Human Papillomavirus Type Distribution in 53 Neuroendocrine Tumors of the Cervix
O Clavero, B Lloveras, M Alejo, B Quiros, N Monfulleda, L Alemany, J Klaustermeier, W Quint, S de Sanjose, on Behalf of the RIS HPV TT Study Group. Catalan Institute of Oncology, IDIBEL, Hospitalet de Llobregat, Barcelona, Spain; Hospital del Mar, IMAS-IMIM, Barcelona, Spain; Hospital General de Hospitalet, Hospitalet de Llobregat, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; DDL Diagnostic Laboratory, Voorburg, Netherlands
Background: Neuroendocrine carcinoma of the cervix is a rare entity with a very aggressive behaviour, frequent recurrences, distant metastasis and low survival rates, with little information regarding pathogenesis. The WHO classification includes under the term on Neuroendocrine Tumours (NET): carcinoid, atypical carcinoid, large cell carcinoma and small cell carcinoma, this last one accounting for the 0.5-1% of whole cervical carcinomas. Objective: To describe the Human Papillomavirus (HPV) type distribution in NET.
Design: In the RIS HPV TT study, among 10,365 cervical carcinomas, pathologists identified 53 carcinomas with neuroendocrine features based on morphological characteristics. WHO classification was applied taking into account cell size, nuclear features and architectural pattern. To determine the neuroendocrine differentiation, immunohistochemical staining included chromogranin A (Dako), synaptophysin (clone 5438 Dako), CD 56 (clone 123c3 DAKO) and p16ink4a (Clone E6H4, CINtec® Histology Kit) was carried out. HPV detection was done through amplification of HPV DNA by SPF-10 broad-spectrum primers PCR subsequently followed by DEIA and genotyping by LiPA25 (version 1).
Results: Mean age of the patients was 48.8 y.o. Pathological classification showed 37 small cell NET, 11 large cell NET, 4 atypical carcinoid and 1 typical carcinoid. HPV detection yielded 46 HPV positive cases (86.8%) and 7 HPV negative. The types detected were HPV16 (n=22, 47.8%), HPV18 (n=20, 43.5%) and other HPV types in 4 cases (HPV35, HPV58, HPV18&52, HPV16&18&39). Overexpression of p16ink4a was observed in 86.1% of 43 cases.
Conclusions: The study confirms the association of cervical NET with high risk HPV. HPV 16 and 18 were identified in more than 90% of these tumors. We observed a four-fold increase detection of HPV18 when compared to that observed among all cervical cancer cases in this study, deserving further research.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 188, Tuesday Morning