Cervical Carcinomas with Neuroendocrine Differentiation: A Report of 29 Cases with Immunohistochemical Analysis and Molecular Genetic Evidence of Common Clonal Origin with Coexisting Squamous and Adenocarcinomas
Robert E Emerson, Helen Michael, Mingsheng Wang, Lawrence M Roth, Liang Cheng. Indiana University School of Medicine, Indianapolis, IN
Background: Cervical neuroendocrine tumors are a rare, aggressive subtype of cervical cancer, but their immunohistochemical features and relationship to coexisting tumors are incompletely described in the medical literature. Expression of TTF1, c-kit (a potential marker or therapeutic sensitivity), and CD44 (a tumor stem cell marker) by extrapulmonary small cell carcinomas has been recently reported. Cervical neuroendocrine tumors are known to be related to high risk human papillomavirus and p16 immunohistochemical expression is expected.
Design: A search for a 22 year period was performed for all available cervical neuroendocrine tumors. Immunohistochemical staining for synaptophysin, chromogranin A, TTF1, c-kit, CD44, and p16 was performed. Loss of heterozygosity (LOH) analysis for five polymorphic microsatellite markers (D3S1300, D9S171, D11S914, D13S319, and TP53) and X chromosome inactivation analysis were performed.
Results: Twenty-nine cases were identified (17 small cell, 10 large cell, and 2 mixed). The mean patient age was 44 years (range: 18-82 years). There was coexisting adenocarcinoma in 7 cases, squamous cell carcinoma in 2 cases, adenosquamous carcinoma in 1 case, adenocarcinoma in situ in 1 case, and squamous cell carcinoma in situ in 1 case. Of 18 cases with available blocks, 13 (72%) were synaptophysin+, 8 were chromogranin A+ (44%), 9 (50%) were TTF1+, 8 (44%) were c-kit+, and 7 (39%) were CD44+. Strong patchy or strong diffuse p16 staining was seen in all cases. LOH and X chromosome inactivation analysis were performed for 17 cases, 8 of which had a coexisting squamous or adenocarcinoma component. Five of the eight (63%) cases with two components showed allelic loss in both components. All five of these cases demonstrated identical LOH between the neuroendocrine and squamous or adenocarcinoma components. Nonrandom X chromosome inactivation was seen in the neuroendocrine and other components in 4 of the 8 cases. In all 4 cases the pattern of inactivation was identical between the two components.
Conclusions: Cervical neuroendocrine carcinomas have immunophenotypic features similar to other extrapulmonary neuroendocrine carcinomas, including frequent expression of TTF1, c-kit, and CD44. Consistent staining for p16 is also seen. Concordant genetic alterations in X inactivation patterns support common clonal origin for neuroendocrine carcinomas with a coexisting squamous or adenocarcinoma component.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 134, Wednesday Morning