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Array-Comparative Genomic Hybridization Analysis of Primary Endometrial and Ovarian High-grade Neuroendocrine Carcinoma Associated With Adenocarcinoma: Mystery Resolved?

Mhawech-Fauceglia, Paulette M.D.; Odunsi, Kunle M.D., Ph.D.; Dim, Daniel M.D.; Nowak, Norma M.D.; Lele, Shashikant M.D.; Cheney, Richard T. M.D.; Pejovic, Tanja M.D., Ph.D.

International Journal of Gynecological Pathology: October 2008 - Volume 27 - Issue 4 - p 539-546
doi: 10.1097/PGP.0b013e31816bcda4

High-grade neuroendocrine carcinomas (NECs) of the uterine corpus and ovary are very rare tumors, and whenever diagnosed, they are usually associated with epithelial carcinoma. Because of their rarity, the molecular characteristics of these tumors are still unknown. To shed some light, we studied the genetic abnormalities of each of the 2 components, NEC and adenocarcinoma, in 4 cases arising in the ovary and the uterine corpus using array-comparative genomic hybridization. Both components of all 4 cases showed almost similar genetic abnormalities. Genetic alterations exclusively seen in adenocarcinomas included losses of 2p21.1, 10q, 12q, 9p23, gains on 2p, 3p, 3q, 4p, 5q, 6q, 10p, 15q, and amplification of 6q22.31. However, the NEC component showed numerous additional genetic abnormalities in comparison with the adenocarcinomas including gain on 6p25.3-p21.2 and 19q12 and losses on 6q24.2-q27, 19q13.11-13.2, and 19q13.31-13.41, where numerous genes involved in the pathogenesis of epithelial ovarian carcinoma have been previously identified. Our data indicate that NEC and adenocarcinomas are, in most part, genetically similar tumors and might indeed have a common origin. However, the NEC components exhibited more genetic abnormalities in comparison with the adenocarcinoma, suggesting that when the NEC clones become more dedifferentiated, they acquire additional genetic abnormalities. Because of the limited cases analyzed, a larger study is still needed to confirm our observation.

Departments of Pathology and Laboratory Medicine (P.M.F., D.D., N.N., R.T.C.)

Gynecology-Oncologic Surgery (K.O., S.L.), Roswell Park Cancer Institute, Buffalo, New York

Division of Gynecologic Oncology at Oregon Health & Science University (T.P.), Portland, Oregon

Address correspondence and reprint requests to Paulette Mhawech-Fauceglia, MD, Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton St, Buffalo, NY 14263. E-mail:;

©2008International Society of Gynecological Pathologists