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. 2012 Dec;61(6):1089-105.
doi: 10.1111/j.1365-2559.2012.04313.x. Epub 2012 Aug 8.

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

Massimo Mascolo  1 , Gennaro Ilardi, Maria Fiammetta Romano, Angela Celetti, Maria Siano, Simona Romano, Chiara Luise, Francesco Merolla, Alba Rocco, Maria Luisa Vecchione, Gaetano De Rosa, Stefania Staibano
Affiliations

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

Massimo Mascolo et al. Histopathology. 2012 Dec.

Abstract

Aims: The 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.

Methods: Clinical 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 conclusions: We found that a PARP-1(high) /CAF-1 p60(high) /nestin(high) 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.

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Figures

Figure 1
Figure 1
A case of metastasizing oral squamous cell carcinoma. A,B, Strong immunostaining for PARP-1 (nuclear) and CD166 (cytoplasmic and cell membrane). C,D, Diffuse immunostaining for CAF-1/p60 (nuclear) and CD44 (cytoplasmic and cell membrane). E,F, Extensive, strong positivity for nestin (cytoplasmic and cell membrane).
Figure 2
Figure 2
A case of oral squamous cell carcinoma, N0 M0, at the end of follow-up. A,B, Low to moderate immunohistochemical expression of nestin and CAF-1 p60. C,D, Weak immunopositivity for CD44 and CAF-1/p60. E,F, Weak staining for CD166 and PARP-1.
Figure 3
Figure 3
Expression of stem cell markers, PARP-1 and CAF-1/p60 in oral squamous cell carcinoma (OSCC) and cell lines. A, Snap-frozen OSCC, protein lysates: high expression level of uncleaved p111 PARP-1 and CAF-1/p60 in primary OSCC (T) and corresponding metastases (N1, N2). All of the evaluated stem cell markers were found to be expressed in OSCC. However, the highest levels were registered for nestin, particularly in metastases. Tubulin detection was used to confirm equal gel loading. B, Cultured human OSCC lines: OSCC cell lines overexpressed CAF-1/p60 and PARP-1. Among stem cell markers, nestin, CD44, CD44v6 and CD166 showed the highest expression levels. A primary culture of HNEK cells was used as control.
Figure 4
Figure 4
CAF-1 p60 silencing activates keratinocyte cell death: flow cytometric histograms of propidium iodide incorporation of HaCat and CAL33 cells, transfected with non-silencing (NS) RNA or CAF-1 p60 small interfering RNA. Twenty-four hours after transfection, cells were treated with the PARP-1 inhibitor PJ34, and were harvested after a further 24 h. Bars indicate hypodiploid cell percentages (B). Graphic representations are given of the mean values and standard deviations of cell death values (n = 6) for HaCat and CAL33 cells (C). The CAF-1/p60 siRNA efficiency was assessed by measuring the levels of CAF-1/p60 mRNA, by Real time PCR (A).
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References

    1. Deshpande AM, Wong DT. Molecular mechanisms of head and neck cancer. Expert Rev. Anticancer Ther. 2008;8:799–809. - PMC - PubMed
    1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J. Clin. 2010;60:277–300. - PubMed
    1. Mydlarz WK, Hennessey PT, Califano JA. Advances and perspectives in the molecular diagnosis of head and neck cancer. Expert Opin. Med. Diagn. 2010;4:53–65. - PMC - PubMed
    1. Schuller DE, Wilson HE, Smith RE, Batley F, James AD. Preoperative reductive chemotherapy for locally advanced carcinoma of the oral cavity, oropharynx, and hypopharynx. Cancer. 1983;51:15–19. - PubMed
    1. Al-Sarraf M. Chemotherapy strategies in squamous cell carcinoma of the head and neck. Crit. Rev. Oncol. Hematol. 1983;1:323–355. - PubMed

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