bromochloroacetic-acid and Rectal-Neoplasms

A 60-years old male was admitted to our department for investigation of constipation and hypogastric discomfort intensified during defecation of a few weeks duration. The cause proved to be a rectal carcinosarcoma that was treated by abdominoperineal resection and postoperative chemo-radiotherapy. The patient died 6 months later due to hepatic failure, showing evidence of disseminated disease. In general colonic carcinosarcomas constitute a rare category of malignant neoplasms whose nature is still incompletely understood. No specific treatment guidelines exist. Surgery is the mainstay of treatment and regardless of the addition of adjuvant therapy the prognosis is very poor. Systematic genetic analysis may be the clue for understanding the pathogenesis of these mysterious tumors.

Topics: Biomarkers; Carcinosarcoma; Combined Modality Therapy; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Rectal Neoplasms; Tumor Suppressor Protein p53

We report a case of adenocarcinoma of the rectum with foci of metaplastic shadow cells. The patient was a 65 year old man with anemia. Macroscopically the tumor was an ordinary rectal cancer. Microscopically, in addition to the features of moderately differentiated adenocarcinoma invading the subserosa, islands of shadow cells in tumor nests were detected in both primary and one of three pericolic metastatic lymph node lesions. Neoplastic glandular cells showed gradual transition to shadow cells. An antibody specific for high-molecular-weight cytokeratins reacted with the shadow cells and intermediate zone epithelial cells surrounding them, but no CEA, low-molecular-weight cytokeratins or cyclin D1 was detectable in them. Cytokeratin 14 was expressed only in the transitional zone epithelial cells. The intermediate zone epithelial cells were regarded as metaplastic squamous cells, from which the shadow cells were derived. The patient died of multiple liver metastases nine and a half months after surgery. To our knowledge, this is the first report of an immunohistochemical study of rectal adenocarcinoma containing shadow cells not only in the primary lesion but also in a metastatic lymph node.

Topics: Adenocarcinoma; Aged; Carcinoembryonic Antigen; Cyclin D1; Epithelial Cells; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Metaplasia; Rectal Neoplasms; Rectum; Tumor Suppressor Protein p53

The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance.. Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival.. The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P<0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P=0.002).. This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.

Topics: Aged; Colectomy; Colonic Neoplasms; Coloring Agents; Disease-Free Survival; Female; Fluorescent Dyes; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prospective Studies; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Rosaniline Dyes; Sentinel Lymph Node Biopsy; Survival Rate

Recent surgical concepts for primary rectal cancer include the combination of surgery and short-term neoadjuvant radiotherapy (STNR). This is usually given in a dose of 25 Gy over five days in order to reduce local recurrence rates. Clinical studies have shown that local recurrence is found in some patients despite STNR. We identified molecular patterns of the Wnt- and apoptosis pathways as well as expression of junction-associated molecules in rectal cancer specimens of patients who received STNR and in those who did not. Expression patterns were examined by immunohistochemistry and molecular techniques such as LightCycler RT-PCR and Western blot analysis in 25 sporadic rectal adenocarcinoma specimens derived from STNR-patients or non-pretreated donors, respectively. The molecular pattern in response to STNR was heterogeneous and was reflected by responders who show activation of apoptosis and cellular remodeling, whereas the group of non-responders from STNR did not show such reaction and was very similar to untreated controls. Enhanced expression of beta-catenin was generally mediated by STNR, but exclusively in the responder group impaired expression of c-Myc and junction-associated molecules as well as cleavage of poly-ADP-ribose polymerase and of the caspase substrate cytokeratin 19 were found. The molecular profile suggests that STNR interferes with Wnt-signaling and c-Myc expression. STNR in its present form is not suitable to fully complete the sequence of apoptosis in all rectal adenocarcinomas.

Topics: Adenocarcinoma; Adult; Aged; Apoptosis; beta Catenin; Blotting, Western; Cytoskeletal Proteins; Dose Fractionation, Radiation; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Keratins; Male; Middle Aged; Neoadjuvant Therapy; Proto-Oncogene Proteins c-myc; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Trans-Activators; Wnt Proteins

Using digital scans of all tumour slides/case, we analysed CD8. In rectal cancer, tumour budding has clinical relevance in both primarily surgically treated patients and in those with neoadjuvantly treated patients, where it characterises highly aggressive residual disease. CD8

Topics: CD8 Antigens; CD8-Positive T-Lymphocytes; Colonic Neoplasms; Drug Therapy; Female; Humans; Immunohistochemistry; Keratins; Male; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Rectal Neoplasms

Rectal squamous cell carcinoma (SCC) is a rare tumor with unresolved etiology. Human immunodeficiency virus-infected individuals and solid organ transplant recipients experience >30-fold and approximately 3-fold elevated rates of rectal SCC, respectively, suggesting immunosuppression plays a role.

Topics: Adenocarcinoma; Anus Neoplasms; Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; DNA-Binding Proteins; DNA, Viral; Human papillomavirus 16; Humans; In Situ Hybridization; Keratins; Oncogene Proteins, Viral; Papillomavirus Infections; Rectal Neoplasms; Repressor Proteins; Transcription Factors; Tumor Suppressor Proteins; Viral Envelope Proteins

Müllerianosis is the term used to designate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic location. In this report, we describe a case of incidental vaginal müllerianosis in a 59-year-old woman who underwent rectosigmoidectomy for rectal adenocarcinoma. In the vaginal cuff removed for neoplastic invasion, a separate multilocular mass measuring 1.5cm was found. The microscopic examination of the vaginal wall revealed endosalpingeal, endocervical and endometrial dilated or cystic glands with predominance of the endosalpingeal epithelium. Müllerian epithelium showed positivity for cytokeratins 7 and 8/18, high molecular weight cytokeratin, estrogen receptor alpha, and androgen receptor. The periglandular stroma was condensed and reactive for smooth-muscle actin, h-caldesmon, and CD10. To the best of our knowledge, a case of vaginal müllerianosis has not been previously reported. This lesion should be differentiated form vaginal adenosis and primary well-differentiated vaginal adenocarcinoma. The vagina should be added to the list of locations in which müllerianosis can be observed.

