimentin

The finding of cytokeratin positivity in non-epithelial cells in 9/15 cases of performing or penetrating gastric ulcer is reported. Two different monoclonal anti-cytokeratin antibodies were used and both produced a strong positivity in spindle and polyglonal cells in the gastric wall. These cells were often distributed near the peritoneal surface, but they were also found in central parts of the gastric wall. The cytokeratin-positive cells had no connection with the gastric mucosa, lacked epithelial features in routinely stained sections and were not positively stained by antibodies to other epithelial markers (EMA and Ber-Ep 4). Many of the cytokeratin-positive cells were also positive for vimentin. There was no evidence of malignancy in any of the cases, but cytokeratin-positive cells like those in the present study may be erroneously interpreted as infiltrating carcinoma. The true nature of the cytokeratin-positive cells was not revealed in the present study. It is concluded that cytokeratin positivity must be evaluated with care and that it is valuable to add antibodies other than anti-cytokeratins for the recognition of epithelial cell differentiation.

Topics: Antibodies, Monoclonal; Cell Transformation, Neoplastic; Gastric Mucosa; Humans; Immunohistochemistry; Keratins; Stomach; Stomach Neoplasms; Stomach Ulcer; Vimentin

We developed a new and automated assay for the detection of lung cancer associated cytokeratin 19 fragments in patients' sera/plasma. This new tumour marker assay CYFRA 21-1 was evaluated in technical and clinical studies using the multibatch analysers ES 300 and ES 600 from Boehringer Mannheim GmbH. The analytical performance was shown to be excellent. The clinical data from 2,037 patients demonstrate that for non-small-cell lung carcinoma CYFRA 21-1 has a higher diagnostic sensitivity compared to the established markers. Mainly for squamous cell carcinoma CYFRA 21-1 was superior (60%) to CEA (18%) or SCC (31%).

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Lung Neoplasms; Male; Ovarian Neoplasms; Peptide Fragments; Sensitivity and Specificity; Stomach Neoplasms

Cytokeratin-type intermediate filaments are a polygenic family of insoluble proteins that vary according to cell of origin and have been proposed as potentially useful markers of differentiation in epithelial malignancies. Because gastrointestinal malignancies resemble each other in their expression of many soluble antigens, we compared the cytokeratins of seven colonic, three gastric, six pancreatic, and one duodenal carcinoma cell lines, and one colon villous adenoma cell line. Cytokeratins were characterized by one- and two-dimensional gel electrophoresis, immunoblotting, and immunocytochemistry. These cell lines expressed combinations of cytokeratins 7, 8, 18, and 19, which are typical of the "simple" epithelial pattern found in normal ductal and glandular tissues of the gastrointestinal tract. However, pancreatic carcinoma cell lines expressed additional cytokeratins that are normally found in stratified squamous epithelium and epidermoid (squamous cell) carcinomas. These additional cytokeratins consisted of cytokeratin 16 in all six cell lines and cytokeratins 4, 13, and 16 in one cell line. These results suggest that cytokeratin patterns represent stable markers that may aid in distinguishing gastrointestinal malignancies.

Topics: Adenocarcinoma; Animals; Cell Line; Colonic Neoplasms; Diagnosis, Differential; Humans; Keratins; Mice; Pancreatic Neoplasms; Stomach Neoplasms; Tumor Cells, Cultured

In the present study we investigated the cytokeratin (CK) polypeptide expression in gastric and colonic adenocarcinomas. A battery of monoclonal anti-cytokeratin-specific antibodies and anti-vimentin were used. While the majority of cases displayed simple epithelial characteristics, in three of 17 cases of gastric adenocarcinomas and in one of 20 cases of colonic adenocarcinomas, CK polypeptides 13 (54 kd) and 16 (48 kd) were occasionally detected. These CK polypeptides, characteristic of squamous nonkeratinizing epithelia, were found in cases in which no evidence of squamous differentiation could be demonstrated by histologic examination. We believe that the presence of these unique CK polypeptides points to the squamous differentiation potential of the tumor cells.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Colonic Neoplasms; Fluorescent Antibody Technique; Humans; Keratins; Peptides; Stomach Neoplasms

