Cytokeratins 20 and 7 in the differential diagnosis of metastatic carcinoma in cytologic specimens

A series of 33 tumor cases (13 fine-needle aspirates and 20 effusion specimens) were evaluated for the expression of two cytokeratin (CK) subtypes; CK 20, expressed primarily in tumors of the GI tract, mucinous ovarian tumors and transitional cell carcinomas, and CK 7, found chiefly in non-GI tract adenocarcinomas, including breast and lung. CK 20 expression was demonstrated immunocytochemically in seven of seven metastatic colon and two of three metastatic transitional cell carcinomas tested. CK 20 was absent in all metastatic carcinomas of breast, ovary, lung, and uterus examined (23 cases). Anti-CK 7 stains were negative in four of six metastatic colonic carcinomas, with equivocal results in the remaining two cases. Metastatic lung, breast, and ovarian carcinomas were strongly positive for CK 7. This study demonstrates that the combined use of anti-CK 20 and anti-CK 7 antibodies is highly sensitive and specific for metastatic colonic adenocarcinoma in cytologic material and thus could play an important role in distinguishing this entity from other common primary carcinomas. Diagn. Cytopathol. 16:132–136, 1997. © 1997 Wiley-Liss, Inc.     

The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract

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.     

The clinical relevance of cytokeratin phenotyping in needle biopsy of liver metastasis

Although cytokeratin (CK) phenotyping of metastatic tumors is now routine in many laboratories, the clinical relevance of the procedure has seldom been addressed. We carried out a prospective clinical study of 134 consecutive cases of metastatic adenocarcinoma of the liver diagnosed by needle biopsies stained routinely for CK20 and CK7. The most probable localization of the primary tumor, deduced from this staining pattern, was stated in the original pathology report. The present study compared this assignment with the information available at the time of interpretation of the liver biopsy, to the results of the subsequent clinical investigation, and to the officially reported cause of death as outcome. As expected, the primary tumors were localized in the colon or in the rectum in 85% (34/40) of the CK20+/CK7- metastases. The definite diagnosis remained metastatic colorectal carcinoma in 83% (15/18) of the cases with diagnosed colorectal cancer before the liver biopsy. In the cases without a known primary tumor when the liver biopsy was interpreted, primary colorectal localization was accurately predicted in 86% (19/22) of the patients. Compared to the outcome, 77% (36/47) of the CK20+/CK7+ metastases had the expected pancreaticobiliary primary localization in 83% (30/36) without any primary tumor being known at the time of interpretation of the liver biopsy. In contrast, the majority of CK20- metastatic carcinomas had an unexpected primary localization, 50% (16/32) in the CK20-/CK7+ and 60% (9/15) in the CK20-/CK7- subgroup. In addition, the origin of the liver metastasis remained unknown in 37% (12/32) of CK20-/CK7+ cases. Thus, the CK20+/CK7- phenotype indicates a colorectal origin of the liver metastasis with considerable accuracy and independently of the available clinical information. The same is true for CK20+/CK7+ metastases, which indicate primary tumor localization in the pancreas or in the biliary tree. The results in the CK20- subgroups of the liver metastases are disappointing and cannot substantially help the clinical investigation.     

Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract

AIMS: The differential expression of cytokeratin (CK) 7 and 20 by carcinomas may help in determining the primary site of a metastatic tumour. The aim of this study was to extend the published data on CK7 and CK20 expression in epithelial neoplasms of the gastrointestinal tract by considering the degree of differentiation and including some unusual neoplasms. METHODS AND RESULTS: Cases referred to the Armed Forces Institute of Pathology were studied prospectively for immunohistochemical expression of CK7 and CK20. Lesions from 105 patients were analysed. Adenocarcinomas of the upper gastrointestinal tract were positive for both CK7 and CK20 in 78% of cases; only poorly differentiated lesions were CK7-. Well-differentiated and moderately differentiated adenocarcinomas of the large intestine, including appendix, were CK7-/CK20+ in the great majority of cases, as were goblet cell carcinoids, but half of the poorly differentiated adenocarcinomas exhibited aberrant expression, as did most of the mixed goblet cell carcinoid/adenocarcinomas. All five high-grade neuroendocrine carcinomas were negative for both CK7 and CK20. CONCLUSIONS: Not only the site but also the grade and histological type of a gastrointestinal carcinoma should be considered when assessing cytokeratin phenotype.     