Topics: Adenocarcinoma; Cervix Uteri; Choristoma; Endometrium; Fallopian Tubes; Female; Humans; Incidental Findings; Keratins; Middle Aged; Rectal Neoplasms; Vaginal Diseases

Although several studies have shown that the presence of acellular mucin pools in surgical specimens with rectal carcinomas examined after preoperative chemoradiotherapy indicated complete response to therapy, the proper meaning of these pools has yet to be elucidated. The aims of this study were to analyze the immunoprofile of acellular mucin pools and to review the relevant literature.. In 30 consecutive rectal cancers that were preoperatively treated with chemoradiotherapy, the clinicopathologic features were correlated with the immunoexpression of AE1/AE3 keratin and carcinoembryonic antigen (CEA).. Acellular mucin pools were present in all the cases, independently by their preoperative histological aspect. In remnant tumors (n=20), they were present at the invasion front and were marked by CEA. In cases without remnant tumor cells (n=10), they also displayed CEA positivity. In 2 of the 10 cases, isolated tumor cells were identified after multilevel sectioning of paraffin-embedded blocks.. The presence of acellular mucin pools in surgical specimens of rectal cancers cannot be interpreted as an indicator of complete response to radiotherapy if at least 10 multilevel sections are performed in at least three tumor blocks per case, and CEA negativity is not proved.

Topics: Aged; Carcinoembryonic Antigen; Carcinoma; Chemoradiotherapy; Female; Humans; Keratins; Male; Middle Aged; Mucins; Preoperative Period; Rectal Neoplasms

Although guidelines recommend a 2 cm distal margin in sphincter-saving operations for rectal cancer, some studies have shown that it may be decreased to 1cm after preoperative radiotherapy. At the present time, there are no established guidelines that suggest a specific distal safety margin for rectal cancer after preoperative radiotherapy. This study aims to examine whether preoperative radio therapy can reduce the distal safety margin in the treatment of lower rectal cancers.. We examined the distal spread by H&E and immunohistochemical staining of CAM5.2 (epithelial marker) in serial sections of surgically resected specimens. To evaluate the extent of distal intramural spread, we defined the "DS length" as the distance between the microscopically defined distal tumor border and the distal spread. We compared the DS length between 20 patients who underwent preoperative radiotherapy followed by surgery (Rad (+) group) and 20 surgery-alone (Rad (-)group).. The average DS length was significantly smaller in the Rad (+) group (3.2mm) than in the Rad (-) group (6.3mm) (p=0.028). Furthermore,the greatest DS length was 5.8mm in the Rad (+) group,but 11.5mm in the Rad (-) group. No patient showed a DS length of over 1cm in the Rad (+) group.. These results suggested that the safety margin may be reduced to 1cm by preoperative radiotherapy.Therefore, preoperative radiotherapy may extend the indications for sphincter-saving operation.

Topics: Aged; Biomarkers; Combined Modality Therapy; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Rectal Neoplasms

Predictive tools for local recurrence (LR) of rectal cancer are needed. This study assessed the predictive value of tumour budding detected by MNF-116 and laminin-5 γ2 chain (Ln-5 γ2).. In a case-control study, the surgical specimens of 48 patients with LR after from primary resection of rectal carcinoma and 82 control patients matched for gender and preoperative radiation from a population of 1180 patients operated with total mesorectal excision were studied. The presence of budding was examined using immunohistochemistry with Ln-5 γ2 and pan-cytokeratin staining with MNF-116.. Tumour budding counts ranged from 0 to 106 buds (mean 43, median 38) for all patients. Significantly more tumours with more than 35 buds were seen in the LR than in the control group (67 vs 44%; P = 0.02). The spread of budding was also more extensive in the LR than in the control group (63 vs 49%, P = 0.03). In a multivariate analysis with tumour, node, metastasis stage, MNF-116-stained budding was an independent predictor of local failure (P = 0.02). The budding frequency was higher in irradiated tumours in comparison with tumours that had not received irradiation (mean 53 vs 38, P = 0.03). For Ln-5 γ2, more tumours with ≥ 10 buds were seen in the group with LR than among the control patients, but this difference was not statistically significant (73 vs 57%; P = 0.09). No additive value was found in the multivariate logistic regression model when Ln-5 γ2-stained budding frequency was added to MNF-116 and tumour, node, metastasis stage. The agreement between budding frequency determined by MNF-116 and Ln-5 γ2 was moderate, with a κ-coefficient of 0.34 (0.16-0.51).. Tumour budding determined by MNF-116 staining may serve as a predictive marker for LR in rectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Case-Control Studies; Female; Humans; Immunohistochemistry; Keratins; Laminin; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Predictive Value of Tests; Rectal Neoplasms; Staining and Labeling

Pathologic complete remission (CR) of rectal cancer after neoadjuvant chemoradiation therapy (CRT) is generally confirmed by routine hematoxylin and eosin (H&E) staining. The aim of this study was to identify residual rectal cancer cells in primary lesions of patients with pathologic CR by immunohistochemical staining for cytokeratin.. The medical records of 358 rectal cancer patients who underwent neoadjuvant CRT prior to radical surgery between October 2002 and August 2007 were reviewed. The authors stained sections of resected specimens of 58 patients (15.9%; 42 males; mean age 54 years) who achieved pathologic CR (as determined originally by H&E staining) with H&E and performed immunohistochemistry (IHC) using monoclonal anti-cytokeratin antibody. These stained sections were reviewed for residual rectal cancer cells by a pathologist.. Of the 58 patients that achieved CR by initial pathologic examinations, eight (13.8%) were found to contain tumor by cytokeratin IHC. H&E staining revealed that six of these were positive for cancer cells, but the remaining two were negative for residual rectal cancer cells.. Through better identification of residual rectal cancer cells, cytokeratin IHC offers a means of improving staging accuracy and thus provides useful information for prognosis and treatment decisions for patients with rectal cancer who had a clinical CR after CRT.

Topics: Demography; Female; Humans; Keratins; Male; Middle Aged; Neoplasm, Residual; Rectal Neoplasms; Remission Induction; Staining and Labeling

Previous studies revealed that the incidence of cancer cell involvement along the pelvic autonomic nerves ranged from 4 to 14%. However, patients' profiles and methodologies differed among the studies. This study was conducted to clarify the incidence of cancer cell involvement in and around the pelvic autonomic nerves immunohistochemically.. Immunohistochemical staining was performed on pelvic autonomic nerve specimens resected from 17 patients with p-Stage I-III lower rectal cancers. Antibodies used were pan-cytokeratin (AE1/AE3) for staining cancer cells, S-100 for autonomic nerves, and D2-40 for lymphatic vessels. Lymphatic permeation around the pelvic autonomic nerves was defined as present when AE1/AE3-positive cells were detected in D2-40-stained lymphatic vessels. The presence of metastasis to the interstitial tissue or contaminants was also recorded.. TNM staging was stage I in 1, stage II in 5, and stage III in 11 cases, respectively. No cases had lymphatic permeation or metastasis to the interstitial tissue in and around the pelvic autonomic nerves. Cancer cell contaminants were seen in four cases (23%). In three cases (18%), metastatic nodes were located at the root of the middle rectal artery, very close to the pelvic autonomic nerves.. Cancer cell involvement was not seen in and around the pelvic autonomic nerves, suggesting that complete pelvic autonomic nerve preservation may be feasible, unless nerves are invaded by the tumor. In some cases, however, metastatic nodes were seen very close to the nerves. Meticulous lymph node dissection along the pelvic autonomic nerves is mandatory.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autonomic Pathways; Clinical Trials, Phase III as Topic; Female; Humans; Immunohistochemistry; Japan; Keratins; Lymph Node Excision; Lymphatic Metastasis; Lymphatic Vessels; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pelvis; Rectal Neoplasms; S100 Proteins; Treatment Outcome

