CC BY-NC-ND 4.0 · Rev Bras Ginecol Obstet 2017; 39(01): 21-25
DOI: 10.1055/s-0037-1598042
Original Article
Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil

Immunohistochemical Expression of the Tumor Suppressor Protein p16INK4a in Cervical Adenocarcinoma

Expressão imunhistoquímica da proteína de supressão tumoral p16INK4a em adenocarcinoma cervical
José Eleutério Jr
1   Department of Pathology, Faculty of Medicine, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil
,
Thiago Silva Lima
1   Department of Pathology, Faculty of Medicine, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil
,
Maria do Perpétuo Socorro Cunha
2   Department of Surgical Pathology, Instituto do Câncer do Ceará, Fortaleza, CE, Brazil
,
Diane Isabelle Magno Cavalcante
1   Department of Pathology, Faculty of Medicine, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil
,
Angélica Maria Holanda Silva
1   Department of Pathology, Faculty of Medicine, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil
› Author Affiliations
Further Information

Publication History

02 May 2016

23 November 2016

Publication Date:
28 February 2017 (online)

Abstract

Objective To evaluate the diagnostic utility of the p16ink4a protein expression as a marker for adenocarcinoma of the cervix.

Methods In a cross-sectional study, p16ink4a expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16ink4a was evaluated using a conventional contingency table, and the Kappa (κ) index was used to evaluate the agreement of the marker with the tissue diagnosis.

Results In total, 66% of the invasive adenocarcinoma cases were positive for p16ink4a. All of the adenomatous polyps cases used as negative controls were shown to be negative for p16ink4a. The marker showed a high sensitivity and a high negative predictive value. The Kappa index was good for p16ink4a (κ = 0.6).

Conclusion Considering the strong association between the p16ink4a marker and the cervical adenocarcinoma, its use represents an important tool for reducing incorrect diagnoses of adenocarcinoma and thereby avoiding overtreatment.

Resumo

Objetivo Avaliar a utilidade diagnóstica da expressão da proteína p16ink4a como marcador de adenocarcinoma do colo.

Métodos Em estudo transversal, a expressão de p16ink4a foi avaliada em 30 biópsias cervicais de pacientes diagnosticadas com adenocarcinoma invasivo de colo uterino provenientes de dois serviços de referência no Brasil, comparando com achados em 18 biópsias de pólipos endocervicais (grupo de controle). Para avaliar a performance do teste, foi utilizada tabela de contingência convencional, e para avaliar a concordância com o diagnóstico, foi aplicado o índice de Kappa (κ).

Resultados No total, 66% dos casos de adenocarcinoma invasivo foram positivos para p16ink4a. Todos os pólipos adenomatosos foram negativos para p16ink4a. O marcador mostrou uma alta sensibilidade e alto valor preditivo negativo. O índice de Kappa foi bom para p16ink4a (κ = 0.6).

Conclusion Considerando a forte associação entre o marcador p16ink4a e o adenocarcinoma cervical, seu uso representa uma ferramenta importante para reduzir o risco de diagnóstico incorreto de adenocarcinoma e, por conseguinte, evitar o excesso de tratamentos.