Patterns of distribution of cytokeratins 20 and 7 in special types of invasive breast carcinoma: a study of 123 cases

Metastatic adenocarcinomas of unknown primary site are a common clinical problem. Invasive ductal carcinomas of the breast and some special types of invasive breast carcinoma are common sources of metastases. Immunohistochemical algorithms, such as a combination of cytokeratins 20 and 7, can be helpful in this situation. Detailed phenotyping of the different types and subtypes of primary invasive carcinomas and their metastases is an essential prerequisite for a successful search for an unknown primary tumor. A series of 123 primary invasive breast adenocarcinomas of special type and of 27 lymph node metastases was analyzed. Sections of selected blocks were stained with two monoclonal cytokeratin antibodies (CK20 and CK7) and evaluated as negative (no staining), focally positive or diffusely positive. Of the 123 carcinomas, 113 (92%) proved to be CK20 negative. Three of 82 (4%) invasive lobular carcinomas, three of 11 (27%) mucinous carcinomas, one of 10 (10%) tubular carcinomas, and one invasive papillary carcinoma stained diffusely with CK20. Additionally, a tubulolobular carcinoma and a medullary carcinoma showed focal CK20 positivity. One hundred twenty (98%) of the 123 tumors were CK7 positive, five of them only focally. One of the four solid invasive lobular carcinomas, one medually carcinoma, and one invasive papillary carcinoma were completely negative for CK7. Only two cases, one mucinous and one invasive papillary carcinoma, exhibited the CK20(+)/CK7(-) ("colorectal") pattern. One of the lymph node metastases was CK20(+); another was CK7(-). Like their ductal counterparts, invasive breast carcinomas of special type are usually CK20(-)/CK7(+); they generally retain this phenotype in their metastases. However, there are CK20-positive special-type breast carcinomas that can be confused with gastrointestinal or pancreaticobiliary carcinoma in metastases, especially if they are mucinous or invasive lobular.     

一组细胞角蛋白抗体在胸腹腔积液中的表达及其鉴别诊断价值

目的:探讨一组细胞角蛋白抗体在胸腹腔积液中的表达情况及其临床应用价值。方法:选取72例胸腹腔积液标本,其中腺癌30例,鳞癌22例,反应增生性间皮细胞22例,应用细胞免疫化学SP法检测细胞角蛋白CK(AE1/AE3)、细胞角蛋白5/6(CK5/6)、细胞角蛋白18(CK18)的表达。结果:三种抗体在反应增生性间皮细胞、腺癌细胞、鳞癌细胞中阳性率分别是CK(AE1/AK3):10.0%,73.3%,68.2%;CK5/6:60.0%,6.7%,77.3%;CK18:0,80.0%,4.5%。组合CK(AE1/AE3)(-)、CK5/6(+)、CK18(-)检测间皮细胞的敏感性为93.3%,特异性为80.2%;CK5/6(-)、CK18(+)检测腺癌细胞的敏感性为84.7%,特异性为93.6%;CK(AE1/AE3)(+)、CK5/6(+)、CK18(一)检测鳞癌细胞的敏感性为86.4%,特异性为92.8%。结论:多项细胞角蛋白联检提高了诊断反应增生性间皮细胞、腺癌细胞、鳞癌细胞的敏感性和特异性,可辅助细胞形态学对于良恶性胸腹腔积液的鉴别诊断。     

Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas

Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are low molecular weight cytokeratins. The expressions of CK7 and CK20 have been studied in various primary and metastatic carcinomas. Their expression patterns may help to distinguish the site of origin of metastatic carcinomas. We investigated the expressions of CK7 and CK20 in 196 cases of colorectal carcinoma. Paraffin sections of 196 colonic adenocarcinomas were randomly selected, retrieved, and immunostained for CK7 and CK20 with a standard avidin-biotin complex method. CK7 was expressed in 34/196 (17.3%) and CK20 in 159/196 (81.1) cases of colorectal adenocarcinoma. CK7−/CK20+ had the greatest proportion (65.8%) in colorectal carcinomas. The CK7+/CK20+ immunophenotype was identified in 30/196 (15.3%), CK7−/CK20− in 33/196 (16.9%), and CK7+/CK20− in 4/196 (2%) colon adenocarcinomas. The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histological grade, location of the tumor, and lymph node metastasis. CK20 positivity was more common in low grade carcinomas than in high grade carcinomas (85.1% versus 47.6%) and in rectal and sigmoid carcinomas than in proximal colon carcinomas (88.2% versus 63.2% and 88.9% versus 63.2%, respectively). Furthermore, CK7 expression was more common in tumors with lymph node metastasis than in non-metastatic tumors (25.3% versus 11%). In conclusion, a considerable number of colorectal carcinomas showed reactivity to CK7 (17.3%) or no reactivity to CK20 (18.9%). Therefore, CK7 positivity or CK20 negativity does not rule out a colorectal origin of metastatic carcinoma.     

Cytokeratin 20-positive large cell neuroendocrine carcinoma of the colon

Herein is presented a case of cytokeratin (CK) 20-positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron-dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors' knowledge, the present case is the first CK 20-positive, CK 7-negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma.     

Cytology of metastatic cervical squamous cell carcinoma in pleural fluid: Report of a case confirmed by human papillomavirus typing

Cervical squamous cell carcinomas are rarely the cause of malignant effusions. Their identification can be relatively easy when keratinizing atypical squamous cells are present, but may be very difficult when only nonkeratinizing malignant cells are present. We present the case of a 47‐year‐old woman who presented with a large left pleural effusion after having recently completed chemoradiation therapy for stage IIB cervical squamous cell carcinoma. Cytologic examination of the fluid showed a uniform population of single atypical cells with finely vacuolated cytoplasm, ectoendoplasmic demarcation, cell‐in‐cell arrangements, and short rows of cells with intervening “windows,” all features reminiscent of mesothelial cells. No keratinization or three‐dimensional cell clusters were identified. A panel of immunohistochemical stains was performed on the cell block material, and the atypical cells were positive for cytokeratin 5/6, p63, and p16 but not for cytokeratin 7, calretinin, WT1, or Ber‐EP4 or TTF1. These findings were consistent with metastatic squamous cell carcinoma. HPV DNA determination and typing by PCR confirmed the presence of HPV16 in an aliquot of pleural fluid. This is to our knowledge the first reported case of pleural fluid involved by metastatic squamous cell carcinoma where HPV DNA testing was used to confirm the origin of the metastasis. Despite its rarity, metastatic nonkeratinizing squamous cell carcinoma should be considered when a single cell population of large atypical cells is found in effusions. Immunoperoxidase stains and HPV testing can be performed to establish the diagnosis and confirm the origin from a cervical primary. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Cytokeratin CK 7 and CK 20 expression in pituitary adenomas

The pattern of immunohistochemical expression of cytokeratins 7 (CK 7) and 20 (CK 20) is commonly used to assess possible primary sites of metastatic carcinomas. Because pituitary tumors are almost always benign, there has been little interest in their cytokeratin profile. However, we recently reported the use of CK 7/20 expression to document malignant progression and metastasis of a pituitary tumor, indicating the potential diagnostic usefulness of the CK 7/20 profile of pituitary adenomas. We analyzed CK 7/20 expression in 97 pituitary adenomas subclassified by immunohistochemical hormone expression. In about 90% of all subtypes, CK 7 was either negative or reactive in only a few scattered cells. Corticotrophs and sparsely granulated growth hormone-positive adenomas were consistently CK 20 positive (and CK 7 negative) whereas all other subtypes were almost always CK 20 negative. This CK 20-positive, CK 7-negative profile is previously described consistently only in colonic adenocarcinomas. This study documents that subtypes of pituitary adenomas have different CK 7/20 profiles. Whereas this pattern is likely to have diagnostic usefulness in only rare adenomas, the presence of a unique CK signature in corticotrophs and sparsely granulated growth hormone-positive adenomas, subtypes particularly noted for invasive and aggressive behavior, merits further investigation.     