Topics: Humans; Immunohistochemistry; Keratins; Prognosis; Rectal Neoplasms; Remission Induction

Topics: Adult; Diagnosis, Differential; Female; Humans; Keratins; Lymphatic Metastasis; Mucin-1; Rectal Neoplasms; Rhabdoid Tumor; Sarcoma; Synaptophysin; Vimentin; Young Adult

The aim of this study was to determine the incidence of isolated tumor cells (ITC) and micrometastasis in lateral lymph nodes of patients with rectal cancer and its possible correlation with prognosis.. One hundred seventy-seven rectal cancer patients who underwent curative resection with lateral lymph node dissection were enrolled. Dissected lymph nodes were examined using hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) with anti-keratin antibody (AE1/AE3). States of lymph node metastasis were divisible into three groups: detectable with HE (HE+), detectable with only IHC (HE-/IHC+), and undetectable even with IHC (IHC-). Almost all the HE-/IHC+ group was classified as ITC consisting of a few tumor cells according to the UICC criteria (ITC+). Survival rates were compared among HE+, ITC+, and IHC-.. ITC+ were detected in 24.1% of patients with HE-negative lateral lymph nodes. No significant difference in overall 5-year survival was observed between ITC+ and IHC- patients (76.1 and 82.9%, respectively, p = 0.25). Multivariate analysis showed that perirectal HE+ lymph nodes, but not ITC+ lateral lymph nodes, was an independent prognostic factor.. ITC in lateral lymph nodes does not contribute to the prognosis of rectal cancer in patients who undergo extended lateral lymph node dissection, unlike HE+ lateral lymph node metastasis.

Topics: Adult; Aged; Digestive System Surgical Procedures; Eosine Yellowish-(YS); Female; Follow-Up Studies; Hematoxylin; Humans; Immunohistochemistry; Incidence; Kaplan-Meier Estimate; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Proportional Hazards Models; Rectal Neoplasms; Staining and Labeling; Treatment Outcome

We performed D2 low anterior resection in a patient with stage I rectal cancer [pathological diagnosis: proper muscle (pm) invasion, n0, lymphatic invasion (ly), (-); venous invasion (v), (-); anal margin, (-)]. The tumor recurred at the anastomotic site approximately one year later and was treated with Miles' operation [pm, n0, ly (+); v (-); deep border of the primary tumor (-)]. The tumor marker CEA increased to 50.4 ng/ml at four months after surgery and pelvic local recurrence was detected. Since then, the patient has been receiving chemoradiotherapy on an out-patient basis. Cytokeratin immunostaining of all the lymph nodes collected during the two operations showed clusters of occult neoplastic cells (ONCs) in the perinodal fat around the nodes harvested at the first operation. These findings suggest that the risk of local recurrence of rectal cancer is increased even in stage I disease if ONCs are found in the perinodal fat. Further studies are required to examine the relationship between local recurrence and extranodal ONCs in patients with primary rectal cancer.

Topics: Aged; Anastomosis, Surgical; Humans; Keratins; Male; Muscle, Skeletal; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Pelvis; Rectal Neoplasms; Treatment Outcome

This study was designed to evaluate one institution's experience with treatment outcomes for rectal squamous-cell carcinoma.. Using our prospective Colorectal Database, we identified patients diagnosed with rectal squamous-cell carcinoma at our institution between 1983 and 2005. Pathology was rereviewed, tumor immunophenotype was compared to control cases of anal squamous-cell carcinoma and rectal adenocarcinoma, treatment modalities and outcomes were analyzed.. Twelve patients were identified (10 females median age, 58 years). Median distal extent of tumors was 7 (range, 5-8) cm from the anal verge. Treatment included chemotherapy only (n = 1), chemoradiation only (n = 2), induction chemotherapy followed by chemoradiation and surgery (n = 2), chemoradiation followed by surgery (n = 5), and surgery followed by chemoradiation (n = 2). The chemotherapy regimen was 5-fluorouracil-based. Radiotherapy total dose was 50.4 Gy (1.8 Gy/day, daily x 5) external iliac and inguinal nodes were not included in the radiation field. Complete clinical responders to chemoradiation (n = 2) received no further treatment. All seven partial responders underwent surgery; six had complete pathologic response; nodal status in two of six was unknown because they had local excision. Immunophenotypical analysis showed similar keratin expression profile between rectal squamous-cell carcinoma (n = 5) and rectal adenocarcinoma (n = 5), which is different from anal squamous-cell carcinoma (n = 10). All patients were alive without evidence of disease at follow-up (median follow-up, 2.6 (range, 0.5-16) years).. Our data suggest that most patients treated with upfront chemoradiation therapy followed by surgery did well. Sphincter-preserving surgery is usually feasible. Clinical judgment of tumor response after chemoradiation is not completely reliable. Immunohistochemistry suggests a common cellular origin for rectal squamous-cell carcinoma and rectal adenocarcinoma, which is different from anal squamous-cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Colectomy; Female; Fluorouracil; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Radiotherapy, Adjuvant; Rectal Neoplasms; Survival Rate; Treatment Outcome; United States

We encountered a male patient aged 64 with pulmonary mucinous carcinoma in whom a diagnosis of pulmonary metastasis from early rectal cancer with submucosal invasion was made based on an immunohistochemical examination. A rectal cancer was detected together with a mass in the lung. The mass in the lung was consistent with mucinous adenocarcinoma, whereas the invasion of rectal cancer was confined to the submucosa; thus, distant metastases appeared unlikely. These lesions were assessed using immunohistochemical staining for cytokeratin and thyroid transcription factor-1, which failed to make a definite diagnosis. A further assessment was made by staining for villin. Both neoplasms were positive for this protein, demonstrating a common brush-border pattern. A lung metastasis from rectal cancer with submucosal invasion was diagnosed. Villin is considered useful for detecting primary neoplastic lesions based not only on its specificity but also on its staining pattern, which is different from that of other proteins.

Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Fatal Outcome; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Lung Neoplasms; Male; Microfilament Proteins; Middle Aged; Neoplasm Invasiveness; Nuclear Proteins; Rectal Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

This study was designed to examine whether disseminated tumor cells in peripheral blood of locally advanced rectal cancer patients undergoing preoperative chemoradiation have the potential to serve as a marker for therapy response. Studies suggest that patients with advanced rectal cancer who respond to preoperative chemoradiation most likely benefit from this treatment.. From advanced rectal cancer patients undergoing preoperative chemoradiation, peripheral blood was obtained at defined times: before, during, and after chemoradiation and during surgery. Patients were divided into histopathologic responders (ypT0-T2) and nonresponders (ypT3-T4). Cytokeratin 20 and carcinoembryonic antigen reverse transcriptase-polymerase chain reaction were performed to detect disseminated tumor cells. A blood sample was deemed positive for disseminated tumor cells if both carcinoembryonic antigen and cytokeratin 20 were detected.. The overall population (n = 26) showed a positivity rate of 32 percent for disseminated tumor cells before initiation of chemoradiation. Of the responders (n = 8), 63 percent were positive for disseminated tumor cells before chemoradiation, whereas only 18 percent of nonresponders (n = 18) were positive (P = 0.026). From initiation of chemoradiation to the end of surgery, a significant decrease was seen in tumor cell positivity in the blood of responders (P = 0.042). Moreover, the responders represented a trend toward a decrease in tumor cell positivity during chemoradiation (P = 0.079). In contrast, there were no noticeable alterations within the treatment course in nonresponders.. This prospective proof of principle study demonstrates that locally advanced rectal cancer with preoperative chemoradiation shows different biologic behavior in terms of tumor cell dissemination in peripheral blood when therapy responders compared with nonresponders.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoembryonic Antigen; Combined Modality Therapy; Feasibility Studies; Female; Humans; Keratins; Male; Middle Aged; Preoperative Care; Prospective Studies; Radiotherapy; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction

Intrabiliary growth of liver metastases from colorectal cancer has rarely been studied. A surgically resected case of a metastatic liver tumor with prominent intrabiliary growth derived from rectal cancer is reported. The patient was a 62-year-old man who had received a low anterior resection for rectal cancer in March 2000. He was re-admitted due to obstructive jaundice in January 2003, and was diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary tumor extending from the intrahepatic bile duct of segment II to the common hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI, and an extrahepatic bile duct resection with reconstruction of the biliary tract. In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in diameter in segments II and VI, respectively, and an intrabiliary tumor originating from the main tumor in segment II extended to the common hepatic duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to moderately differentiated adenocarcinoma, which showed the same histological features as the rectal cancer. The immunohistochemical findings strongly supported that these tumors, including the intrabiliary growth, were liver metastasis from the rectal cancer. The intrabiliary invasion and growth of metastatic liver tumors has generally been overlooked, notwithstanding their frequently observed biological behavior. The present case is informative, and further investigation into this type of metastatic liver tumor may be warranted.

Topics: Adenocarcinoma; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cholangiography; Cholestasis, Intrahepatic; Hepatectomy; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Rectal Neoplasms; Tomography, X-Ray Computed

The aims of this study were to determine the rate of lymph node micrometastases and to evaluate their prognostic value in lateral lymph nodes in lower rectal cancer at or below the peritoneal reflection.. A retrospective analysis was made of 892 lymph nodes from 66 consecutive patients who had undergone radical resection with lateral lymph node dissection. These lymph nodes were examined immunohistochemically with an antibody against cytokeratins 7 and 8, CAM5.2.. Routine hematoxylin-eosin staining revealed 9 patients with positive lateral lymph nodes that were stained consistently with CAM5.2. Among 57 patients in whom lateral lymph node metastases were not detected by hematoxylin-eosin staining, cytokeratin staining was positive in 19 nodes (2.7 percent) from 11 patients (19.3 percent). These 11 patients with micrometastases in lateral nodes showed a significantly high recurrence rate (P = 0.048) and worse overall survival (P = 0.01) than the 46 patients without lateral node metastases. The recurrence rate and overall survival of patients with micrometastases did not differ significantly from those of patients with positive lateral nodes with hematoxylin-eosin staining. Local recurrence developed in 6 of 66 patients, but neither the presence nor the absence of micrometastases in lateral nodes influenced the local recurrence rate.. The presence of nodal micrometastases leads to a poor prognosis. The survival of patients with micrometastases was not different from that of patients with overt metastases. Therefore, patients with cytokeratin-positive cells in lateral lymph nodes should be regarded as having overt metastases.

Topics: Abdominal Cavity; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Colectomy; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Rectal Neoplasms; Retrospective Studies; Survival Analysis

Colonic mucosa typically expresses cytokeratin (CK) 20 but not CK7. This CK20+/CK7- profile has been used to distinguish colonic adenocarcinoma from others arising in the lung, breast, or genitourinary tract. CK7 expression in colorectal adenocarcinoma has been reported to be rare, and when present, a metastatic origin needs to be excluded. However, we have observed a higher frequency of CK7 positivity in rectal adenocarcinomas. Paraffin sections of 42 rectal tumors (7 adenomas and 35 adenocarcinomas), 11 colonic adenocarcinomas proximal to the rectum, and 18 nonneoplastic rectoanal mucosa were randomly selected and immunostained for CK7 and CK20 with a standard avidin-biotin complex method. Immunoreactivity was recorded semiquantitatively. Cytoplasmic CK7 immunoreactivity was noted in 29 of 42 (69%) rectal glandular neoplasms (3 of 7 adenomas [43%] and 26 of 35 adenocarcinomas [74%]) and 9 of 18 (50%) nonneoplastic anorectal mucosal samples. In contrast, only 3 of the 11 (27%) colonic adenocarcinomas proximal to rectum were CK7 positive. Because of the relatively higher frequency of CK7 expression in rectal epithelial neoplasms, when CK7 is applied to distinguish primary colorectal versus metastatic origin, its reactivity should be interpreted with caution and should not be used as the sole evidence for excluding a rectal primary, particularly in tumors involving the rectal or pelvic region.

