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Published in: Journal of Ovarian Research 1/2016

Open Access 01-12-2016 | Research

p14 expression differences in ovarian benign, borderline and malignant epithelial tumors

Authors: Vinicius Duarte Cabral, Marcelle Reesink Cerski, Ivana Trindade Sa Brito, Lucia Maria Kliemann

Published in: Journal of Ovarian Research | Issue 1/2016

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Abstract

Background

Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters.

Methods

A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher’s exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p < 0.05.

Results

p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression.

Conclusions

This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the accumulation of inactive mutant protein. The small sample size may have prevented statistically significant survival analyses and clinical correlations. Future studies should investigate genetic abnormalities in p14 coding sequences and include all types of ovarian epithelial tumors. Bigger sample sizes may be needed for significant associations.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, Fr. Int Agency Res Cancer. 2014. [cited 2016 Feb 13]. Available from: http://globocan.iarc.fr. Accessed 13 Feb 2016. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, Fr. Int Agency Res Cancer. 2014. [cited 2016 Feb 13]. Available from: http://​globocan.​iarc.​fr. Accessed 13 Feb 2016.
7.
go back to reference Cooper GM, Hausman RE. The Cell: A Molecular Approach. 6th ed. 2013. Cooper GM, Hausman RE. The Cell: A Molecular Approach. 6th ed. 2013.
9.
go back to reference Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9:701–13. Nature Publishing Group; Available from: http://dx.doi.org/10.1038/nrc2693.PubMed Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9:701–13. Nature Publishing Group; Available from: http://​dx.​doi.​org/​10.​1038/​nrc2693.PubMed
11.
go back to reference Boström J, Meyer-Puttlitz B, Wolter M, Blaschke B, Weber RG, Lichter P, et al. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. Am J Pathol. 2001;159:661–9.CrossRefPubMedPubMedCentral Boström J, Meyer-Puttlitz B, Wolter M, Blaschke B, Weber RG, Lichter P, et al. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. Am J Pathol. 2001;159:661–9.CrossRefPubMedPubMedCentral
13.
14.
go back to reference Saldanha SN, Tollefsbol TO. Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis. J Cell Physiol. 2014;229:393–406. Saldanha SN, Tollefsbol TO. Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis. J Cell Physiol. 2014;229:393–406.
15.
go back to reference Nam EJ, Kim YT. Alteration of cell-cycle regulation in epithelial ovarian cancer. Int J Gynecol Cancer. 2008;18:1169–82.CrossRefPubMed Nam EJ, Kim YT. Alteration of cell-cycle regulation in epithelial ovarian cancer. Int J Gynecol Cancer. 2008;18:1169–82.CrossRefPubMed
19.
go back to reference Machida D, Ph BD, Okayasu I, Saegusa M, Machida D, Okayasu I. Possible Associations among Expression of p14 ARF, and the Balance of Apoptosis and Cell Proliferation in Ovarian Carcinomas. Cancer. 2001;92:1177–89.CrossRef Machida D, Ph BD, Okayasu I, Saegusa M, Machida D, Okayasu I. Possible Associations among Expression of p14 ARF, and the Balance of Apoptosis and Cell Proliferation in Ovarian Carcinomas. Cancer. 2001;92:1177–89.CrossRef
21.
go back to reference Khouja MH, Baekelandt M, Nesland JM, Holm R. The clinical importance of Ki-67, p16, p14, and p57 expression in patients with advanced ovarian carcinoma. Int J Gynecol Pathol. 2007;26:418–25.CrossRefPubMed Khouja MH, Baekelandt M, Nesland JM, Holm R. The clinical importance of Ki-67, p16, p14, and p57 expression in patients with advanced ovarian carcinoma. Int J Gynecol Pathol. 2007;26:418–25.CrossRefPubMed
22.
go back to reference Havrilesky L, Darcy Kathleen M, Hamdan H, Priore RL, Leon J, Bell J, et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2003;21:3814–25.CrossRefPubMed Havrilesky L, Darcy Kathleen M, Hamdan H, Priore RL, Leon J, Bell J, et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2003;21:3814–25.CrossRefPubMed
