Cytokeratin 7 and Cytokeratin 20 Expression in Epithelial Neoplasms

Cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) are low molecular weight cytokeratins. Their anatomic distribution is generally restricted to epithelia and their neoplasms. We surveyed 435 epithelial neoplasms from various organ systems by immunohistochemistry using CK 7 and CK 20 monoclonal antibodies. Expression of CK 7 was seen in the majority of cases of carcinoma, with the exception of those carcinomas arising from the colon, prostate, kidney, and thymus; carcinoid tumors of the lung and gastrointestinal tract origin; and Merkel cell tumor of the skin. The majority of cases of squamous cell carcinoma of various origins were negative for CK 7, except cervical squamous cell carcinoma, in which 87% of cases were positive. Approximately two thirds of cases of malignant mesothelioma were CK 7-positive. CK 20 positivity was seen in virtually all cases of colorectal carcinomas and Merkel cell tumors. CK 20-positive staining was also observed in cases of pancreatic carcinomas (62%), gastric carcinoma (50%), cholangiocarcinomas (43%), and transitional cell carcinomas (29%). The expression of CK 20 was virtually absent in carcinomas from other organ systems and in malignant mesothelioma. CK 7- and CK 20-negative epithelial neoplasms included adrenal cortical carcinoma, germ cell tumor, prostate carcinoma, renal cell carcinoma, and hepatocellular carcinoma.

INTRODUCTION

The most common malignancies are derived from simple epithelia of the breast, lung, colon, prostate, ovaries, and endometrium. Carcinomas from these sites usually metastasize to regional lymph nodes and other organs, such as lung, brain, liver, and bone. The diagnosis of the metastatic carcinoma of unknown origin can be very difficult. The determination of the primary site of the metastasis is a challenge to both oncologists and pathologists, having potentially important clinical and therapeutic consequences.

Many tumor markers have been developed in the past two decades as immunohistochemical aids to the diagnosis of carcinoma. Some of these tumor markers, such as prostate specific antigen (PSA), are very organ specific. Others, such as carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA), although widely used, lack organ specificity. Although the expression of cytokeratins (CKs) is generally confined to epithelia and their neoplasms, they are not specific tumor markers. However, the highly diverse expression patterns of CKs have been correlated with different pathways of epithelial differentiation, and thereby allow the accurate and sophisticated classification of epithelial cells into different subtypes. During cell transformation and tumor development, this cell type specificity of cytokeratins is largely conserved.

The diverse and unique expression of CK 7 and CK 20 in carcinomas has been found to be useful in the differential diagnosis of some carcinomas of epithelial origin. Studies have shown that the different expression patterns of CK 7 and CK 20 are among the most discriminant markers in: (1) the differential diagnosis between metastatic colon and ovarian adenocarcinomas ; (2) the differential diagnosis between Merkel cell tumor of skin and small cell carcinomas of other origins; and (3) the differential diagnosis between lung, endometrial, and breast adenocarcinomas and colon adenocarcinoma. Studies of CK 7 and CK 20 expression in other epithelial carcinomas have also been explored in the past ten years. However, most of these studies have either involved few cases or studied limited organ systems. One relatively comprehensive study has been reported, but the reproductivity of these findings has not been confirmed in other laboratories, and even a previous large study only studied a limited number of organ systems.

Source :

Peiguo Chu M.D., Ph.D, Emerald Wu B.S. and Lawrence M Weiss M.D. Division of Pathology, City of Hope National Medical Center, Duarte, California

Correspondence: Lawrence M. Weiss, M.D., Division of Pathology, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010. fax: 818-301-8145