Topics: Adenocarcinoma; Antigens, Neoplasm; Colonic Neoplasms; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Metastasis; Rectal Neoplasms; Sensitivity and Specificity

A large percentage of cases of perianal Paget disease are associated with an internal cancer, most commonly rectal adenocarcinoma. Immunostains for cytokeratin 7, cytokeratin 20, and gross cystic disease fluid protein 15 are useful in identifying cases associated with rectal adenocarcinoma. The Paget cells and rectal adenocarcinoma cells of these lesions typically have a cytokeratin 7(+)/cytokeratin 20(+)/gross cystic disease fluid protein 15(-) immunophenotype. It is not known whether rectal adenocarcinoma unassociated with perianal Paget disease has the same cytokeratin profile as rectal adenocarcinoma associated with perianal Paget disease.. To evaluate the immunohistochemical cytokeratin 7 and 20 profile of resected rectal adenocarcinoma unassociated with perianal Paget disease as well as that of normal anal glands from hemorrhoidectomy specimens.. We performed immunohistochemistry for cytokeratins 7 and 20 on tissues from 30 cases of rectal adenocarcinoma unassociated with perianal Paget disease and 12 hemorrhoidectomy specimens from 12 cases with normal anal glands. We defined positive staining as any immunoreactivity within the neoplastic cells.. Twenty-six of 30 cases of rectal adenocarcinoma (87%) had a cytokeratin 7(-)/cytokeratin 20(+) immunophenotype, similar to the immunophenotype of cases of nonrectal large intestine adenocarcinoma. In 4 cases (13%), neoplastic cells coexpressed cytokeratins 7 and 20. Anal glands stained strongly for cytokeratin 7 but were negative for cytokeratin 20 in all cases, and the anal transitional zone mucosa had a similar immunophenotype.. Rectal adenocarcinoma unassociated with perianal Paget disease has a cytokeratin profile similar to that of nonrectal large intestine adenocarcinoma. These data suggest that rectal adenocarcinoma unassociated with perianal Paget disease has a different cytokeratin profile than rectal adenocarcinoma associated with perianal Paget disease.

Topics: Adenocarcinoma; Anal Canal; Colonic Neoplasms; Hemorrhoids; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Paget Disease, Extramammary; Rectal Neoplasms

Primary adenocarcinoma of the seminal vesicles is an extremely rare neoplasm. Because prompt diagnosis and treatment are associated with improved long-term survival, accurate recognition of this neoplasm is important, particularly when evaluating limited biopsy material. Immunohistochemistry can be used to rule out neoplasms that commonly invade the seminal vesicles, such as prostatic adenocarcinoma. Previous reports have shown that seminal vesicle adenocarcinoma (SVCA) is negative for prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PAP); however, little else is known of its immunophenotype. Consequently, we evaluated the utility of cancer antigen 125 (CA-125) and cytokeratin (CK) subsets 7 and 20 for distinguishing SVCA from other neoplasms that enter the differential diagnosis. Four cases of SVCA-three cases of bladder adenocarcinoma and a rare case of adenocarcinoma arising in a mullerian duct cyst-were immunostained for CA-125, CK7, and CK20. Three of four cases of SVCA were CA-125 positive and CK7 positive. All four cases were CK20 negative. All bladder adenocarcinomas and the mullerian duct cyst adenocarcinoma were CK7 positive and negative for CA-125 and CK20. In addition, CA-125 immunostaining was performed in neoplasms that commonly invade the seminal vesicles, including prostatic adenocarcinoma (n = 40), bladder transitional cell carcinoma (n = 32), and rectal adenocarcinoma (n = 10), and all were negative for this antigen. In conclusion, the present study has shown that the CK7-positive, CK20-negative, CA-125-positive, PSA/PAP-negative immunophenotype of papillary SVCA is unique and can be used in conjunction with histomorphology to distinguish it from other tumors that enter the differential diagnosis, including prostatic adenocarcinoma (CA-125 negative, PSA/PAP positive), bladder transitional cell carcinoma (CK20 positive, CA-125 negative), rectal adenocarcinoma (CA-125 negative, CK7 negative, CK20 positive), bladder adenocarcinoma (CA-125 negative), and adenocarcinoma arising in a mullerian duct cyst (CA-125 negative).

Topics: Adenocarcinoma; Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Transitional Cell; Cysts; Diagnosis, Differential; Genital Neoplasms, Male; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Mullerian Ducts; Prostatic Neoplasms; Rectal Neoplasms; Seminal Vesicles; Urinary Bladder Neoplasms

We report a case of intestinal hepatoid adenocarcinoma, confirmed by albumin m-RNA in situ hybridization, with subsequent metastatic spread to the liver in a male with a long-standing history of ulcerative colitis. This novel finding strongly suggests that ulcerative colitis can lead not only to conventional adenocarcinomas but also to hepatoid adenocarcinoma and highlights the mimicry of hepatocellular carcinoma by metastatic hepatoid adenocarcinoma liver nodules.

Topics: Adenocarcinoma; Adult; Albumins; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Colitis, Ulcerative; Colonic Polyps; Follow-Up Studies; Humans; In Situ Hybridization; Keratins; Liver Neoplasms; Lymphatic Metastasis; Male; Mucin-1; Rectal Neoplasms; RNA, Messenger

Primary adenocarcinoma of the urinary tract are uncommon. But secondary involvement of pyelocalyceal system by metastasis of colorectal origin is rare. We report a case of late rectal metastasis with renal pelvis growth presenting as a pyonephrosis. This study emphasizes the relevance of cytokeratin 7 and 20 immunostaining in such differential diagnosis.

Topics: Adenocarcinoma; Aged; Diagnosis, Differential; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Kidney Neoplasms; Male; Rectal Neoplasms

Lymph node metastasis is an important prognostic factor for rectal carcinoma, but only a few attempts at defining the relationship between lymph node micrometastases and prognosis have been made. The purpose of this study was to examine the correlation between the presence of micrometastases and prognosis in patients with rectal carcinoma. Six hundred forty-four lymph nodes were dissected from 42 patients with Dukes' B rectal carcinoma and stained immunohistochemically using a monoclonal antibody, CAM5.2, that binds cytokeratin. Clinicopathological factors, rate of recurrence, and prognosis were compared among patients with and without micrometastases. Micrometastases were detected in 19 lymph nodes (19 of 644 = 2.9%) from 9 patients (9 of 42 = 21.4%). The presence of micrometastases was not related to clinicopathological factors. There were significant differences in recurrence rates (5 of 9 versus 5 of 33, P = 0.02), relapse-free survival rates (P = 0.04), and 10-year survival rates (P = 0.03) between patients with and without micrometastases. Immunohistochemistry successfully identified micrometastatic foci in lymph nodes missed with conventional staining methods. The existence of micrometastases influenced the prognosis in patients with Dukes' B rectal carcinoma.

