**2.2 Immunophenotypic features of ovarian high-grade serous carcinomas**

Immunohistochemical analysis should be performed in order to distinguish ovarian high-grade serous carcinoma from mesothelioma or other poorly differentiated carcinomas in cases of peritoneal carcinomatosis. It can also be useful in small biopsies and in post-therapy specimens.

Both classical and SET HGSC histotypes show positive immunoreactivity against CK7, p16, PAX8, WT1, ER (oestrogen receptor) and PgR (progesterone receptor), and this panel of antibodies is enough to establish an ovarian serous carcinoma diagnosis [5]. In addition, 30–50% of HGSCs can exhibit three different aberrant expression patterns for p53, strong, diffuse nuclear overexpression in >80% of cells associated with TP53 missense mutation, no expression implying p53 loss of function and diffuse cytoplasmic expression with weak nuclear intensity similar to wild-type immunoreactivity correlated with loss of function mutations disrupting the nuclear localization signal domain [28, 29]. Strong positive p53 immunoreactivity can also help to identify foci of intraepithelial carcinoma on the ovarian surface or in the fallopian tube epithelium (STIC). HGSCs also exhibit cytoplasmic and/or nuclear p16 expression along with a high Ki-67 (MIB-1) cell proliferation index (>75%) [30].

Ovarian HGSCs can be differentiated from mesotheliomas using a panel of various antibodies such as PAX8, Ber-EP4, MOC-31, ER (positive expression in ovarian serous carcinomas) and Calretinin, CK5/6 (both positive in mesotheliomas) [31].

Diagnostic problem can arise between HGSC of solid morphologic patterns and a poorly differentiated endometrioid carcinoma. In such a case serous carcinoma displays diffuse strong staining for WT1, p53 and p16 [32, 33].

Serous carcinoma of the endometrium shows negative or focally weakly positive WT1 immunoreactivity but p53 positive, therefore, metastatic serous carcinoma with this immunophenotype should be considered endometrial than ovarian origin [33].

WT1 immunopositivity is also observed in serous borderline tumours and in sex cordstromal tumours [34, 35]. On the other hand, serous borderline and benign tumours show negative immunoreactivity for p53 [29, 33].
