Guanylyl cyclase C is a specific marker for differentiating primary and metastatic ovarian mucinous neoplasms

Distinguishing primary ovarian mucinous neoplasms from metastatic mucinous adenocarcinomas with ovarian involvement can be difficult, especially when characteristic gross and microscopic features are not present. CK7/CK20 expression appears to be more useful for distinguishing metastatic gastrointestinal adenocarcinomas from the lower tract. The addition of CDX2 for distinguishing metastatic upper gastrointestinal tract adenocarcinomas from primary ovarian mucinous neoplasms offers little advantage over CK7/CK20 coordinate expression. Guanylyl cyclase C (GCC) is a brush border membrane receptor for the endogenous peptides guanylin and uroguanylin, and the homologous diarrheagenic bacterial heat-stable enterotoxins that is selectively expressed by epithelial cells from the duodenum to the rectum, but not by normal epithelia of the stomach or esophagus, or normal extramucosal cells in humans. We studied 50 ovarian tumors: 27 primary ovarian mucinous neoplasms (7 cystadenomas, 10 borderline tumors, and 10 cystadenocarcinomas) and 23 metastatic mucinous adenocarcinomas with ovarian involvement (13 colorectal adenocarcinomas, 4 gastric adenocarcinomas, 6 appendiceal mucinous tumors (4 adenocarcinomas, 1 with neuroendocrine features, and 2 appendiceal mucinous cystadenomas). For primary ovarian mucinous neoplasms, 25 of 27 were negative for GCC. Twelve of thirteen cases of colorectal adenocarcinoma (except for 1 neuroendocrine adenocarcinoma) were positive for GCC. Three of four appendiceal mucinous adenocarcinomas were positive for GCC in both the primary and metastatic tumors (except for 1 neuroendocrine adenocarcinoma). Two of two appendiceal mucinous cystadenomas were positive for GCC. Of four cases of gastric adenocarcinoma with ovarian involvement, only one (primary tumor) exhibited focal GCC staining. These findings suggest GCC may be a useful marker for differentiating primary and secondary ovarian mucinous neoplasms.