Cell kinetics of reversible and persistent forestomach lesions induced by the genotoxic agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and/or the nongenotoxic antioxidant butylated hydroxyanisole (BHA) was investigated. A total of 184 male F344 rats were divided into four groups: Group 1 given an initial single gastric intubation of MNNG received 2% BHA diet from the third wk to the 26th wk and then basal diet; Group 2 receiving 2% BHA without MNNG initiation; Group 3 given MNNG alone; and Group 4 serving as a nontreated control. Rats were sequentially sacrificed at 6, 16, 26, 30, and 46 wk. Bromodeoxyuridine was administered either as a single i.p. injection (100 mg/kg of body weight) 1 h before killing or continuously via an osmotic minipump (120 micrograms/h) for 1, 3, or 7 days prior to sacrifice, in each case labeled cells being detected by immunohistochemistry. Squamous cell hyperplasia (SCH) and basal cell hyperplasia (BCH), each characterized by different phenotypic keratin expression, were induced in Groups 1 to 3. After withdrawal of BHA, rapid regression of SCH and extremely slow regression of BCH were observed. Papillomas and squamous cell carcinomas developed irreversibly in Group 1 and 3, BHA significantly (P less than 0.01) enhancing the incidence of SCC in Group 1. Flash and continuous bromodeoxyuridine labeling revealed SCH to consist of cells of high mitotic activity and short life span, whereas BCH consisted of cells with low mitotic activity and long life span. In addition, highly labeled areas were observed in SCH after cessation of BHA feeding in Group 1 without regression, and similar lesions were also evident in Group 3. The results suggest that rapid regression of SCH and slow regression of BCH reflect different cell kinetic patterns and that highly labeled areas after release from stimulating agents might be preneoplastic changes related to cancer development.

Topics: Animals; Butylated Hydroxyanisole; DNA; Epithelium; Hyperplasia; Immunoenzyme Techniques; Keratins; Male; Methylnitronitrosoguanidine; Precancerous Conditions; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms; Time Factors

A total of 113 patients with carcinomas of breast, testis, stomach and colon were examined for lymph node metastases by means of an exact case-by-case comparison by conventional histology and by immunohistochemistry using the anticytokeratin monoclonal antibody A45-B/B3. Among 891 examined lymph nodes, 90% of metastases were recognized by both methods, about 2% by histology alone, and more than 10% by immunohistochemistry alone. The method can be applied for intraoperative frozen section diagnosis.

Topics: Breast Neoplasms; Colonic Neoplasms; Female; Frozen Sections; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Paraffin; Stomach Neoplasms; Testicular Neoplasms

Of 17 cases of small cell carcinoma of the stomach, three were early and 14 were advanced. Grossly, the tumors were mostly polypoid at the early stage, and as they advanced, deep ulcerations developed. Histologically, only one tumor was "oat cell type," and the other 16 were "intermediate cell type." With regard to tumor components, five were "pure" tumor, and 12 were "composite" admixing glandular and/or squamous differentiation. Argyrophil cells were seen in eight tumors. Immunohistochemically positive cells for chromogranin, neuron-specific enolase, and keratin were seen in 12, 10, and 7 tumors, respectively. Carcinoembryonic antigen was negative in the small cell component of most tumors as opposed to strong positivity in the glandular component. Electron-dense core granules were evident in seven of nine tumors examined. These findings suggest that histologic variety is quite characteristic of the small cell carcinomas of the stomach, and this type of carcinoma takes an aggressive clinical course like its counterparts in other organs.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Small Cell; Chromogranins; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Stomach Neoplasms; Survival Analysis

Monoclonal antibodies (Mab) are potent probes to identify individual tumour cells or small tumour cell clusters in bone marrow. In the present study, various antibodies directed against either cell surface or intracytoplasmic antigens of epithelial cells were assessed for their ability to detect such cells in bone marrow of patients with breast, colorectal and gastric cancer. According to the presented data, monoclonal antibodies against intracellular cytokeratin (CK) components are superior in terms of specificity and sensitivity to antibodies reacting with epitopes of the cell membrane. Using a monoclonal antibody against the cytokeratin polypeptide 18 in connection with the alkaline phosphatase anti-alkaline phosphatase detection system (APAAP), we could detect tumour cells in bone marrow of 34 out of 97 patients with gastric cancer examined at the time of primary surgery. The incidence of positive findings was correlated to established risk factors, such as histological classification and locoregional lymph node involvement. Clinical follow-up studies on 38 patients demonstrated a significantly increased relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Thus the described technique may help to identify patients with gastric cancer carrying a high risk of early relapse.

