Retinoblastoma and p53 protein expression in pre-malignant oral lesions and oral squamous cell carcinoma

Abstract

Abstract. The retinoblastoma (Rb) and p53 genes play a fundamental role in cell cycle mechanisms, and their deregulation is related to many steps of oral cancer carcinogenesis. This study was conducted to evaluate the expression of the p53 and Rb proteins in malignant and pre-malignant oral cavity lesions. This retrospective study was conducted at the Federal University of Bahia, Salvador, Brazil, and the Molecular Biology Laboratory of the Otorhinolaryngology Department at the University of Heidelberg, Heidelberg, Germany. Excisional biopsy samples of oral cavities were collected from patients with suspected oral lesions. The samples were processed by immunohistochemistry to be classified by a semi-quantitative score: samples with a ≤10% positivity were considered to have weak/negative expression (-); those with 11-50% positivity, moderate expression (+); and those with >50% positivity, high expression (++). Seventy-one patients were studied (75% male; median age, 52 years; range, 24-84). Of the samples studied, 59.4% were oral squamous cell carcinoma (OSCC) and 40.6% were pre-neoplastic lesions (leukoplakia and actinic cheilitis). OSCC presented higher expression of Rb protein compared to pre-malignant lesions: 75 vs. 25% (p<0.001). Pre-neoplastic lesions presented higher expression of p53 protein compared to OSCC lesions: 55.2 vs. 44.8% (p= 0.030). Despite the small number of samples, the expression of these cell cycle biomarkers (p53 and Rb protein) in excisional biopsies suggests that molecular lesion assessment can determine pre-malignant lesions, and that its use may improve the clinical and surgical treatment of early lesions. Thus, p53 protein expression may be related to the early steps of carcinogenesis in OSCC. Finally, a higher Rb expression was also observed in malignant lesions.

Predictive Role of p53 Protein as a Single Marker or Associated with ki67 Antigen in Oral Leukoplakia: A Retrospective Longitudinal Study

“…Many studies on oral premalignant and malignant lesions have shown p53 overexpression ranging from 35% to 90% [ 13 , 15 , 27 , 28 ]. Overexpression in OLs was further confirmed in recent studies [ 29 - 33 ]. In particular, De Oliveira et al analyzed p53 protein expression in OSCC and premalignant lesions.…”

“…They found a higher expression of p53 protein in OLs with respect to OSCC lesions (55.2 vs . 44.8%) and emphasized the key role of p53 during early stages of carcinogenesis [ 29 ].…”

The expression of retinoblastoma tumor suppressor protein in oral cancers and precancers: A clinicopathological study

“…The Rb percentage 1-10% showing weak staining for Rb protein was considered as Rb negative and >10% was considered as Rb positive. [ 12 ] As the mean expression of Rb in the various groups of oral lesions was recorded, the Rb positive group was not graded percentage wise.…”

“…Although the alteration in Rb protein expression in tumorigenesis has not been completely elucidated, there is increasing evidence that Rb protein pathway is rendered dysfunctional in oral cancer. [ 12 ] The strong role of pRb in cell cycle regulation prompted us to take up this study, with the aim of assessing the role of Rb protein in the progression of oral cancer, by indicating its expression in the spectrum of lesions ranging from normal to the different histological types of oral cancers. The study also correlates the expression of Rb protein with the clinicopathological parameters including habits like smoking, Paan chewing and alcoholism.…”

Cetuximab Plus Platinum-Based Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Retrospective Study in a Single Comprehensive European Cancer Institution

“…Epidermal growth factor receptor (EGFR) pathways were shown in previous pre-clinical studies to have a major role in SCCHN carcinogenesis by regulating p53 and Rb gene expression. p53 and Rb are regulators of cell cycle control, cell proliferation and apoptosis [14], [15]. More recently, cetuximab, an IgG1 monoclonal antibody against the extracellular portion of the epidermal growth factor receptor (EGFR), was extensively studied in this field [9], [13], [16].…”