Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53- and p16/Rb-dependent cell cycle regulator proteins

• Published in: Pathology international 2008-12, Vol.58 (12), p.757-764
• Main Authors: Iwasa, Atsuko, Oda, Yoshinao, Kurihara, Shuichi, Ohishi, Yoshihiro, Yasunaga, Masafumi, Nishimura, Izumi, Takagi, Emi, Kobayashi, Hiroaki, Wake, Norio, Tsuneyoshi, Masazumi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA Methylation; DNA Mutational Analysis; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; malignant transformation; mature cystic teratoma; Middle Aged; Neoplasm Staging; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; p16; p53; Point Mutation; Teratoma - genetics; Teratoma - metabolism; Teratoma - pathology; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/j.1440-1827.2008.02307.x

Ovarian mature cystic teratomas (MCT) uncommonly undergo malignant transformation to squamous cell carcinoma (SCC). While alterations in the p53 tumor suppressor gene and protein have been shown, few studies have analyzed other molecular changes leading to this malignant conversion. The purpose of the present study was to investigate 21 samples of SCC arising in MCT for altered expression in known p53‐ and p16/Rb‐dependent cell cycle regulatory proteins, and the association between their expression and cellular proliferation and histological features. Overexpression of the p53 protein was observed in 14 SCC (67%), while four (19%) had point mutations in the p53 gene. Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%). Furthermore, a statistically significant correlation was observed between p53 and Rb overexpression (P = 0.0010), and the overexpression of both p53 and Rb was respectively significantly correlated with increased cellular proliferation. The results indicate that alterations in both the p53 and p16‐Rb pathways are associated with SCC arising in MCT.