 
  • References

  • 1 Capote Negrin LG. Epidemiology of cervical cancer in Latin America. Ecancermedicalscience 2015; 9: 577
  • 2 Brasil. Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) [Internet]. [Estimate 2012: incidence of cancer in Brazil]. Rio de Janeiro: INCA; 2011 [cited 2016 Mar 15]. Available from: http://portal.saude.sp.gov.br/resources/ses/perfil/gestor/homepage/estimativas-de-incidencia-de-cancer-2012/estimativas_incidencia_cancer_2012.pdf . Portuguese.
  • 3 Dahlström LA, Ylitalo N, Sundström K. , et al. Prospective study of human papillomavirus and risk of cervical adenocarcinoma. Int J Cancer 2010; 127 (08) 1923-1930
  • 4 Silverberg SG, Ioffe OB. Pathology of cervical cancer. Cancer J 2003; 9 (05) 335-347
  • 5 Young RH, Clement PB. Endocervical adenocarcinoma and its variants: their morphology and differential diagnosis. Histopathology 2002; 41 (03) 185-207
  • 6 Termini L, Villa LL. [Biomarkers in cervical cancer screening]. J Bras Doenças Sex Transm 2008; 20 (02) 125-131 Portuguese
  • 7 Rosa MI, Medeiros LR, Rosa DD, Bozzeti MC, Silva FR, Silva BR. [Human papillomavirus and cervical neoplasia]. Cad Saude Publica 2009; 25 (05) 953-964 Portuguese.
  • 8 McCluggage WG. Immunohistochemical and functional biomarkers of value in female genital tract lesions. Int J Gynecol Pathol 2006; 25 (02) 101-120
  • 9 Cameron RI, Maxwell P, Jenkins D, McCluggage WG. Immunohistochemical staining with MIB1, bcl2 and p16 assists in the distinction of cervical glandular intraepithelial neoplasia from tubo-endometrial metaplasia, endometriosis and microglandular hyperplasia. Histopathology 2002; 41 (04) 313-321
  • 10 Abu Backer FM, Nik Mustapha NR, Othman NH. Clinicopathological comparison of adenocarcinoma of cervix and endometrium using cell cycle markers: P16ink4a, P21waf1, and p27Kip1 on 132 cancers. Infect Dis Obstet Gynecol 2011; 2011: 857851
  • 11 Wang JL, Zheng BY, Li XD, Angström T, Lindström MS, Wallin KL. Predictive significance of the alterations of p16INK4A, p14ARF, p53, and proliferating cell nuclear antigen expression in the progression of cervical cancer. Clin Cancer Res 2004; 10 (07) 2407-2414
  • 12 Yanaranop M, Ayuwat S, Nakrangsee S. Differential diagnosis between primary endocervical and endometrial adenocarcinoma using immunohistochemical staining of estrogen receptor, vimentin, carcinoembryonic antigen and p16. J Med Assoc Thai 2016; 99 (Suppl. 02) S106-S115
  • 13 Eleutério Jr J, Giraldo PC, Gonçalves AKS. , et al. Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4a and high-risk human papillomavirus. Acta Obstet Gynecol Scand 2007; 86 (01) 94-98
  • 14 Kong CS, Balzer BL, Troxell ML, Patterson BK, Longacre TA. p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia. Am J Surg Pathol 2007; 31 (01) 33-43
  • 15 Pecorelli S, Zigliani L, Odicino F. Revised FIGO staging for carcinoma of the cervix. Int J Gynaecol Obstet 2009; 105 (02) 107-108
  • 16 Schorge JO, Lea JS, Elias KJ. , et al. P16 as a molecular biomarker of cervical adenocarcinoma. Am J Obstet Gynecol 2004; 190 (03) 668-673
  • 17 Caponio MA, Addati T, Popescu O. , et al. P16(INK4a) protein expression in endocervical, endometrial and metastatic adenocarcinomas of extra-uterine origin: diagnostic and clinical considerations. Cancer Biomark 2014; 14 (02/03): 169-175
  • 18 Pinto AP, Degen M, Villa LL, Cibas ES. Immunomarkers in gynecologic cytology: the search for the ideal ‘biomolecular Papanicolaou test’. Acta Cytol 2012; 56 (02) 109-121
  • 19 Alfsen GC, Thoresen SO, Kristensen GB, Skovlund E, Abeler VM. Histopathologic subtyping of cervical adenocarcinoma reveals increasing incidence rates of endometrioid tumors in all age groups: a population based study with review of all nonsquamous cervical carcinomas in Norway from 1966 to 1970, 1976 to 1980, and 1986 to 1990. Cancer 2000; 89 (06) 1291-1299
  • 20 Li C, Rock KL, Woda BA, 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 p16(INK4a) expression. Mod Pathol 2007; 20 (02) 242-247
  • 21 Riethdorf L, Riethdorf S, Lee KR, Cviko A, Löning T, Crum CP. Human papillomaviruses, expression of p16, and early endocervical glandular neoplasia. Hum Pathol 2002; 33 (09) 899-904
  • 22 Anghebem-Oliveira MI, Merlin JC. [Is the p16 protein a new marker for neoplastic progression in the cervix?]. Rev Bras Anal Clín. 2010; 42 (03) 181-185 Portuguese.
  • 23 Yonamine PTK, Junqueira MSG, Rodrigues JO. , et al. [Association between p16 expression and cervical intraepithelial neoplasia]. Arq Ciênc Saúde. 2009; 16 (04) 161-165 Portuguese.