Expression of biomarkers (p53, transforming growth factor alpha, epidermal growth factor receptor, c-erbB-2/neu and the proliferative cell nuclear antigen) in oropharyngeal squamous cell carcinomas

Abstract

Using immunohistochemistry, expression of p53, transforming growth factor-alpha (TGF-a), epidermal growth factor receptor (EGFR), c-erbB-2/neu and proliferating cell nuclear antigen (PCNA) was examined in 26 fresh frozen tissue specimens of oropharyngeal squamous cell carcinomas (SCCs). p53 gene mutations were examined by polymerase chain reaction (PCR)/DNA sequencing methods in 22 carcinomas. The ®ndings were examined for correlations with patients' clinicopathological parameters. Expressions of p53 and PCNA were also examined in 21 formalin-®xed corresponding tissues. Of the fresh frozen tissue specimens, 77% (20/26) showed expression and 68% (15/22) showed mutations (substitutions) of the p53, with signi®cant clustering of the mutations in exons 5 (8/22; 36%), 7 (4/22; 18%) and 8 (5/22; 23%). No mutations were found in exon 6. There was a discordance between expression of p53 protein and mutations of the gene. Parallel to expression and mutations of the p53 found in most of the specimens, expression of TGF-a, EGFR, c-erbB-2/neu and PCNA was found in 88% (22/25), 92% (23/25), 58% (14/24) and 91% (21/23) of the specimens, respectively. For the formalin-®xed tissue specimens, 62% (13/21) and 90% (19/21) expressed p53 and PCNA, respectively. Examining for correlations with patients' clinicopathological parameters, expression of p53, TGF-a, EGFR and c-erbB-2/neu seemed to negatively correlate with the increase of the tumour grade. The present work suggests that: (1) lack of negative growth regulation due to inactivation of the p53 gene together with activation of other proto-oncogenes are necessary genetic events in the carcinogenesis of oropharyngeal SCCs; (2) in oropharyngeal SCCs, p53 gene mutations were clustered in exons 5 (codons 130±186), 7 (codons 230±248) and 8 (codons 271±282) which perhaps suggests that tobacco carcinogens probably aect the mutational hot spots of the p53 gene at codons 157, 175, 186, 248, 273 and 282; and (3) fresh frozen and formalin-®xed tissue specimens give similar results when an immunohistochemical method is applied. The importance of p53, TGF-a, EGFR, c-erbB-2/ neu and PCNA as biomarkers in oropharyngeal SCCs deserves particular attention because it might oer further understanding of the development of these carcinomas. #

Salivary Her2/neu Levels in Differentiation of Oral Premalignant Disorders and Oral Squamous Cell Carcinomas

“…In fact all the three groups had almost similar levels of serum Her2/neu. The probable reason behind this may be because majority of the OSCC patients were from stage I, which corroborates with previous report suggesting that Her2/neu expression was higher only in late stage or during metastasis (Ibrahim et al, 1999). …”

Coexpression of p53 and Ki 67 and lack of c-erbB2 expression in oral leukoplakias in India

“…17,18 While c-erbB2 membrane expression has been correlated with gene amplification, the significance of cytoplasmic c-erbB2 expression, which was largely observed in our cases, is not exactly known but has been postulated to represent incomplete receptor degradation. 19 In the literature, the results of c-erbB2 immunostaining have been reported to be extremely variable, since both cytoplasmic staining and membranous staining are considered positive. 18 In this study, distinct c-erbB2 membrane staining was not observed in any case.…”

Classical and molecular cytogenetic analysis in head and neck squamous cell carcinomas

“…In addition, several studies have demonstrated increased HER2/ERBB2 oncoprotein levels (Werkmeister et al, 1996;Ibrahim et al, 1999;Xia et al, 1999).…”