p63 regulates cell growth and differentiation and contributes to tumorigenesis through its complex isoforms. Gestational trophoblastic disease encompasses a heterogeneous family of lesions with different malignant potential that arise from various trophoblast subpopulations. This study investigated the expression of p63 isoforms in various trophoblastic diseases and correlated with clinical progress, proliferation, and apoptotic activities. 4A4 and anti-p40 antibodies were applied to assess expressions of total and DeltaNp63 isoforms in 20 placentas, 62 hydatidiform moles, 9 choriocarcinomas, 5 placenta site trophoblastic tumors, and 2 epithelioid trophoblastic tumors immunohistochemically. The immunoreactivity of p63 was localized to the nuclei of cytotrophoblast, villous, and chorionic-type intermediate trophoblasts with significant correlation between 2 p63 indices (P<0.001). p63 indices were significantly lower in placentas of advanced gestational age (P<0.001). Hydatidiform moles demonstrated significantly higher p63 indices than normal placentas (P<0.001). Epithelioid trophoblastic tumors displayed the highest p63 indices (45%-80%) whereas immunoreactivity was only focal in choriocarcinoma (0%-5.62%) and was essentially absent in placenta site trophoblastic tumors. There was no significant correlation between p63 indices and subsequent development of trophoblastic neoplasia in hydatidiform moles (P>0.05). Both p63 indices positively correlated with the proliferative index (Ki67) (P<0.05), apoptotic index (M30) (P<0.005), p53 (P<0.005), and p21(WAF1/CIP1) expression (P<0.005). Our results indicate that DeltaNp63, the dominant isoforms expressed in trophoblasts, display heterogeneous expression patterns in relation to trophoblast subtypes. We also demonstrate for the first time the possible role of p63 in the pathogenesis of gestational trophoblastic disease (GTD) through its interaction with p53-dependent proliferation and apoptotic activities.
Histopathology. 2007 Oct;51(4):477-83.
AIMS: To investigate p63 expression in ovarian neoplasms. METHODS AND RESULTS: Immunohistochemistry using an antibody that detects all p63 isoforms was performed on 103 primary ovarian neoplasms of different histological types. Diffuse nuclear immunoreactivity of p63 was demonstrated in the 17 benign and five borderline Brenner tumours. Only one of the six malignant Brenner tumours displayed p63 expression. p63 immunoreactivity was absent in all the ovarian transitional cell carcinomas (TCC), but was demonstrated extensively in TCCs of the urinary bladder. Besides focal p63 expression in epidermal basal cells of immature and mature teratomas, all other ovarian lesions were devoid of p63 expression. p63 expression was also demonstrated in cervical transitional cell metaplasia and Walthard cell nests of fallopian tubes. CONCLUSIONS: Expression of p63 protein is apparently cell lineage specific and in ovarian neoplasms is confined to benign and borderline Brenner tumours. The loss of expression in malignant Benner tumours suggests a role for p63 in Brenner carcinogenesis. The distinct patterns of p63 expression in TCCs in the ovary and urinary bladder may help in their differential diagnosis.
