TRACING THE ORIGIN OF ADENOCARCINOMAS WITH UNKNOWN PRIMARY USING IMMUNOHISTOCHEMISTRY - DIFFERENTIAL-DIAGNOSIS BETWEEN COLONIC AND OVARIAN CARCINOMAS AS PRIMARY SITES

To discriminate adenocarcinoma metastases originating from either colo n or ovary, a panel of immunohistochemical markers was evaluated. For this purpose, paraffin sections from 157 primary and metastatic coloni c and ovarian carcinomas were immunostained. These cases were divided into a learning group of 46 colonic and 54 ovarian carcinomas and a te st group of 29 colonic and 28 ovarian carcinomas, including all metast atic tumors, among which were five with unknown primary site at the ti me of testing. The sections were immunostained with antibodies against carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), cytokeratin 20 ( CK20), CA 125, vimentin, and CA 19.9. Staining results were expressed as the product of staining intensity and percentage of positive tumor tells. Stepwise discriminant analysis was applied on the learning set to obtain a classification function for both tumors. The validity of t he classification function was evaluated using the test set. There was considerable overlap in immunostaining for both tumor types, but colo nic carcinomas were typically positive for CEA and CK20 and negative f or CK7 and CA125. Ovarian carcinomas were typically positive for CK7 a nd CA125 and negative for CEA and CK20. Tn discriminant analysis, the best combination of markers appeared to be CK7 and CEA. Only one sampl e of the test group (2%) was misclassified. Taking learning and test g roups together, 136 of the 157 samples (87%) were correctly classified with high posterior probability (PP > .8). However, from the 28 mucin ous ovarian carcinomas, only 19 (68%) could correctly be classified wi th high PP. When excluding the nonmucinous ovarian carcinomas from the analysis, overall 87 of 103 (84.5%) of the samples were correctly cla ssified (PP > .8) with a combination of CEA, CK7, and also vimentin. F rom the 28 mucinous ovarian carcinomas, only two (7%) were misclassifi ed, and four could not be classified with sufficient certainty. In nei ther analysis did CK20, CA125, or CA19.9 emerge as discriminatory para meters. Based on the same data, an intuitive flow chart was constructe d with which 129 of 157 cases could be classified (only one falsely) w ithout further statistical analysis. The five metastases with an at fi rst unknown primary could, according to the followup, all be classifie d correctly with high PP. Most ovarian carcinomas, including the mucin ous ones, can be discriminated with high probability from colonic carc inomas using a panel of three antibodies directed against CEA, cytoker atin 7, and vimentin. Copyright (C) 1998 by W.B. Saunders Company.