[1162] Notch1 and HPV Genotyping in Cervical Adenocarcinomas

AC Policiano, P Alves, L Martins, A Felix. Faculdade de Medicina, Lisboa, Portugal; Instituto Portugues de Oncologia, IPOLFG, Lisboa, Portugal; IPOLFG e Faculdade de Ciências Médicas, Lisboa, Portugal

Background: The link between HPV infection and cervical carcinogenesis is well established. However, additional events are needed for tumor development. Several reports suggest that Notch signaling may be involved in neoplastic transformation and it can function as a promotor or suppressor of tumor growth. It is believed that in cervical carcinomas Notch signalling might contribute to the process of tumorigenesis in association with HPV. In this study we aim to examine Notch1 and HES1 immunoexpression and to genotype HPV in a series of adenocarcinomas of the uterine cervix.
Design: Notch1C-20(receptor); Notch1EC(extracellular domain); Notch IC(intracellular domain); Notch1-S3(cleaved) and HES1(Notch1 signaling transcription target) immunoexpression was evaluated in a tissue microarray constructed with representative regions from 41 endocervical adenocarcinomas and from 6 normal endocervical specimens. Patients files were reviewed and morphological features characterized. HPV detection was done using SPF-10 broad-spectrum primers PCR, subsequently followed by DEIA and genotyping by LiPA25. Samples for both techniques were obtained from formalin fixed and paraffin embedded tissues.
Results: The Notch proteins were highly expressed in adenocarcinomas of the cervix (Table 1) in contrast to normal endocervical glands (all 6 were negative with all antibodies and had no HPV DNA).

Table 1
Notch1C20ECICS3HES1HPV(+ve)
invasive adc3719(51%)11(30%)11(30%)21(57%)19(51%)33(89%)
in situ adc42(50%)1(25%)4(100%)4(100%)4(100%)2(50%)
adc - adenocarcinoma; (+ve) - positive

An association was found between the presence of the NOTCH1-S3 and HES1 (p=0.02). No correlation was found between Notch activation and outcome or other morphological features evaluated (invasion, differentiation or metastatic behaviour).The presence of DNA HPV in carcinomas was detected in 35 cases. Multiple types were identified in a 4 cases and DNA HPV types were HPV16 (60%); 18(49%) and HPV45 (3%). No correlation was found between the presence of HPV and Notch1 immunoexpression.
Conclusions: Notch1 proteins and HES1 are highly expressed in invasive and in situ cervical adenocarcinomas indicating that Notch signaling is activated in cervical adenocarcinomas. This suggests that Notch1 may play a permissive or promoting role in cancerigenesis of cervical adenocarcinomas.
Category: Gynecologic & Obstetrics

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 186, Tuesday Morning

 

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