COORDINATE EXPRESSION OF CYTOKERATIN-7 AND CYTOKERATIN-20 DEFINES UNIQUE SUBSETS OF CARCINOMAS

We tested the hypothesis that the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) could distinguish among carcinoma s arising from different primary sites. A total of 384 cases of carcin omas primary to various organs, as well as 16 cases of malignant mesot helioma, were evaluated using commercially available monoclonal antibo dies and an avidin-biotin immunoperoxidase technique. The subset of tu mors strongly expressing both CK 7 and CK 20 included virtually all bl adder transitional cell carcinomas and the majority of pancreatic aden ocarcinomas; the tumors negative for both CK 7 and CK 20 were largely restricted to hepatocellular, prostate, and renal cell carcinomas in a ddition to squamous cell and neuroendocrine carcinomas of lung. The CK 7-/CK 20+ immunophenotype, however, was highly characteristic of aden ocarcinomas of colorectal origin, whereas CK 7+/CK 20- immunophenotype was typically seen in the vast majority of carcinomas arising from ot her sites, including ovary, endometrium, breast, and lung, as well as malignant mesothelioma. Gastric carcinomas were the most heterogeneous subgroup with respect to CK 7/CK 20 immunophenotype. In the subset of mucinous tumors, striking immunophenotypic differences were noted amo ng those primary to the breast (CK 7+/CK 20-), gastrointestinal tract (CK 7-/CK 20+), and ovary (CK 7+/CK 20+). In all cases investigated, t his CK immunophenotype was invariant in metastatic vs. primary tumors. It is concluded that, in the appropriate clinical setting, the CK 7/C K 20 immunophenotype of carcinomas is a valuable diagnostic marker in the determination of primary site of origin.