Increased p16 Expression in High-grade Serous and Undifferentiated Carcinoma Compared With Other Morphologic Types of Ovarian Carcinoma

There are several morphologic types of ovarian carcinoma. It has been shown that p16 is overexpressed in high-grade serous carcinoma but there has been little detailed comparison of p16 expression in the common types of ovarian carcinoma. The aim of this study was to compare p16 expression in ovarian carcinomas of serous, endometrioid, clear cell, and mucinous type with a view to ascertaining whether high expression in a primary ovarian carcinoma is specific for a serous neoplasm. We included problematic cases, which are difficult to type, such as poorly differentiated and undifferentiated carcinomas and serous carcinomas with clear cells. In these problematic groups, we compared p16 expression with that of WT1, which is known to be relatively specific for a serous phenotype. Cases of ovarian high-grade serous carcinoma (n=38), endometrioid carcinoma (n=15), clear cell carcinoma (n=12), and mucinous carcinoma (n=10) were stained with p16. Cases were scored both with respect to distribution of immunoreactivity (0-5) and intensity (0-3). An immunohistochemical composite score was also calculated (0-15) by multiplying the distribution and intensity scores. Serous carcinomas typically exhibited high p16 expression; there was statistically significant higher p16 expression in serous carcinomas compared with the other morphologic types. There was high p16 and WT1 expression in most undifferentiated carcinomas and in serous carcinomas with clear cells, suggesting that these represent variants of serous carcinoma. We have demonstrated that p16 is highly expressed in high-grade serous and undifferentiated carcinomas compared with other morphologic types of ovarian carcinoma. This may be useful, in conjunction with WT1, in the classification of problematic neoplasms. p16 may be involved in the pathogenesis of high-grade ovarian serous carcinomas, possibly through inactivation of retinoblastoma protein.