Immunophenotypic analysis in early Müllerian serous carcinogenesis

Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16^Ink4a, estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16^Ink4a immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16^Ink4a and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16^Ink4a was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16^Ink4a has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16^Ink4a immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.