Topics: Antibodies, Monoclonal; Antigens, Surface; Bone Neoplasms; Breast Neoplasms; Colorectal Neoplasms; Female; Humans; Keratins; Stomach Neoplasms

Seventeen gastric carcinomas (intestinal n = 12; diffuse n = 1; mixed type n = 4) and one Barrett's carcinoma were prospectively studied by immunohistochemistry for the expression of different keratin polypeptides and of the brush border markers villin, sucrase isomaltase and aminopeptidase N. All carcinomas expressed the keratin polypeptides 8, 18, and 19 and were stained by the broad specific keratin antibody KL1, irrespective of histologic type. Keratin 7, however, was expressed in only one carcinoma in most tumor cells and in two further carcinomas in some tumor cells. Thus, specific differentiation of the various histologic types of gastric carcinoma does not seem to be aided by the use of keratin antibodies. Villin was positive in 80% of the tumors and sucrase isomaltase and aminopeptidase N were positive in 67% respectively with no obvious histologic difference. The frequent positivity of the brush border markers, usually typical for intestinal epithelium, reflects the high degree of intestinal differentiation of gastric carcinomas, but again does not seem to be associated with a particular histologic type.

Topics: Adenocarcinoma; Adult; Aged; Aminopeptidases; Biomarkers, Tumor; Carrier Proteins; CD13 Antigens; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Gastrectomy; Humans; Intestinal Mucosa; Keratins; Male; Microfilament Proteins; Middle Aged; Peptides; Stomach Neoplasms; Sucrase-Isomaltase Complex

For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.

Topics: Adenocarcinoma, Mucinous; Antibodies, Monoclonal; Antigens, Neoplasm; Blotting, Western; Cell Line; Electrophoresis, Gel, Two-Dimensional; Fluorescent Antibody Technique; Humans; Immunoassay; Immunoenzyme Techniques; Keratins; Molecular Weight; Neoplasm Proteins; Reference Values; Stomach Neoplasms

A case of primary gastric plasmacytoma expressing various surface and cytoplasmic antigens is reported. With the use of formalin-fixed and deparaffinized sections, 13 different antibodies were applied. Neoplastic plasma cells revealed monoclonal IgG and kappa light chain in the cytoplasm, and expressed epithelial membrane antigen, Ki 67 antigen, cytokeratin, CD 22 antigen, interleukin-2 receptor antigen, leukocyte common antigen and Ki-1 (CD 30) antigen. However, tumor cells were devoid of HLA-DR antigen. These data suggest that the neoplastic plasma cells are at the plasmoblastic stage of maturation and express various surface and cytoplasmic phenotypes.

Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, B-Lymphocyte; Antigens, Neoplasm; Antigens, Surface; Cell Adhesion Molecules; Female; Humans; Immunohistochemistry; Keratins; Ki-1 Antigen; Ki-67 Antigen; Lectins; Leukocyte Common Antigens; Membrane Glycoproteins; Mucin-1; Plasmacytoma; Receptors, Interleukin-2; Sialic Acid Binding Ig-like Lectin 2; Stomach Neoplasms

A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.