23.
go back to reference Dong Y, Walsh MD, McGuckin MA, Gabrielli BG, Cummings MC, Wright RG, et al. Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis. Int J Cancer. 1997;74:57–63.CrossRefPubMed Dong Y, Walsh MD, McGuckin MA, Gabrielli BG, Cummings MC, Wright RG, et al. Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis. Int J Cancer. 1997;74:57–63.CrossRefPubMed
24.
go back to reference O’Neill CJ, McBride HA, Connolly LE, Deavers MT, Malpica A, McCluggage WG. High-grade ovarian serous carcinoma exhibits significantly higher p16 expression than low-grade serous carcinoma and serous borderline tumour. Histopathology. 2007;50:773–9.CrossRefPubMed O’Neill CJ, McBride HA, Connolly LE, Deavers MT, Malpica A, McCluggage WG. High-grade ovarian serous carcinoma exhibits significantly higher p16 expression than low-grade serous carcinoma and serous borderline tumour. Histopathology. 2007;50:773–9.CrossRefPubMed
29.
go back to reference Vang R, Gown AM, Farinola M, Barry TS, Wheeler DT, Yemelyanova A, et al. p16 expression in primary ovarian mucinous and endometrioid tumors and metastatic adenocarcinomas in the ovary: utility for identification of metastatic HPV-related endocervical adenocarcinomas. Am J Surg Pathol. 2007;31:653–63.CrossRefPubMed Vang R, Gown AM, Farinola M, Barry TS, Wheeler DT, Yemelyanova A, et al. p16 expression in primary ovarian mucinous and endometrioid tumors and metastatic adenocarcinomas in the ovary: utility for identification of metastatic HPV-related endocervical adenocarcinomas. Am J Surg Pathol. 2007;31:653–63.CrossRefPubMed
30.
go back to reference Kmet LM, Cook LS, Magliocco AM. A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors. Cancer. 2003;97:389–404.CrossRefPubMed Kmet LM, Cook LS, Magliocco AM. A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors. Cancer. 2003;97:389–404.CrossRefPubMed
31.
go back to reference Giurgea LN, Ungureanu C, Mihailovici MS. The immunohistochemical expression of p53 and Ki67 in ovarian epithelialborderline tumors. Correlation with clinicopathological factors. Rom J Morphol Embryol. 2012;53:967–73.PubMed Giurgea LN, Ungureanu C, Mihailovici MS. The immunohistochemical expression of p53 and Ki67 in ovarian epithelialborderline tumors. Correlation with clinicopathological factors. Rom J Morphol Embryol. 2012;53:967–73.PubMed
33.
go back to reference Li Z, Ding S, Zhong Q, Li G, Zhang Y, Chen X, et al. Significance of MMP11 and P14 ARF expressions in clinical outcomes of patients with laryngeal cancer. Int J Clin Exp Med. 2015;8:15581–90. Li Z, Ding S, Zhong Q, Li G, Zhang Y, Chen X, et al. Significance of MMP11 and P14 ARF expressions in clinical outcomes of patients with laryngeal cancer. Int J Clin Exp Med. 2015;8:15581–90.
36.
go back to reference Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB, et al. Hypermethylation-associated Inactivation of p14 ARF Is Independent of p16 INK4a Methylation and p53 Mutational Status 1. Cancer Res. 2000;60(1):129–133. Esteller M, Tortola S, Toyota M, Capella G, Peinado MA, Baylin SB, et al. Hypermethylation-associated Inactivation of p14 ARF Is Independent of p16 INK4a Methylation and p53 Mutational Status 1. Cancer Res. 2000;60(1):129–133. 
38.
go back to reference Watanabe J, Nishizaki R, Jobo T, Kamata Y, Hata H, Nishimura Y, et al. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Oncogene. 2004;23:15581–90. Elsevier Masson SAS; Available from: http://dx.doi.org/10.1111/j.0022-202X.2004.22501.x. Watanabe J, Nishizaki R, Jobo T, Kamata Y, Hata H, Nishimura Y, et al. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Oncogene. 2004;23:15581–90. Elsevier Masson SAS; Available from: http://​dx.​doi.​org/​10.​1111/​j.​0022-202X.​2004.​22501.​x.
Metadata
Title
p14 expression differences in ovarian benign, borderline and malignant epithelial tumors
Authors
Vinicius Duarte Cabral
Marcelle Reesink Cerski
Ivana Trindade Sa Brito
Lucia Maria Kliemann
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-016-0275-2

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