Protein 16 (p16CDKN2A) and transforming growth factor-beta 1 (TGF- β1) are important tumor suppressor molecules. The aim of this study was to evaluate the frequency and simultaneous expression of p16CDKN2A and TGF- β1 in cervical intraepithelial neoplasia (CIN) and cervical cancer and their relationship whit the neoplasia progression.
To evaluate the expressions of p16CDKN2A and TGF- β1 an immunohistochemical study of both proteins in 75 cervical tissues (24 CIN I, 17 CIN II, 15 CIN III and 19 squamous cell cancer) was performed.
Increased expression of epithelial and stromal p16CDKN2A in all grades of CIN and cancer was observed. Healthy controls were negative. The frequency of p16CDKN2A expression in the patients was as follow: 75% in CIN I and 100% in CIN II, CIN III and cancer. TGF- β1 expression was found increased in all patients with CIN I and CIN II and decreased in CIN III and cancer; 60% of patients with CIN III and 16% with cancer showed reactivity for TGF- β1. High intensity of p16CDKN2A reactivity and low intensity of TGF- β1 reactivity were observed.
The linear frequency of p16CDKN2A expression accompanied by decreased frequency of TGF- β1 in CIN III and cancer could be involved in the neoplasia progression.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to European Journal of Obstetrics and Gynecology and Reproductive Biology
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.Int J Cancer. 2010; 127: 2893-2917
- Expression of the p16INK4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papilloma virus infection.J Gynecol Oncol. 2008; 19: 162-168
- Natural history of cervical intraepithelial neoplasia: a critical review.Int J Gynecol Pathol. 1993; 12: 186-192
- The prognostic significance of P16, Ki-67, P63, and CK17 expression determined by immunohistochemical staining in cervical intraepithelial neoplasia 1.Korean J Obstet Gynecol. 2011; 54: 184-191
- In situ increased chemokine expression in human cervical intraepithelial neoplasia and cervical cancer.Pathol Res Pract. 2015; 211: 281-285
- Increased vascular endothelial growth factor expression, CD3 positive cell infiltration and oxidative stress in premalignant lesions of the cervix.Cancer. 2009; 115: 3680-3688
- Increased IL-2, IL-2 receptor and IL-10 positive cells in premalignant lesions of uterine cervix.Invest Clin. 2008; 49: 533-545
- Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia.World J Clin Oncol. 2014; 5: 753-763
- The importance of alpha/beta (alpha/13) interferon receptors and signaling pathways for the treatment of cervical intraepithelial neoplasias.Eur J Gynaecol Oncol. 2014; 35: 368-372
- P16 expression in cervical premalignant and malignant lesions.Exp Mol Pathol. 2006; 80: 192-196
- Living with or without cyclins and cyclin-dependent kinases.Genes Dev. 2004; 18: 2699-2711
- Efficacy of p16 and Ki-67 immunostaining in the detection of squamous intraepithelial lesions in a highrisk HPV group.Oncol let. 2016; 11: 1447-1452
- Biomarkers for cervical cancer screening: the role of p16(INK4a) to highlight transforming HPV infections.Expert Rev Proteomics. 2012; 9: 149-163
- p16INK4A overexpression in precancerous and cancerous lesions of the uterine cervix in Tunisian women.Pathol Res Pract. 2010; 206: 550-555
- Management of HPV-related cervical disease: role of p16INK4a immunochemistry. Review of the literature.Tumori. 2016; 102: 450-458
- Cytokine expression in the cervical stroma of HIV-positive and HIV-negative women with cervical intraepithelial neoplasia.Viral Immunol. 2014; 27: 350-355
- Expression of CD34, alpha-smooth muscle actin and transforming growth factor-beta1 in squamous intraepithelial lesions and squamous cell carcinoma of the cervix.J Int Med Res. 2009; 37: 446-454
- VEGF, FGF2, TGFB1 and TGFBR1 mRNA expression levels correlate with the malignant transformation of the uterine cervix.Cancer Lett. 2005; 221: 105-118
- Decreased synthesis and expression of TGF-beta1, beta2, and beta3 in epithelium of HPV 16-positive cervical precancer: a study by microdissection, quantitative RT-PCR, and immunocytochemistry.J Pathol. 2000; 192: 494-501
- TGF-beta signal transduction.Annu Rev Biochem. 1998; 67: 753-791
- Use of Avidin-Biotin-Peroxidase techniques a comparison between ABC and an unlabeled antibody (DAP) procedures.J Histochem Cytochem. 1981; 29: 577-580
- Practical issues in the application of p16 immunohistochemistry in diagnostic pathology.Hum Pathol. 2016; 51: 64-74
- HPV-16 E6/E7 promotes cell migration and invasion in cervical cancer via regulating cadherin switch in vitro and in vivo.Arch Gynecol Obstet. 2015; 292: 1345-1354
- Immunohistochemical expression of p16 and HPV L1 capsid proteins as predictive markers in cervical lesions.Arch Gynecol Obstet. 2014; 289: 1287-1292
- Roles of human papillomaviruses and p16 in oral cancer.Asian Pac J Cancer Prev. 2015; 16: 6193-6200
- p16 Expression in prostate cancer and nonmalignant lesions: novel findings and review of the literature.Appl Immunohistochem Mol Morphol. 2016; 24: 201-206
- Expression of transforming growth factor-beta 1 and -beta 2 in human papillomavirus (HPV)-associated lesions of the uterine cervix.Gynecol Oncol. 1994; 54: 349-356
- Transforming growth factor-beta in breast cancer: a working hypothesis.Breast Cancer Res Treat. 1997; 45: 81-95
- Transforming growth factor-beta and breast cancer: cell cycle arrest by transforming growth factor-beta and its disruption in cancer.Breast Cancer Res. 2000; 2: 116-124
- Deficiency of G1 regulators P53, P21Cip1 and/or pRb decreases hepatocyte sensitivity to TGFβ cell cycle arrest.BMC Cancer. 2007; 7: 215-225
- Cervical cancer cells induce apoptosis in TCD4+ lymphocytes through the secretion of TGF-β.Arch Gynecol Obstet. 2013; 287: 755-763
- HPV episome levels are potently decreased by pyrrole-imidazole polyamides.Antiviral Res. 2011; 91: 177-186
- Human papillomavirus episome stability is reduced by aphidicolin and controlled by DNA damage response pathways.J Virol. 2013; 87: 3979-3989
- Transforming growth factor beta1 promotes chromosomal instability in human papillomavirus 16 E6E7-infected cervical epithelial cells.Cancer Res. 2008; 68: 7200-7209
Published online: July 21, 2018
Accepted: July 20, 2018
Received in revised form: July 18, 2018
Received: June 1, 2018
© 2018 Elsevier B.V. All rights reserved.