Topics: Antibodies, Monoclonal; Carcinoma; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Predictive Value of Tests; Prognosis; Rectal Neoplasms; Recurrence; Survival Rate

Patients with solitary rectal ulcer syndrome (SRUS) frequently present with a mass that can be misinterpreted as cancer. In contrast, the occurrence and characteristics of SRUS-like histopathology produced by underlying malignancy have not been reported in detail. We report seven patients whose rectal mass that was induced by infiltrating carcinoma showed only histopathologic changes of SRUS on initial mucosal biopsy specimens. Carcinoma was evident in subsequent specimens after one to five repeat biopsies with delay in diagnosis from 1 week to 18 months in six patients. In one patient, infiltrating carcinoma was suggested on the first biopsy specimen by immunohistochemistry for cytokeratin. Three of the patients had primary rectal adenocarcinoma, two had metastatic carcinoma from stomach or ovary, and two had direct invasion of anal squamous cell carcinoma or prostatic adenocarcinoma. We conclude that the histopathology of SRUS may occasionally represent a characteristic but nonspecific mucosal reactive change to a deeper seated malignancy. The terminology "solitary rectal ulcer syndrome/mucosal prolapse changes" with a cautionary note may be useful for reporting biopsy results to emphasize the possibility of underlying primary or metastatic malignancy in the differential diagnosis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Proctoscopy; Prostate-Specific Antigen; Rectal Diseases; Rectal Neoplasms; Rectal Prolapse; Retrospective Studies; Ulcer

Perianal Paget's disease is rare, and its relationship to an associated internal regional cancer has been ill defined. We analyzed the histologic and immunohistochemical features of perianal Paget's disease in 11 patients to determine the frequency and relationship of associated regional internal carcinoma and to gain insight into its histogenesis. Of five patients with documented rectal adenocarcinoma, it was discovered synchronously with the Paget's disease in four and, subsequently, in one. Paget's cells of signet ring type predominated in four cases. Intraepithelial glands with intraluminal dirty necrosis were present in four cases. The immunophenotype in four cases studied was cytokeratin (CK)7+/CK20+/gross cystic disease fluid protein- (GCDFP) in both the intraepithelial Paget's cells and the invasive rectal adenocarcinoma. Six patients did not have documented rectal carcinoma. The Paget's cells in four were CK7+/CK20-/GCDFP15+. Three of these had purely intraepithelial Paget's disease, and invasive or metastatic disease developed in none after wide local excision. Bilateral inguinal lymph node metastases developed in the fourth patient, and the patient died 8 months after diagnosis of Paget's disease. In two patients, the Paget's cells were CK7+/CK20+/GCDFP15-. Recurrent intraepithelial perianal Paget's disease developed in one patient at 7 months; the patient was alive without disease at 24 months, and the other patient had several intraepithelial recurrences of perianal Paget's disease, and, subsequently, a large perianal tumor of uncertain cell type developed at 108 months, which led to the patient's death. We conclude that there are two types of perianal Paget's disease. One type has endodermal differentiation with gastrointestinal-type glands containing intraluminal dirty necrosis, numerous signet ring cells, CK20 positivity, and GCDFP15 negativity. Such cases are especially likely to be associated with synchronous or metachronous rectal adenocarcinoma. The other type is a primary cutaneous intraepithelial neoplasm in which the Paget's cells display sweat gland differentiation, including GCDFP15 positivity; it generally lacks gastrointestinal-type glands, intraluminal dirty necrosis, and CK20 positivity. The CK7 is a sensitive, albeit nonspecific, marker for Paget's cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Rectal Neoplasms

The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer.. Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody.. Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases.. Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.

Topics: Adult; Aged; Aged, 80 and over; Colonic Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Rectal Neoplasms; Survival Analysis

Recent studies have shown that various tumor cells accumulate ubiquitin (Ub)-conjugated proteins, the profiles of which differ from those of normal cells. To identify the Ub-conjugated proteins accumulated specifically by human carcinoma cells, a two-dimensional immunoblot analysis of 31 surgically resected human primary colorectal carcinoma tissues was performed using an anti-Ub monoclonal antibody, KM691. Two distinct Mr 42,000 and 45,000 proteins in the Triton X-insoluble fractions of carcinoma tissues reacted with this antibody, whereas only one Mr 45,000 protein reacted in normal tissues. The Mr 42,000 Ub-conjugated proteins were specific to carcinoma tissues from 25 patients (80.6%). One of the purified Mr 42,000 proteins was digested with Achromobacter protease I. This protein was identified as a cytokeratin 8 (CK 8) fragment based on both molecular mass determination and molecular mass searching of Achromobacter protease I-digested fragments of proteins registered in a protein sequence data base. Two-dimensional immunoblot analysis with an anti-CK 8 antibody confirmed that all of the Mr 42,000 proteins were CK 8 degradation products. These results demonstrate that human colorectal carcinomas specifically accumulate Mr 42,000 Ub-conjugated CK 8 fragments. This accumulation was observed frequently not only in advanced (18/22, 81.8%), but also in early stage cases (7/9, 77.8%), suggesting that it occurs even in the early stages of colorectal carcinoma progression.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibody Specificity; Base Sequence; Colonic Neoplasms; Female; Humans; Immunoblotting; Keratins; Male; Middle Aged; Molecular Sequence Data; Molecular Weight; Neoplasm Proteins; Rectal Neoplasms; Sigmoid Neoplasms; Ubiquitins

Primary small cell undifferentiated carcinomas (SCUCs) are unusual tumors of the colon and rectum. Histologically, these lesions represent a spectrum of neuroendocrine differentiation, with oat cell carcinoma being the most primitive subtype and carcinoid tumors being the most differentiated. This observation is supported by immunohistochemical and ultrastructural findings. We report a case of SCUC of the rectum in a patient with ulcerative colitis. To date, there have been only two reported cases of primary SCUC associated with ulcerative colitis. Recent theories of tumorigenesis attribute most colorectal cancers to a single, pluripotential mucosal stem cell, regardless of the tumor's histologic type.

Topics: Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Colitis, Ulcerative; Fatal Outcome; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Keratins; Middle Aged; Neoplastic Stem Cells; Phosphopyruvate Hydratase; Rectal Neoplasms; Rectum; Synaptophysin; Tumor Suppressor Protein p53

Serum CYFRA21-1 levels were studied in 127 cases of colorectal cancer. The positive rates for serum CYFRA21-1 were 34.6% in primary colorectal cancer. There was a significant correlation between the positive rates of serum CYFRA21-1 and liver metastases, peritoneal dissemination, lymph node metastases, or clinical stage. The survival rate for patients in the CYFRA21-1 positive group was lower than those with CYFRA21-1 negative group. Among patients who underwent curative operation, patients is the CYFRA21-1 positive group gave a recurrence rate of 26.6%, against 9.4% in the CYFRA21-1 negative group. There was no correlation between serum CYFRA21-1 levels and serum CEA levels. These findings suggest that Serum CYFRA21-1 levels may be a useful indicator in estimating the prognosis for colorectal cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Colonic Neoplasms; Humans; Keratins; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Invasiveness; Prognosis; Rectal Neoplasms; Survival Rate

A rectal adenocarcinoma in a 22-year-old capped langur histologically resembling those in human cases is reported. An ill-defined diffuse tumor with fibrously firm rectal wall showed diffuse infiltrative growth of signet-ring cancer cells. Immunohistochemistry demonstrated positive staining for CEA, lysozyme, EMA, keratin and B72.3.

