P16 Expression in Early Müllerian Serous Carcinogenesis
Houman Nafisi, Zeina Ghorab, Nadia Ismiil, Reda Saad, Valerie Dube, Mahmoud A Khalifa, Sharon Nofech-Mozes. University of Toronto, Toronto, Canada; Sunnybrook Health Sciences Centre, Toronto, Canada
Background: Mutation of tumor suppressor gene p53 is believed to be responsible for the initiation and progression of serous endometrial (ESC) and ovarian (OSC) carcinomas as well as their early/localized forms: endometrial intraepithelial carcinoma (EIC), tubal intraepithelial carcinoma (TIC) and the putative precursor p53 signature (p53S). In the majority of cases, p53 mutation is associated with p53 immunoreactivity; however, some molecular events do not result in p53 protein accumulation. Recent studies demonstrated P16 expression in ESC and OSC but data on its expression in early serous carcinogenesis is limited. We aimed to examine p16 immunoreactivity in EIC, TIC and p53S.
Design: We studied p53 and p16 expression in EIC (n=27; 9 pure EIC and 18 with adjacent ESC), TIC (n=10) and p53S cases (n=11), using immunohistochemistry. Expression [percent staining (score 0-4) + intensity (score 1-3)] was assessed in the neoplastic epithelium and categorized as positive if the combined score was ≥5.
Results: Among EIC cases, 22/27 (81%) were positive for p53 and 27/27 (100%) for p16. Among ESC cases 14/18 (78%) were positive for p53 and (17/18) 94% for p16. Among TIC cases, 9/10 (90%) were p53 positive and 10/10 (100%) were p16 positive. P53 was negative in 4 cases on both EIC and ESC components, one pure EIC and one TIC case. All p53 negative cases had typical morphologic features of serous/intraepithelial carcinoma. P53 was positive in all 11 p53S by definition, while p16 was universally negative.
Conclusions: We analyzed the gene products of p53 and p16 with pivotal role in cell cycle regulation and tumorigenesis. There is a high level of concordance between p53 and p16 expression in ESC and EIC component. These results suggest that p16 has a role in early müllerian serous carcinogenesis but is absent in non-committed lesions such as p53 signature. P16 immunohistochemistry is more sensitive than p53 in identifying early/localized forms of serous carcinoma and can be used as an adjunct confirmatory tool in p53 negative cases.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 193, Tuesday Morning