Nuclear co-expression of p14^ARF and p16^INK4A in uterine cervical cancer-derived cell lines containing HPV

Article type: Research Article

Authors: Vázquez-Vega, Salvador^a | Sánchez-Suárez, Lilia Patricia^b | Contreras-Paredes, Adriana^d | Castellanos-Juárez, Emilio^b | Peñarroja-Flores, Rubicelia^b | Lizano-Soberón, Marcela^{c; d} | Andrade-Cruz, Rafael^a | García-Carrancá, Alejandro^{c; d} | Benítez-Bribiesca, Luis^{b; *}

Affiliations: [a] Department of Pathology, Hospital of Gynecology and Pediatrics 3A, Instituto Mexicano del Seguro Social, Delegación Norte, Mexico, D.F., Mexico | [b] Medical Oncological Research Unit, Oncology Hospital, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico, D.F., Mexico | [c] Institute of Biomedical Research, Universidad Nacional Autónoma de México, Mexico, D.F., Mexico | [d] National Cancer Institute, Secretaría de Salud, Mexico, D.F., Mexico

Correspondence: [*] Corresponding author: Dr. Luis Benítez-Bribiesca, Medical Oncological Research Unit, Oncology Hospital, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico, D.F., Mexico. Tel.: +52 55 55786174; E-mail: [email protected].

Abstract: The Papanicolaou test (Pap) has been responsible for a significant reduction of cervical cancer-related morbimortality. In order to increase its sensitivity and specificity new markers have been studied and incorporated to cytological and histological methods for diagnosis for cervical cancer, such as p16INK4A that has been considered the immunocytochemical marker of choice for detection of HPV related cancers. We considered that p14ARF could be a complementary marker in order to improve the accuracy of cytological diagnosis because its genetic proximity to p16INK4A. We performed a systematic analysis of several putative cervical cancer markers in order to evaluate their performance in the detection of malignancy, in comparison with p16INK4A and p14ARF, using immunocytochemistry (ICC), immunofluorescence (IF) and Western blot analyses. Most markers were non-specific and could not discriminate HPV infected cancer cell lines from other non HPV malignant. In contrast, nuclear co-expression of p16INK4A and p14ARF was observed only in HPV-transformed cancer cell lines. Notably, in C-33A cervical cancer cells (HPV negative), p14ARF was present in the nucleoli, but p16INK4A was conspicuously absent from the nuclei of these cells. We conclude that both markers; p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer.

Keywords: Cervical cancer cell lines, cervical cancer markers, p14^ARF, p16^INK4A

DOI: 10.3233/CBM-2011-0223

Journal: Cancer Biomarkers, vol. 8, no. 6, pp. 341-350, 2011