Topics: Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Signet Ring Cell; Cercopithecidae; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Microvilli; Mucin-1; Mucins; Muramidase; Neoplasm Proteins; Primate Diseases; Rectal Neoplasms

Immunocytochemistry was used in parallel with conventional cytology to detect circulating malignant epithelial cells in 42 patients undergoing resection for colorectal cancer. Preoperative peripheral and peroperative mesenteric venous blood samples were taken. Tumour cells were isolated on a density gradient and cytospins prepared. Slides were stained by conventional cytology (May-Grünwald-Giemsa) and by an indirect immunoperoxidase technique with the anticytokeratin antibody KG8.13. Using conventional cytology, definite morphological evidence of malignancy was observed in three patients and suspicious features in a further seven. Immunocytochemistry confirmed these findings in all three of the malignant but in only one of the suspicious cases. Counts of immunostained cytospins showed the concentration of tumour cells in blood samples from these four patients to be in the range 0-954 cells/ml. This study supports the use of immunological markers to detect and enumerate malignant cells. This method provides a powerful tool to investigate one aspect of the metastatic process.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Cell Count; Colonic Neoplasms; Female; Humans; Immunoenzyme Techniques; Intraoperative Period; Keratins; Male; Mesenteric Veins; Middle Aged; Neoplastic Cells, Circulating; Rectal Neoplasms

The distribution pattern of cytokeratin (CK) subtypes, an intermediate filament of cytoskeleton, was examined in adenomas and carcinomas of the colon and rectum. For the detection of the cytokeratin subtypes, monoclonal antibodies to the 54 Kd keratin polypeptide (CK No. 7 according to Moll's classification), 52.5 Kd (CK No. 8), 45 Kd (CK No. 18), and 40 Kd (CK No. 19) were used for immunohistochemical observation. Although No. 7 was positive in normal mucosa and adenoma with mild to moderate atypia, it could not be recognized in carcinoma. On the other hand the expression of No. 18 was confirmed in carcinoma, adenoma, and normal mucosa, and there were some differences in its distribution pattern in those with or without glandular formation and in areas showing infiltration of tumor cells. No. 18 expression was on the luminal side of normal colonic mucosa, adenoma, and well-differentiated adenocarcinoma; in the infiltrating area its reactivity was localized diffusely in the cytoplasm of tumor cells showing moderately or poorly differentiated adenocarcinoma cells. As to No. 8 and No. 19, they were recognized in normal mucosa, adenoma, and carcinoma. These results suggested the intimate relationship between expression of CK subtypes, cellular differentiation, and structural differentiation of colorectal carcinoma.

Topics: Adenocarcinoma; Adenoma; Colon; Colonic Neoplasms; Humans; Immunoenzyme Techniques; Intestinal Mucosa; Keratins; Rectal Neoplasms; Rectum

A patient with skin metastases several years after surgical treatment of carcinoma of the cervix and the rectum is presented. Comparative histology and immunohistochemical analysis with anti-cytokeratin antibodies implicated the carcinoma of the cervix as the source of the skin infiltrates. Based on this patient's case record, the use of anti-cytokeratin antibodies for identification and subtyping of epithelial or carcinoma cells is discussed with special reference to cytokeratin 7.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Combined Modality Therapy; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Staging; Neoplasms, Second Primary; Rectal Neoplasms; Skin; Skin Neoplasms; Uterine Cervical Neoplasms

The immunohistochemical expression of intermediate filaments was investigated in 56 carcinoid tumors from 50 cases including 31 rectal and 25 non-rectal sites. Cytokeratin was the most frequently expressed in 55 of the tumours. Only one tumour of the stomach was negative for cytokeratin. Neurofilament (68 kd and 160 kd) was positive in 25 (44.6%) tumours with no preferential pattern of expression in particular tumours. Vimentin was positive in 18 out of the 31 rectal carcinoids (58%), and 3 of the 25 non-rectal carcinoids (12%). There was a significant difference in vimentin immunoreactivity between rectal and non-rectal carcinoids. The coexpression of cytokeratin and neurofilament was 44.6% and that of cytokeratin and vimentin was 37.5%. The coexpression of all three types of intermediate filament was 35.5% in rectal carcinoids, but 8% in non-rectal carcinoids. The present study revealed coexpression of cytokeratin, neurofilament and vimentin in carcinoids and an especially high incidence of vimentin expression in those of rectal origin.

Topics: Carcinoid Tumor; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Neurofilament Proteins; Rectal 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

Flow cytometric DNA analysis using the anti-cytokeratin antibody was carried out in order to estimate more reliable measurement in single cell suspension obtained from solid tumors. It was difficult to detect a DNA aneuploidy with DI of 2.0 by one parameter analysis of DNA. Whereas it could be detected easily by using dual parameter analysis of cytokeratin and DNA. And also, the pattern of DNA multiploidy could be selected for cytokeratin positive cell population by gate analysis.

Topics: Antibodies; DNA, Neoplasm; Flow Cytometry; Humans; Keratins; Lung Neoplasms; Ploidies; Rectal Neoplasms; Tumor Cells, Cultured

The detection of early micrometastasis or disseminated single tumor cells poses a problem for conventional diagnosis procedures. Using a panel of monoclonal antibodies against cytokeratin and the 17-1A epithelial antigen we identified immunocytochemically tumor cells in bone marrow of patients with breast cancer (n = 155) and colorectal cancer (n = 57) at the time of surgery of the primary tumor. Monoclonal antibody CK2, recognizing the human cytokeratin component 18 in simple epithelia, appeared to be the most suitable reagent because of its negative reaction with bone marrow samples of the noncarcinoma patients (n = 75). Its specificity was further demonstrated in a double-marker staining procedure using an anti-leukocyte common antigen monoclonal antibody (T200) as counterstain. A comparative analysis showed that immunocytology was clearly superior to conventional cytology (n = 212) and histology (n = 39). In 9.5-20.5% of patients without distant metastasis, tumor cells could be detected in bone marrow. We found a significant correlation between tumor cells in bone marrow and conventional risk factors, such as distant metastasis or lymph node involvement. In a first approach toward immunotherapy we demonstrated in 3 patients that infused monoclonal antibody 17-1A can label single tumor cells in bone marrow in vivo. We then used this approach to follow up 7 patients undergoing 17-1A therapy in an adjuvant clinical trial.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Bone Marrow; Breast Neoplasms; Colonic Neoplasms; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Metastasis; Rectal Neoplasms