Topics: Antigens, Differentiation; Biomarkers, Tumor; Carcinoma; Diagnostic Errors; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Lymphoma; Middle Aged; Stomach Neoplasms

By co-culturing regional lymph node B-cells and HAT-sensitive mutant cells obtained from RPMI-1788 cells, no less than 20,000 Epstein-Barr (EB)-transformed colonies were obtained from 32 patients with gastric cancer. From B-cell cultures generating antibodies reactive with gastric cancer tissues as well as cultured gastric cancer cells, two EB-transformed cell clones termed C418-59 and C1218-39 were isolated. Both of them produced human IgM-class antibodies, termed Mab418-59 and Mab1218-39, respectively. Both antibodies reacted with an antigen with a molecular weight of 45 kd existing in gastric cancer MKN-45, MKN-1, and Kato-III cells, and also with all of 4 adenocarcinomas of the stomach in paraffin sections. The antigen recognized by both antibodies was identified as a kind of cytoskeletal protein, cytokeratin 18. In this study, it was confirmed that B-cell clones generating autoantibodies against cytokeratin 18 were present in some patients with gastric cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Autoantibodies; B-Lymphocytes; Blotting, Western; Cell Transformation, Viral; Electrophoresis, Polyacrylamide Gel; Herpesvirus 4, Human; Humans; Immunoenzyme Techniques; Immunoglobulin M; Keratins; Lymph Nodes; Molecular Weight; Stomach Neoplasms; Tumor Cells, Cultured

Immunohistochemical studies on synovial sarcomas have proved the potentiality of these neoplasm for epithelial and mesenchymal differentiation and antibodies detecting epithelial cells have been found to be helpful in determining the histological types. In this study different epithelial markers directed against various cytokeratins, HMFG-2 and EMA were investigated on paraffin embedded tissues of 13 cases of synovial sarcomas, with regard to their reliability in unmasking the epithelial components demonstrable in this type of neoplasm. The results lead to three conclusions: firstly, synovial sarcomas possess the capacity for generating different epithelial cell types with uncommon compositions of intermediate filaments as well as of membrane proteins, secondly, these features may be expressed in a heterogenous pattern even within the same tumour and finally, the use of wide range anti-cytokeratin antibodies covering the spectrum of basic as well as acidic type proteins seems to be necessary for the detection of all epithelial components demonstrable in synovial sarcomas.

Topics: Antibodies; Biomarkers, Tumor; Breast Neoplasms; Epithelium; Gallbladder Neoplasms; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Sarcoma, Synovial; Skin Neoplasms; Stomach Neoplasms; Synovial Membrane

Topics: Actins; Adolescent; Adult; Aged; Antibodies, Monoclonal; Biomarkers, Tumor; Desmin; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Myelin Basic Protein; S100 Proteins; Stomach; Stomach Neoplasms; Vimentin

Occurrence and expression of cytokeratins were studied by the immunoperoxidase-antiperoxidase (PAP) technique in formalin-fixed, paraffin embedded material from 18 cases of carcinoid tumours of the gastrointestinal tract. Polyclonal antikeratin for wide spectrum screening was detected in 12 cases; low molecular weight cytokeratins, C19 and CAM5.2 were positive in majority of the cases whereas antikeratins for high molecular weight were negative in all. Similar positive immuno-reactivity with antibodies to cytokeratins were detected in the surrounding epithelial cells. These results suggest that carcinoids of the gastrointestinal tract originate from the endodermal stem cell and differentiates along one or more directions, and the immunohistochemical findings depend upon the direction of their differentiation.

Topics: Appendiceal Neoplasms; Biomarkers, Tumor; Carcinoid Tumor; Gastrointestinal Neoplasms; Humans; Ileal Neoplasms; Immunoenzyme Techniques; Keratins; Rectal Neoplasms; Retrospective Studies; Stomach Neoplasms

We report a case of gastric carcinoma with an unusual histologic appearance and type of cellular differentiation. The tumor was resected from an 85-yr-old man who presented with epigastric pain and monoclonal gammopathy. The tumor was antral in location and transmurally infiltrated the stomach wall. Histologically, the tumor closely resembled a lymphoma with diffuse poorly cohesive sheets of tumor cells interspersed with histiocytes. Immunohistochemical study, however, clearly demonstrated the epithelial nature of this tumor. Electron microscopy also revealed evidence of epithelial differentiation and features of parietal cell differentiation. In this report, we describe the light and electron microscopic findings, immunohistochemical staining properties, and DNA flow cytometric findings of this tumor and briefly review the literature on parietal cell carcinomas.

