Origin of Peritoneal Cancer With Features of High-grade Serous Carcinoma: A Detailed Molecular Analysis

Abstract

Primary peritoneal cancer has characteristics similar to high-grade serous carcinomas of ovarian and fallopian tube origin. However, the relationship between endometriosis and primary peritoneal cancer is not well understood. This study focuses on a case of peritoneal cancer in a patient who had undergone hysterectomy and bilateral salpingo-oophorectomy 5 yr before. In addition to morphology, there was a positive for TP53 in immunohistochemistry and homologous recombination deficiency test, which were similar to high-grade serous carcinomas. However, WT1 was negative in the tumor, and extensive endometriosis coexisted. To reveal the clonal relationship between tumor and endometriosis, we dissected 3 sites each from the tumor and endometriosis and performed whole-exome sequencing analysis. As a result, we found that the tumors were of identical origin. Contrarily, no shared mutations were found in the 3 endometriosis sites. Furthermore, several shared mutations were found between the tumor and 1 endometriosis tissue, showing that the tumor and 1 ectopic endometrial gland originated from the same clone. This study indicates that several peritoneal cancers may be derived from endometriosis. We should consider the possibility of more diverse origins of peritoneal cancer than we speculated before.