The search for tumour markers was intensified with the advent of monoclonal antibody technology. To date no tumour specific markers have been found. Despite this, monoclonal antibodies have helped to identify cells in terms of their origin and function and therefore added a different dimension to studies of both benign and malignant disease processes. Advances in molecular biology have made cooperation between scientists and clinicians in all branches of medicine essential in order to piece together a more complete picture of any disease. This article describes the production and characterisation of two epithelial specific monoclonal antibodies (CAM5.2 and CAM17.1) with potential clinical value by a surgeon temporarily transposed to a laboratory environment.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Colonic Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Lymphatic Metastasis; Rectal Neoplasms; Uterine Cervical Neoplasms

Five thousand seven hundred seventy-eight adenomas or adenomas containing carcinoma from 3215 patients were examined by routine histologic methods for the presence of epithelial metaplasias. Three forms of epithelial metaplasia were encountered: squamous cell metaplasia (0.44%), Paneth cell metaplasia (0.20%), and melanocytic metaplasia (0.017%). In several instances multiple forms of metaplasia were encountered in the same polyp. In those cases in which the paraffin blocks were available, a Grimelius stain was performed. Grimelius-positive cells were present in 63% of the adenomas containing a metaplastic cell type. All cases with Paneth cell differentiation were immunoreactive for lysozyme; all lesions containing areas of squamous differentiation were immunoreactive for keratin except 2. The histopathologic features of these cases are discussed, and it is concluded that rather than representing a true metaplastic process, Paneth cell, squamous cell, and melanocyte differentiation represent the full range of cellular differentiation that endodermally derived tissues can exhibit, particularly when they undergo neoplastic alterations.

Topics: Adenoma; Adult; Age Factors; Aged; Cell Differentiation; Colonic Neoplasms; Female; Histocytochemistry; Humans; Intestinal Polyps; Intestine, Large; Keratins; Male; Melanocytes; Metaplasia; Middle Aged; Muramidase; Rectal Neoplasms; Retrospective Studies; Sex Factors

Human epithelial cells contain, intermediate-sized filaments formed by polypeptides related to epidermal alpha-keratin ("cytokeratins") which are expressed in different combinations in different epithelia. Using cytoskeletal proteins from human biopsies and autopsies we have examined, by two-dimensional gel electrophoresis and immunoblotting experiments, the cytokeratin polypeptide patterns of diverse primary and metastatic carcinomas and have compared them with those of corresponding normal epithelial tissues and cultured cells. Five groups of carcinoma cytokeratin patterns can be discriminated. (1) Cytokeratins typical of simple epithelia (polypeptides Nos. 7, 8, 18, 19) are expressed, in various combinations, by many adenocarcinomas, for example those of gastrointestinal tract. (2) Cytokeratins typical of stratified epithelia (Nos. 1, 5, 6, 10, 11, 14-17) are found, in various combinations, in squamous cell carcinomas of skin and tongue. (3) Complex patterns showing polypeptides Nos. 7, 8, 18, 19, and one basic component (No. 5 or 6) are detected in certain carcinomas of the respiratory tract and the breast. (4) Complex patterns containing cytokeratins widespread in stratified epithelia (Nos. 4-6, 14-17) as well as components Nos. 8 and 19 occur in diverse squamous cell carcinomas derived from non-cornified stratified epithelia, with or without additional small amounts of cytokeratin No. 18. (5) Patterns of unusually high complexity can be found in some rare tumors as is shown for a cloacogenic carcinoma. No significant qualitative changes of expression of cytokeratins were found when primary tumors and metastases were compared. When compared with cytokeratin patterns of normal epithelia, carcinomas of the first type usually display a high degree of relatedness to the tissue of origin. Other carcinomas do not express some of the cytokeratins present in the tissue of their origin and, vice versa, certain components which are minor or apparently absent in normal tissue are major cytokeratins in the corresponding tumor. These differences may be explained by cell type selection during carcinogenesis, but changes of expression during tumor development cannot be categorically excluded. The possibility of cell type heterogeneity within a given tumor is also discussed. Similarly complex patterns of cytokeratin polypeptides have been noted in certain cultured human carcinoma cell lines (e.g., A-431, RPMI 2650, Detroit 562, A-549) and can also be observed in cel

Topics: Breast Neoplasms; Carcinoma, Squamous Cell; Cell Line; Cytoskeleton; Digestive System Neoplasms; Electrophoresis, Polyacrylamide Gel; Epithelium; Humans; Keratins; Liver Neoplasms; Lymphatic Metastasis; Neoplasms; Peptides; Rectal Neoplasms; Respiratory Tract Neoplasms; Urinary Bladder Neoplasms

Epithelia-derived tumors (carcinomas) can be distinguished from mesenchymally derived tumors by the presence of intermediate-sized filaments of the cytokeratin type, which usually coincides with the absence of other types of intermediate-sized filaments such as vimentin filaments. In the course of diagnostic examinations of human tumors, using immunofluorescence microscopy, we have come across a case of an unusual carcinoma (Primary tumor and lymph node metastasis) positively stained not only with cytokeratin antibodies but also with immunoglobulins present in vimentin antisera. Therefore, this tumor, a cloacogenic carcinoma apparently derived from the rectal-anal transitional region, has been examined in greater detail using both immunofluorescence microscopy and immuno-electron microscopy as well as gel electrophoretic analysis of cytoskeletal polypeptides from total tumor tissue and from microdissected nodules enriched in carcinoma cells. The unusual reaction of the carcinoma cells with immunoglobulins present in seven different (rabbit or guinea pig) antisera raised against vimentin, has been found to be diminished after absorption on purified cytokeratin or total epidermal cytoskeletal material, but not after absorption on purified vimentin. Gel electrophoretic analysis of tumor cytoskeletons showed an unusual complex pattern of cytokeratin polypeptides containing relatively large (Mr 68,000 and Mr 58,000) neutral-to-slightly basic cytokeratins, as are typically found in epidermis and other stratified squamous epithelia, as well as several smaller acidic cytokeratins, including a Mr 40,000 polypeptide found in certain nonstratified epithelial such as colon and small intestine. Total tumor also showed the inclusion of some vimentin which, however, was significantly decreased in analysis of excised carcinoma nodules. Examining antibody binding to polypeptides separated by gel electrophoresis and blotted on nitrocellulose paper, we have found that antisera raised against vimentin contained not only vimentin antibodies but also immunoglobulins which specifically bound to the largest cytokeratin component. We conclude that the unusual reaction of immunoglobulins present in vimentin antisera with cytokeratin filament bundles does not represent specific binding to vimentin in these carcinoma cells, but is due to a component obviously widespread in vimentin antisera which binds specifically to a cytokeratin present in this type of tumor but not in most othe

Topics: Aged; Anus Neoplasms; Carcinoma, Transitional Cell; Cytoskeleton; Female; Humans; Isoelectric Point; Keratins; Molecular Weight; Muscle Proteins; Rectal Neoplasms; Vimentin