FAT1 is differentially expressed in cancers affecting the serosal cavities

Introduction: FAT1 is mutated in many types of cancer. The objective of this study was to analyze the diagnostic role of FAT1 protein in cancers affecting the serosal cavities. Methods: FAT1 protein expression by immunohistochemistry was analyzed in 256 effusions (139 peritoneal, 116 pleural, 1 pericardial), consisting of 96 tubo-ovarian carcinomas, 56 breast carcinomas, 44 mesotheliomas, 28 uterine corpus and cervical carcinomas, 15 lung carcinomas, 13 gastrointestinal carcinomas and 4 cancers of other origin. Results: FAT1 expression was most common in gastrointestinal carcinomas (12/13; 92%), followed by lung (9/15; 60%), breast (31/56; 55%) and uterine cervical (4/8; 50%) carcinomas, with infrequent expression in other tumors, including tubo-ovarian carcinomas (5/96; 5%). Mesotheliomas were uniformly negative. Staining of a limited series of surgical specimens showed comparable results for patient-matched breast carcinomas (29/41; 71%), whereas tubo-ovarian carcinomas were more frequently positive (16/57; 28%), though often focally, compared to effusions. Eight epithelioid mesotheliomas were negative (0/8; 0%). Survival analysis for 42 breast carcinoma patients with effusion for whom clinical data were available showed no association with overall (p=0.398) or disease-free (p=0.255) survival. Conclusion: FAT1 is commonly expressed in carcinomas of gastrointestinal, lung or breast origin, but is rarely expressed in tubo-ovarian carcinoma effusions and is absent in mesothelioma. Whether this difference is of use in the diagnostic setting remains to be established.