An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: I. cytokeratin profile in 42 cases

Expression of cytokeratin (CK) profiles in primary signet-ring cell carcinoma (SRCC) of the stomach and colorectum have rarely reported; only two such studies are present in the world literature. Herein, an immunohistochemical study on cytokeratin (CK) expression was performed in 42 cases of primary SRCC of the stomach (30 cases) and colorectum (12 cases). SRCC was defined as an adenocarcinoma in which more than 50% adenocarcinoma cells showed SRCC phenotype with prominent intracytoplasmic mucins. In the gastric SRCC, the expression of CK was as follows; CK AE1/3 (30/30, 100%) CK CAM5.2 (30/30, 100%), CK 34BE12 (0/30, 0%), CK5/6 (2/30, 7%), CK7 (26/30, 89%), CK8 (12/30, 40%), CK14 (0/30, 0%), CK18 (30/30, 100%), CK19 (2/30, 7%), and CK20 (3/30, 10%). In the colorectal SRCC, the expression of CK was as follows; CK AE1/3 (12/12, 100%) CK CAM5.2 (12/12, 100%), CK 34BE12 (0/12, 0%), CK5/6 (0/12, 10%), CK7 (2/12, 17%), CK8 (3/12, 25%), CK14 (0/12, 0%), CK18 (12/12, 100%), CK19 (7/12, 58%), and CK20 (8/12, 67%). A statistical analysis showed that significant differences of CK expression between the gastric SRCC and colorectal SRCC were observed in CK7 (stomach 67% vs. colorectum 17%), CK19 (7% vs. 42%) and CK20 (13% vs. 67%); gastric SRCC tended to express CK7, but not CK19 and CK20, while colorectal SRCC tended to express CK19 and CK20, but not CK7. In gastric SRCC, CK7+/CK20- pattern was as follows: CK7+/CK20- (24/30, 81%), CK7+/CK20+ (2/30, 6%), CK7-/CK20+ (1/30, 3%), and CK7-/CK20- (3/30, 10%). CK7/CK19 patterns in gastric SRCC were as follows; CK7+/CK19- (25/30, 83%) CK7+/CK19+ (1/30, 3%), CK7-/CK19+ (1/30, 3%), CK7-/CK19- (3/30, 10%). In colorectal SRCC, the CK7/CK20 patterns were as follows: CK7+/CK20- (2/12, 17%), CK7+/CK20+ (0/12, 0%), CK7-/CK20+ (8/12, 66%), and CK7-/CK20- (2/12, 17%). The CK7/CK19 pattern in colorectal SRCC was as follows; CK7+/CK19- (1/12, 8%), CK7+/CK19+ (1/12, 8%), CK7-/CK19+ (6/12, 50%), and CK7-/CK19- (4/12, 34%). Statistical data indicated that CK7+/CK20- and CK7+/CK19- patterns were significantly prevalent in gastric SRCC, and CK7-/CK20+, CK7-/CK19+ and CK7-/CK20- patterns dominated significantly in colorectal SRCC. CK expression has been studied largely in terms of CD7/CK20 expression pattern in various carcinomas. The present study provided possible usefulness of CK7/19 expression status in various carcinomas including SRCC.     