Topics: Aged; Aged, 80 and over; Carcinoma; Diagnosis, Differential; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Parietal Cells, Gastric; Stomach Neoplasms

Topics: Antigens, Differentiation; Diagnosis, Differential; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Lymphoma; Stomach Neoplasms

Topics: Antigens, Differentiation; Gene Expression; Histocompatibility Antigens; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Stomach Neoplasms

A composite tumor of the gastric antrum composed of areas of adenocarcinoma and poorly differentiated carcinoid is described, with histochemical and immunohistochemical documentation of endocrine and nonendocrine differentiation. The neoplasm maintained a composite architecture both within the site of origin and in lymph node metastases. The adenocarcinoma displayed a predominantly tubular architecture with focal sheets of clear cells. The poorly differentiated carcinoid was argyrophilic, chromogranin immunoreactive, and focally serotonin immunoreactive, and contained keratin intermediate filaments in a distinctive distribution suggestive of endocrine differentiation. Among the tumors of the carcinoma-carcinoid spectrum, the composite tumor is less common than either carcinomas with interspersed endocrine cells or carcinoids with interspersed nonendocrine cells.

Topics: Adenocarcinoma; Carcinoid Tumor; Chromogranins; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Male; Middle Aged; Stomach Neoplasms

Gastric carcinomas have been assayed for the presence of villin and for the small intestinal hydrolases aminopeptidase N and sucrase isomaltase. These proteins seem not to be present in normal stomach epithelium. However intestinal metaplasia in stomach, and tumour cells in the glandular patterns of gastric carcinoma were positive for all three markers, showing characteristic apical positivity. In contrast, in diffuse gastric carcinomas the percentage of signet ring cells positive for these markers varied from 10-100% with each marker showing a similar percentage of positive cells. Testing of gastric carcinomas with antibodies specific for different keratin polypeptides showed that while all 7 tumours were positive for keratins 8 and 18.2 were also positive for keratin 7. In the keratin 7 positive tumours all tumour cells were keratin 7 positive. The keratin 8 antibody also reacted on routinely fixed specimens. Thus gastric carcinomas reveal different degrees of gastric and intestinal differentiation.

Topics: Adenocarcinoma, Mucinous; Alkaline Phosphatase; Aminopeptidases; Calcium-Binding Proteins; Carrier Proteins; CD13 Antigens; Fluorescent Antibody Technique; Frozen Sections; Humans; Hydrolases; Immunohistochemistry; Intestine, Small; Keratins; Metaplasia; Microfilament Proteins; Microvilli; Stomach Neoplasms; Sucrase-Isomaltase Complex

Definitive diagnosis of gastric large cell lymphoma and its distinction from anaplastic carcinoma in endoscopic biopsy material may be problematic. To assess the utility of immunohistochemical studies in routinely processed, paraffin-embedded tissue in this situation, we applied immunostaining for leukocyte common antigen (LCA) and cytokeratin in 17 cases diagnosed on biopsy as undifferentiated malignant tumor but proved on resection to be primary gastric large cell lymphoma. Clinical and endoscopic features failed to distinguish lymphoma from carcinoma in these cases. Immunoreactivity for LCA occurred in 15 cases (88 per cent) and was correctly and readily interpreted on blinded evaluation. Open review increased the yield to 16 cases (94 per cent). Tumor cells were uniformly negative for cytokeratin; however, staining of adjacent epithelium for cytokeratin provided additional confirmation of the lymphoid nature of the tumor. The one case in which excessive background staining precluded interpretation consisted of a single biopsy specimen of necrotic tumor. We conclude that antibodies to LCA and cytokeratin are sensitive, specific, and reliable diagnostic adjuncts that are useful in the definitive biopsy diagnosis of gastric large cell lymphoma.

