Overexpression of chromatin assembly factor‐1 p60, poly(ADP‐ribose) polymerase 1 and nestin predicts metastasizing behaviour of oral cancer

Massimo Mascolo,Stefania Staibano,Gaetano De Rosa,Maria Luisa Vecchione,Gennaro Ilardi,Maria Siano,Maria Fiammetta Romano,Chiara Luise,Simona Romano,Alba Rocco,Angela Celetti,Francesco Merolla

doi:10.1111/j.1365-2559.2012.04313.x

Abstract

AimsThe natural history of oral squamous cell carcinomas (OSCCs) is variable and difficult to predict. This study aimed to assess the value of the expression of poly(ADP-ribose) polymerase 1 (PARP-1), chromatin assembly factor-1 (CAF-1)/p60 and the stem cell markers CD133, CD166, CD44, CD44v6 and nestin as markers of outcome and progression-free survival in OSCC patients.MethodsClinical data were collected from 66 patients (41 male and 25 female, aged 29–92 years) who underwent surgery for OSCC of the tongue, floor, lips, and palate. During follow-up (range: 12–131 months), 14 patients experienced relapse/metastasis and/or death. The study was performed by immunohistochemistry on paraffin-embedded tumour tissues, western blot analysis of tumour protein lysates and human cell lines, and RNA silencing assays. In addition, the human papillomavirus (HPV) status of primary tumours was evaluated by immunohistochemistry and viral subtyping. Univariate and multivariate analyses were performed to determine the correlation between these parameters and the clinical and pathological variables of the study population.Results and conclusionsWe found that a PARP-1high/CAF-1 p60high/nestinhigh phenotype characterized the OSCCs with the worst prognosis (all HPV-negative). This may be of benefit in clinical management, since radio-enhancing anti-PARP-1 and/or anti-CAF-1/p60 agents may allow radioresistance to be bypassed in the nestin-overexpressing, metastasizing OSCC cells.

Highlights

Oral squamous cell carcinoma (OSCC) is the most frequent cancer of the head and neck region
On account of these postulates, we examined the expression of the stem cell-associated antigens CD133, CD166, CD44 with the v6 variant and nestin in a series of primary and metastatic OSCCs.[35]
We focused on the three proteins (CAF-1 ⁄ p60, poly(ADP-ribose) polymerase (PARP)-1, and nestin) that showed the strongest correlation with each other (Table 5) and with tumour biological behaviour

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the most frequent cancer of the head and neck region It represents the fifth most common cancer worldwide, and is the sixth most common cause of cancer-related deaths per year in the USA.[1,2] The major risk factors for this tumour are prolonged exposure to tobacco and alcohol. On the basis of evidence that a distinct cohort of head and neck cancers testing positive for high-risk (HR) human papillomavirus (HPV) DNA shows less aggressive behaviour and better response to therapy, we related our data to the HPV status of primary tumours.[36,37,38,39] As HR HPVs cause strong expression of p16INK4a, a component of the Rb tumour suppressor gene pathway, and immunohistochemistry for p16INK4a is considered to be a reasonable surrogate for detecting transcriptionally active HPV infection, p16INK4a expression was investigated in our cases of OSCC.[40,41,42,43] we explored the existence of any significant association between the several parameters that we analysed and the clinical course of OSCC

Materials and methods patients and tissue samples

G1 5 G2 19 G3

Findings

Discussion