CK7+/CK20- immunoexpression profile is typical of salivary gland neoplasia

AIMS: To evaluate cytokeratin (CK) 7/20 expression patterns in salivary gland neoplasia. METHODS AND RESULTS: Formalin-fixed paraffin embedded tissue from 153 salivary gland tumours were evaluated for CK7/20 immunoreactivity. The tumours included pleomorphic adenoma (n = 24), myoepithelioma (n = 9), papillary cystadenoma (n = 3), oncocytoma (n = 2), adenoid cystic carcinoma (n = 22), mucoepidermoid carcinoma (n = 21), polymorphous low-grade adenocarcinoma (n = 21), carcinoma ex-pleomorphic adenoma (n = 11), acinic cell carcinoma (n = 17), epimyoepithelial carcinoma (n = 7), oncocytic carcinoma (n = 3), hyalinizing clear cell carcinoma (n = 1), papillary cystadenocarcinoma (n = 1), salivary duct carcinoma (n = 3), adenocarcinoma (not otherwise specified) (n = 4) and squamous carcinoma (n = 4). Immunohistochemical procedures were performed using monoclonal antibodies CK7 (OV-TL 12/30), CK20 (Ks 20.8) and M3515 cytokeratin (AE1/AE3) in the presence of appropriate controls. The results were expressed semiquantitatively, according to the estimated percentage of positive tumour cells: 1+, 5-25%; 2+, 26-75%; and 3+, 76-100%. All salivary gland neoplasms showed a CK7+/CK20- immunoprofile ranging from 5 to 100%. Squamous carcinoma showed negative CK7/20 immunoexpression. CONCLUSIONS: Although the CK7/20 immunoprofile is not useful in distinguishing the various types of salivary gland neoplasms or between benign and malignant salivary gland tumours, it may facilitate differentiation of primary salivary gland neoplasia from metastatic tumours and squamous carcinoma, and the diagnosis of metastatic salivary gland tumours.     

The cytokeratin profile of medullary carcinoma of the breast

AIMS: The cytokeratin (CK) phenotype and vimentin expression of 31 medullary carcinomas was studied using commercially available antibodies on archived material. Comparing the phenotype of typical and atypical tumours and the phenotype of metastases, the biological significance of cytokeratin and vimentin expression in medullary carcinomas of the breast was determined. METHODS AND RESULTS: Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to vimentin were used. All the typical and atypical medullary carcinomas and the metastases (10 cases) stained negatively for CK4 and positively for CK8-18 (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative. Twelve per cent of the tumours contained CK14. Twenty-five per cent of the typical, 43% of the atypical and 20% of the metastatic medullary carcinomas showed CK5-6 positivity. No association between the cytokeratin-vimentin profile of the tumours and axillary node metastases, tumour size or oestrogen receptor status was found but instability of CK expression was demonstrated by comparing the primary tumours with their metastases. CONCLUSIONS: : Medullary carcinomas of the breast express all the glandular type CKs including CK19 and additionally a proportion of the tumours expresses some of the CKs typical for myoepithelial cells. There was no correlation with prognostic factors.     

Colonic adenocarcinoma metastatic to the thyroid gland: a case report with immunohistochemical investigation.

Clinically evident metastases of carcinomas to the thyroid gland are rare, particularly from a colorectal primary tumor. We present a case of colonic adenocarcinoma metastatic to the thyroid gland with histopathologic and immunohistochemical findings. A 68-year-old woman with a history of Dukes' stage B colon carcinoma presented a mass in the thyroid gland. The tumor was confirmed to be metastatic adenocarcinoma from the colon. The immunohistochemical findings demonstrated positive staining for cytokeratin 20, low-molecular-weight cytokeratin, villin and carcinoembryonic antigen, but stains were negative for cytokeratin 7 and thyroglobulin.     

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary

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.     

CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray

The ability to use archival tissue to test externally valid hypotheses of carcinogenesis is dependent on the availability of population-based samples of cancer tissue. Tissue microarrays (TMAs) provide an efficient format for developing population-based samples of tissue. A TMA was constructed consisting of archival tissue from patients diagnosed with invasive colorectal cancer in the state of Hawaii in 1995. The population representativeness of the TMA was evaluated by comparing patient and clinical characteristics of TMA cases to that of all cases of colorectal carcinoma diagnosed statewide in 1995. Cytokeratin 20 (CK20) and cytokeratin 7 (CK7) immunohistochemistry was used to validate the utility of the TMA, and the expression of these proteins was correlated with patient and tumor characteristics. The TMA comprised tissue specimens from 286 patients representing 47% of all invasive cases diagnosed statewide in 1995. TMA cases were comparable to all invasive colorectal cases statewide with respect to age, sex, race/ethnicity, anatomic site, and survival. There were some differences between TMA cases and all cases with respect to tumor stage, histological classification, and treatment. There were significant differences in the relative expression of CK20 and CK7 proteins between malignant and normal tissues and by tumor stage. Advanced cancers were more likely to have CK20+/cytokeratin 7+ (CK7+) profiles than early-stage cancers, which were predominantly CK20+/cytokeratin 7- (CK7-). CK7+ expression was not correlated with anatomic location of carcinomas. This well-characterized TMA offers a powerful tool for testing hypotheses regarding colorectal carcinogenesis, including the identification of potential markers of neoplastic development and progression.     

