Insulin-like growth factor II mRNA binding protein 3 (IMP3) expression in cervical intraepithelial neoplasia and its relationship with HIV-infection status
Alessandro Del Gobbo A E , Emanuela Bonoldi B , Fulvia Milena Cribiù A , Ilaria Franceschetti C , Caterina Matinato D , Stefano Fiori A , Umberto Gianelli A and Silvano Bosari AA Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan Medical School, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20100 Milan, Italy.
B Division of Pathology, Ospedale ‘A. Manzoni’, Via dell’Eremo 9/11, 23900, Lecco, Italy.
C Division of Pathology, Ospedale San Bortolo, Viale Ferdinando Rodolfi 37, 36100, Vicenza, Italy.
D Laboratory of Microbiology, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Via Francesco Sforza, 35, 20100 Milan, Italy.
E Corresponding author. Email: alessandro.delgobbo@policlinico.mi.it
Sexual Health 12(1) 22-26 https://doi.org/10.1071/SH13144
Submitted: 17 September 2013 Accepted: 10 October 2014 Published: 27 November 2014
Abstract
Background: Cervical cancer is preventable through screening, and HIV treatment guidelines recommend that all HIV-infected women receive cervical cancer twice during the year after HIV diagnosis and annually thereafter. Different immunohistochemical markers have been studied to highlight cervical intraepithelial lesions of low and high grade, the most widely used being p16. Recent studies have shown that insulin-like growth factor mRNA binding protein 3 (IMP3) plays a role in the development of invasive squamous cell carcinoma from cervical dysplasia, both in histology and in liquid-based cytology. Methods: We evaluated the clinical significance of the immunohistochemical expression of IMP3 and p16 in histological samples of cervical intraepithelial neoplasia from 56 samples of HIV-positive and 30 samples of HIV-negative patients. Results: A significant difference was found in IMP3 and p16 protein expression between HIV-positive and HIV-negative specimens. All cases of HIV-positive low grade squamous intraepithelial neoplasia (L-SIL) with IMP3 expression progressed in high grade (H)-SIL. However, the HIV-positive patients with IMP3-negative L-SIL remained stable or had a negative follow up. The L-SIL of HIV-negative patients with IMP3 protein expression had an uneventful follow up. IMP3-positive H-SIL recurred with low- or high-grade dysplasia during follow up after conisation in both populations. All IMP3-negative L-SIL and H-SIL had negative pap tests at follow up. Conclusions: In HIV-positive cases, IMP3 showed a higher sensitivity than p16 in identifying patients at risk of progression and recurrence.
Additional keywords: cervical intraepithelial neoplasm, HPV infection, p16.
References
[1] Armstrong EP. Prophylaxis of cervical cancer and related cervical disease: a review of the cost-effectiveness of vaccination against oncogenic HPV types. J Manag Care Pharm 2010; 16 217–30.| 20331326PubMed |
[2] World Health Organization. Fact sheet no. 297: Cancer. 2006. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/index.html [verified 2 January 2013].
[3] Globocan. Factsheets. 2008. Available from: http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900#WOMEN [verified 2 January 2013].
[4] Centers for Disease Control and Prevention. HIV in the United States: at a glance. Atlanta: Centers for Disease Control and Prevention; 2012. Available from: http://www.cdc.gov/hiv/topics/women/index.htm [verified 2 January 2013].
[5] Roccio M, Dal Bello B, Gardella B, Carrara M, Gulminetti R, Mariani B, et al HPV infection and intraepithelial lesions: comparison between HIV positive and negative women. Curr HIV Res 2012; 10 614–9.
| 1:CAS:528:DC%2BC38Xhs1ygs7%2FP&md5=3eb162a678f88069c054f72f1b2f1389CAS | 22934657PubMed |
[6] Spitzer M. Lower genital tract intraepithelial neoplasia in HIV-infected women: guidelines for evaluation and management. Obstet Gynecol Surv 1999; 54 131–7.
| Lower genital tract intraepithelial neoplasia in HIV-infected women: guidelines for evaluation and management.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1M7jsFWltg%3D%3D&md5=7f25dbeaae4e6d8b26ebf25d4c0835dcCAS | 9950005PubMed |
[7] Kurman RJ, Henson DE, Herbst AL, Noller KL, Schiffman MH. Interim guidelines for management of abnormal cervical cytology. 1992 National Cancer Institute Workshop. JAMA 1994; 271 1866–9.
| Interim guidelines for management of abnormal cervical cytology. 1992 National Cancer Institute Workshop.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c3lsVWquw%3D%3D&md5=67f637c6cead99e27302eee69ffd720eCAS | 8196145PubMed |
[8] Agoff SN, Lin P, Morihara J, Mao C, Kiviat NB, Koutsky LA. p16(INK4a) expression correlates with degree of cervical neoplasia: a comparison with Ki-67 expression and detection of high-risk HPV types. Mod Pathol 2003; 16 665–73.
