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p16INK4A overexpression and HPV infection in uterine cervix adenocarcinoma

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Abstract

Human papillomaviruses (HPVs) are causally involved in the genesis of cervical carcinomas and their precursors, and there is a strong relationship between the cyclin-dependant kinase inhibitor p16INK4A and HPV infection. This study was carried out to assess the correlations between p16INK4A expression as an early biomarker of the endocervical adenocarcinoma and HPV infection. p16INK4A expression and HPV typing were performed on 46 samples including 5 normal endocervix, 9 benign lesions of the endocervix, 25 endocervical adenocarcinomas, and 7 endometrioid adenocarcinomas of the uterine corpus. A semiquantification of the p16INK4A immunostaining was realized (using both the staining intensity and the percentage of positive cells) and was graded from 0 to 15. All of the 25 endocervical adenocarcinomas overexpressed p16INK4A; the adjacent epithelium and the connective tissue were strictly negative. No p16INK4A was detected in nine benign endocervical lesions and in five normal endocervix. Few endometrioid adenocarcinomas of the uterine corpus that infiltrate the endocervix exhibited a low immunoreactivity (score 0/15 or 1/15). This pattern of expression is significantly associated with HPV infection (p<10−3), mainly high-risk HPV types (p=0.02). Our results suggest that p16INK4A is a putative molecular biomarker that consistently discriminates uterine cervix adenocarcinomas from benign lesions and from endometrioid adenocarcinomas of the uterine corpus .

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Acknowledgements

We thank Mrs. Intissar Klibi-Toumi and Catherine Gadois for her technical assistance and Dr. Bernard Fontanière and Mrs. Evelyn Bayle for reviewing the manuscript.

Nabiha Missaoui is a recipient of a fellowship from l’Agence Universitaire de la Francophonie (AUF). This work was supported bye the Ligue contre le Cancer, Comité de la Loire.

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Authors and Affiliations

  1. Anatomie Pathologique, Bat 10, Hôpital Edouard Herriot, 69437, Lyon, Cedex 03, France

    Nabiha Missaoui, Lucien Frappart & Cheick Traore

  2. Anatomie Pathologique, CHU Farhet Hached, rue du Docteur Moreau, BP176, 4000, Sousse, Tunisie

    Sihem Hmissa, Amel Trabelsi, Atef Ben Abdelkader, Moncef Mokni, Mohamed Tahar Yaacoubi & Sadok Korbi

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  1. Nabiha Missaoui
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Correspondence to Nabiha Missaoui.

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Missaoui, N., Hmissa, S., Frappart, L. et al. p16INK4A overexpression and HPV infection in uterine cervix adenocarcinoma. Virchows Arch 448, 597–603 (2006). https://doi.org/10.1007/s00428-005-0141-x

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  • DOI: https://doi.org/10.1007/s00428-005-0141-x

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