Molecular abnormalities associated with endocrine tumors of the uterine cervix

Objective. We studied the molecular abnormalities involved in the pathogene sis 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 t ypical, 4 atypical), 2 large cell neuroendocrine carcinomas, and 8 small ce ll carcinomas. We investigated the presence of high-risk (types 16 and 18) and intermediate-risk (types 31 and 33) human papilloma virus (HPV) sequenc es, TP53 and K-ras gene mutations, and loss of heterozygosity (LOH) at 9 ge nes/chromosomal regions, including 3p14.2/FHIT, 3p14-p21, 3p21, 3p22-p24, 5 q21-q22/APC-MCC region, 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%) w ere the most frequent allelic losses found. Allelic losses at 5q21-q22/APC- MCC region, 11q23/MEN1, and 13q/RB were infrequent. TP53 gene mutations wer e detected in 7 (47%) tumors (1 atypical carcinoid and 6 carcinomas). HPV s equences were demonstrated in 4 of the 7 cases with TP53 gene mutations. No K-ras mutations were detected. Conclusion. The molecular changes present in endocrine tumors of the uterin e cervix have distinct features. They incorporate those present in the neur oendocrine tumors of the lung (high frequency of TP53 gene abnormalities an d 9p21 deletions) with those detected in squamous cell carcinomas of the ce rvix (high-risk HPV sequences and localized 3p deletions). (C) 1999 Academi c Press.