| p16(INK4a) expression correlates with degree of cervical neoplasia: a comparison with Ki-67 expression and detection of high-risk HPV types.Crossref | GoogleScholarGoogle Scholar | 12861062PubMed |
[9] Nicol AF, Golub JE, De Silva JR, Cunha CB, Amaro-Filho SM, Oliveira NS, Menezes W, Viana Andrade C, Russomano F, Tristão A, Grinsztejn B, Khalili Friedman R, Oliveira MP, Pires A, Nuovo GJ. An evaluation of p16(INK4a) expression in cervical intraepithelial neoplasia specimens, including women with HIV-1. Mem Inst Oswaldo Cruz 2012; 107 571–7.
| An evaluation of p16(INK4a) expression in cervical intraepithelial neoplasia specimens, including women with HIV-1.Crossref | GoogleScholarGoogle Scholar | 22850945PubMed |
[10] Köbel M, Xu H, Bourne PA, Spaulding BO, Shih IeM, Mao TL, Soslow RA, Ewanowich CA, Kalloger SE, Mehl E, Lee C-H, Huntsman D, Gilks CB. IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype. Mod Pathol 2009; 22 469–75.
| IGF2BP3 (IMP3) expression is a marker of unfavorable prognosis in ovarian carcinoma of clear cell subtype.Crossref | GoogleScholarGoogle Scholar | 19136932PubMed |
[11] Findeis-Hosey JJ, Xu H. Insulin-like growth factor II-messenger RNA-binding protein-3 and lung cancer. Biotech Histochem 2012; 87 24–9.
| Insulin-like growth factor II-messenger RNA-binding protein-3 and lung cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhs1CitbrM&md5=497b524c08c40affde32cee331bd4a8aCAS | 21838610PubMed |
[12] Noske A, Faggad A, Wirtz R, Darb-Esfahani S, Sehouli J, Sinn B, Nielsen FC, Weichert W, Buckendah A-C, Röske A, Müller B, Dietel M, Denkert C. IMP3 expression in human ovarian cancer is associated with improved survival. Int J Gynecol Pathol 2009; 28 203–10.
| IMP3 expression in human ovarian cancer is associated with improved survival.Crossref | GoogleScholarGoogle Scholar | 19620937PubMed |
[13] Lu D, Yang X, Jiang NY, Woda BA, Liu Q, Dresser K, Mercurio AM, Rock KL, Jiang Z. IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer. Am J Surg Pathol 2011; 35 1638–45.
| IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer.Crossref | GoogleScholarGoogle Scholar | 21997684PubMed |
[14] Li C, Rock KL, Woda BL, Jiang Z, Fraire AE, Dresser K. IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16INK4a expression. Mod Pathol 2007; 20 242–7.
| IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an immunohistochemical study in comparison with p16INK4a expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXivVSltr4%3D&md5=653b2a82cc3bef1c7bab76d57492d29fCAS | 17192788PubMed |
[15] Vercellini P, Cribiù FM, Del Gobbo A, Carcangiu ML, Somigliana E, Bosari S. The oncofetal protein IMP3: a novel biomarker and triage tool for premalignant atypical endometriotic lesions. Fertil Steril 2013; 99 1974–9.
| The oncofetal protein IMP3: a novel biomarker and triage tool for premalignant atypical endometriotic lesions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXktlGmur8%3D&md5=28b42a1edeb44ff18013a1dd46915e3aCAS | 23473990PubMed |
[16] Wei Q, Fu B, Liu J, Xu J, Zhao T. Combined detection of p16(INK4a) and IMP3 increase the concordance rate between cervical cytologic and histologic diagnosis. Int J Clin Exp Pathol 2013; 15 1549–57.
[17] Strickler HD, Fazzari M, Kovacs A, Isasi C, Napolitano LA, Minkoff H, Gange S, Young M, Sharp GB, Kaplan RC, Cohen M, Gunter MJ, Harris TG, Yu H, Schoenbaum E, Landay AL, Anastos K. Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women. J Infect Dis 2008; 197 319–27.
| Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXitlaktr0%3D&md5=78039af9158cd0ebffba003ea64ae179CAS | 18177247PubMed |
[18] Kirby TO, Allen ME, Alvarez RD, Hoesley CJ, Huh WK. High-risk human papillomavirus and cervical intraepithelial neoplasia at time of atypical squamous cells of undetermined significance cytologic results in a population with human immunodeficiency virus. J Low Genit Tract Dis 2004; 8 298–303.
| High-risk human papillomavirus and cervical intraepithelial neoplasia at time of atypical squamous cells of undetermined significance cytologic results in a population with human immunodeficiency virus.Crossref | GoogleScholarGoogle Scholar | 15874876PubMed |