Differentiation of ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma by immunostaining with beta-catenin

AIMS: To investigate whether localization of beta-catenin is helpful in differentiating primary ovarian mucinous carcinoma and colorectal adenocarcinoma metastatic to the ovary. Extra-ovarian cancers which metastasize to the ovaries, especially from colorectal adenocarcinoma, frequently mimic primary ovarian carcinomas, particularly endometrioid and mucinous types. Distinguishing primary ovarian carcinoma from metastatic colorectal carcinoma is important for both therapeutic and prognostic reasons. Even after thorough histological examination, metastatic colorectal adenocarcinomas are still often mistaken for primary ovarian adenocarcinomas. Although some tumour makers have been advocated and are helpful in most cases, sometimes the distinction between primary mucinous carcinoma and metastatic colorectal carcinoma remains a problem. Activation of Wnt signalling through mutations of APC or beta-catenin is a key event in the development of colorectal cancer. These mutations lead to nuclear localization of beta-catenin, which can be demonstrated immunohistochemically. METHODS AND RESULTS: Formalin-fixed paraffin-embedded specimens from 43 primary ovarian mucinous carcinomas and 23 metastatic colorectal adenocarcinomas were included in this study. Sections were immunostained with antibodies to beta-catenin, cytokeratin (CK)7, CK20 and carcinoembryonic antigen (CEA). Nuclear localization of beta-catenin was found in 83% (19/23) of metastatic colorectal cancers and 9% (4/43) of ovarian mucinous carcinomas. Ovarian mucinous carcinomas were usually positive for CK7 (34/43, 79%). For comparison, 40 non-mucinous carcinomas of the ovary and 42 metastatic adenocarcinomas from other organs were also immunostained with antibodies against beta-catenin. Although nuclear localization of beta-catenin was occasionally seen in non-mucinous carcinoma of the ovary and metastatic adenocarcinoma from other organs, such tumours were usually distinguishable by their clinicopathological picture and rarely raised diagnostic problems. CONCLUSIONS: Immunostaining of beta-catenin is a useful marker for differentiating between ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma.     

恶性上皮性肿瘤中CK20的表达及其临床意义

目的　研究单克隆抗体CK2 0在恶性上皮性肿瘤和卵巢转移性腺癌组织中的表达及其意义。方法　应用S P法对鼻咽非角化性癌、乳腺浸润性导管癌、肺的鳞癌和腺癌、卵巢黏液性囊腺癌、胃腺癌和结肠直肠腺癌各组总计 6 7例和 4 1例分别进行了CK2 0和CK19检测。结果　CK2 0阳性率 :肺腺癌 1/ 7(14 3% ) ,卵巢浆液性和黏液性腺癌 3/ 12 (33 3% ) ,胃腺癌 3/ 9(33 3% ) ,结肠直肠腺癌组 2 1/ 2 2 (95 5 % ) ,其他癌组织均呈阴性。结肠直肠腺癌组组与其他各组间比较差异有显著性 (P <0 0 1)。CK19在上述 4 1例癌组织中均呈强阳性表达。结论　CK2 0表达对鉴别结肠腺癌和直肠腺癌与肺腺癌和乳腺浸润性导管癌具有高度特异性和较高的敏感性 ;CK2 0高表达对鉴别卵巢原发性腺癌与卵巢的结肠腺癌或直肠腺癌转移具有一定的意义