Topics: Adolescent; Adult; Aged; Antibodies; Biopsy; Histocompatibility Antigens; Histocytochemistry; Humans; Immunochemistry; Keratins; Leukocyte Common Antigens; Lymphoma; Middle Aged; Stomach Neoplasms

Immunoperoxidase staining for human keratin proteins was performed cytologically on samples from 90 patients with malignant tumors, and histologically on samples from 164 patients with malignant tumors. At the cytological level, almost all tumor cells not only in squamous cell carcinoma but also in nonsquamous cell carcinoma were positive for keratin proteins, in contrast with the apparent abscence of keratin proteins in sarcoma. At the histological level, almost all neoplastic cells of squamous cell carcinoma were positive for keratin proteins, the same as at the cytological level. In contrast, among cases of nonsquamous cell carcinoma, the frequency of appearance of keratin proteins varied according to the organ; it tended to be low in tumors with relatively good prognosis, such as carcinomas in the digestive system or thyroid cancer, and to be high in tumor with poor prognosis, such as pulmonary cancer, gallbladder cancer and endometrial cancer. However, there was a marked difference between the frequency of appearance of keratin proteins at the cytological level and that at the histological level, particularly in the cases of gastric cancer.

Topics: Antibodies; Breast Neoplasms; Colonic Neoplasms; Female; Gallbladder Neoplasms; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Neoplasms; Sarcoma; Stomach Neoplasms; Thyroid Neoplasms; Uterine Neoplasms

Topics: Animals; Carcinoma, Squamous Cell; Female; Horse Diseases; Horses; Keratins; Myiasis; Neoplasm Metastasis; Stomach; Stomach Diseases; Stomach Neoplasms

Topics: Animals; Dimethylnitrosamine; Epidermis; Keratins; Male; Microscopy, Electron, Scanning; Papilloma; Rats; Stomach Neoplasms; Zinc

Immunoperoxidase staining for human keratin proteins (hKP) was performed cytochemically in samples from 79 cancer patients, and histochemically in samples from 134 cancer patients. Immunohistochemically, hKP was present in almost all patients with squamous cell carcinoma (lung), transitional cell carcinoma (urinary bladder), adenocarcinoma (lung, stomach, breast, ovary), bronchiole-alveolar carcinoma (lung), and large cell carcinoma (lung). It was detected in 40% of the patients with small cell carcinoma (lung). Histochemically, hKP was present in patients with squamous cell carcinoma (lung, uterine body), adenocarcinoma (lung, stomach, colon, gall bladder, thyroid, uterine body), adenosquamous cell carcinoma (gall bladder, uterine body), Signet-ring cell carcinoma (stomach), clear cell carcinoma (uterine body) and undifferentiated carcinoma (uterine body). However, it was not detected in patients with brochiole ++-alveola ++ carcinoma (lung) and mucinous carcinoma (gall bladder).

Topics: Breast Neoplasms; Colonic Neoplasms; Female; Histocytochemistry; Humans; Keratins; Lung Neoplasms; Male; Neoplasms; Stomach Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms

Determination of the type of intermediate filaments (IFs) present in a cell or tissue can yield information about its origin. Thus cells can be grouped into six different classes, i.e. epithelial cells characterized by cytokeratins, most but not all neurones characterized by neurofilaments (NFs), glial cells characterized by the presence of glial fibrillary acidic filaments, muscle cells characterized by the presence of desmin filaments, mesenchymal cells and certain other nonepithelial cell types characterized by the presence of vimentin, and other cells that appear not to contain IFs. The assignments made by immunologic techniques are supported by protein chemistry of the isolated proteins. Information derived from protein sequences as well as from DNA sequences establish that the major intermediate-filament proteins are different but related molecules and show also that the alpha-keratins of wool belong to this multigene family. Applications of IF typing to human pathologic material, and especially to the different major subgroups of human tumors, are reviewed. Thus, for instance, carcinomas continue to express cytokeratins, many tumors of neuronal origin express NFs, gliomas express glial fibrillary acidic protein (GFA), rhabdomyosarcomas express desmin, and nonmuscle sarcomas express vimentin. Further subclassification of epithelial cells and carcinomas is discussed. The subdivisions obtained by IF typing are striking because they follow well-known histologic principles; thus IF typing seems useful in certain instances where diagnosis is difficult by conventional techniques.

Topics: Animals; Cytoskeleton; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Melanoma; Skin; Stomach Neoplasms; Vimentin

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