Hepatocyte growth factor and c-Met in cervical intraepithelial neoplasia: overexpression of proteins associated with oncogenic human papillomavirus and human immunodeficiency virus.
OBJECTIVE
High prevalence of squamous cervical intraepithelial neoplasia (CIN) linked to oncogenic human papillomavirus (HPV) exits in HIV-infected women. Hepatocyte growth factor (HGF) and its receptor, c-Met, promote cell proliferation and are involved in tumor progression. Nothing is yet known about their expression in low- and high-grade CIN. Therefore, the expression, localization, and behavior of HGF and c-Met in normal and dysplastic cervical epithelium were investigated.


METHODS
We studied normal cervical mucosa from 10 healthy women, and low- and high-grade cervical lesions, uninfected (condyloma acuminata) or infected with oncogenic HPVs, from 40 HIV-negative and 48 HIV-positive women, using in situ molecular techniques, immunocytochemistry and morphoquantitative methods.


RESULTS
In 154 oncogenic HPV-infected CIN encountered in biopsy samples, the total number of epithelial cell layers increased significantly during lesion progression. This number was significantly higher in HIV-positive than in HIV-negative women for CIN1 and CIN2 (P < 0.025 to P < 0.01). In HIV-negative women, the number and percentage of HGF and c-Met immunostained cell layers, and the intensity of immunostaining were enhanced in oncogenic HPV-infected lesions as compared with normal mucosa and condyloma acuminata. The latter parameters were significantly higher in tissues of HIV-positive women (oncogenic HPV-infected CIN1 and CIN2, normal-appearing mucosa contiguous to CIN, condyloma acuminata) than in the corresponding tissues of HIV-negative women (P < 0.025 to P < 0.0001).


CONCLUSIONS
Overexpression of HGF/c-Met complex strongly correlates with oncogenic HPV and HIV infection. This overexpressed complex may stimulate cell proliferation in condyloma acuminata and participate in tumor progression in oncogenic HPV-infected lesions.
Walker
Francine
F
Department of Pathology, Institut de la Santé et de la Recherche Médicale (INSERM) Unité 410 IFR2 75870 Paris Cedex 18, France.
Kermorgant
Stéphanie
S
Daraï
Emile
E
Madelenat
Patrick
P
Cremieux
Anne Claude
AC
Hénin
Dominique
D
Lehy
Thérèse
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D002455:Cell Division; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006678:HIV / Q000378:metabolism*; D006679:HIV Seropositivity; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D027383:Papillomaviridae / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002578:Uterine Cervical Dysplasia / Q000378:metabolism*
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met