Molecular Abnormalities Associated with Endocrine Tumors of the Uterine Cervix

Objective.We studied the molecular abnormalities involved in the pathogenesis of endocrine tumors of the uterine cervix. Methods.We obtained DNA from precisely microdissected archival tissue from 15 endocrine tumors of the uterine cervix, consisting of 5 carcinoids (1 typical, 4 atypical), 2 large cell neuroendocrine carcinomas, and 8 small cell carcinomas. We investigated the presence of high-risk (types 16 and 18) and intermediate-risk (types 31 and 33) human papilloma virus (HPV) sequences,TP53and K-rasgene mutations, and loss of heterozygosity (LOH) at 9 genes/chromosomal regions, including 3p14.2/FHIT,3p14–p21, 3p21, 3p22–p24, 5q21–q22/APC-MCCregion, 9p21/CDKN2,11q23/MEN1,13q/RB,and 17p/TP53. Results.HPV sequences were detected in 8 (53%) tumors, HPV 16 in 2 cases, and HPV 18 in 2 cases. LOH at 9p21 (43%) and localized 3p deletions (47%) were the most frequent allelic losses found. Allelic losses at 5q21–q22/APC-MCCregion, 11q23/MEN1,and 13q/RBwere infrequent.TP53gene mutations were detected in 7 (47%) tumors (1 atypical carcinoid and 6 carcinomas). HPV sequences were demonstrated in 4 of the 7 cases withTP53gene mutations. No K-rasmutations were detected. Conclusion.The molecular changes present in endocrine tumors of the uterine cervix have distinct features. They incorporate those present in the neuroendocrine tumors of the lung (high frequency ofTP53gene abnormalities and 9p21 deletions) with those detected in squamous cell carcinomas of the cervix (high-risk HPV sequences and localized 3p deletions).