WT1, monoclonal CEA, TTF1, and CA125 antibodies in the differential diagnosis of lung, breast, and ovarian adenocarcinomas in serous effusions

Abstract

The distinction between metastatic adenocarcinomas of lung (LAC), breast (BAC), and ovary (OAC) in serous effusions can be very difficult since they all can present as tight cell clusters. This is particularly challenging when the malignant effusion is the patient's initial presentation or when the patient has a history of more than one primary. The aim of this study is to evaluate the usefulness of WT1, monoclonal CEA (mCEA), TTF1, and CA125 antibodies in the differential diagnosis of metastatic adenocarcinoma from the lung, breast and ovary in serous effusions. Forty-six samples of serous effusions with their corresponding cell blocks were retrieved from our hospital computer system, including 13 BACs, 13 LACs, and 20 OACs. The diagnoses were confirmed by the surgical resection. Formalin-fixed and paraffin-embedded cell block sections were immunostained for WT1, mCEA, TTF1, and CA125. Two observers blindly reviewed the immunostained slides without knowledge of the previous clinical or histologic diagnoses. The staining intensity was graded semiquantitatively as negative, 0; weak, 1+; moderate, 2+; and strong, 3+. The percentage of positively staining cells was estimated. The distribution patterns of reactivity for WT1 and TTF1 were recorded as nuclear, and mCEA and CA125 as membranous stain. Metastatic OACs showed positive immunoreactivity to WT1 in 19/20 (95%) cases, CA125 in 20/20 (100%), and all showed negative reaction for both mCEA (0/20, 0%) and TTF1 (0/20, 0%). BAC showed positive reaction in 6/13 (46%) cases to CA125 and mCEA. Staining pattern was diffuse for CA125 and focal for mCEA. Only 2/13 (15%) were positive for WT1, while all of 13 BAC cases (0/13, 0%) were negative for TTF1. LAC showed positive immunoreactivity for TTF1 in 9/13 (69%) with a characteristic nuclear staining pattern, but only 3/13 (23%) were focally stained for WT1. In addition, 8/13 (62%) of LAC cases were positive for both CA125 and mCEA. Our results demonstrate that the WT1 stain is specific for metastatic carcinoma of ovarian primary, showing a high sensitivity. In addition, CA125 stain is very sensitive for OACs, but could be positive in about a half of LAC and BAC cases. An immunostaining pattern of positive mCEA as well as negative WT1 rules out OACs, raising the possibility of LACs and BACs. A positive TTF1 staining supports the diagnosis of metastatic carcinoma originating from lung rather than breast, while a negative TTF1 favors the diagnosis of a breast primary. Immunohistochemical studies with WT1, TTF1, and mCEA antibodies are useful in the differential diagnosis of metastatic adenocarcinomas of lung, breast, and ovary. Diagn. Cytopathol. 2007;35:370–375. © 2007 Wiley-Liss, Inc.