p16 Alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract

Abstract

The progression potential of preinvasive epithelial lesions is usually evaluated by assessing the degree of histologic dysplasia. We examined p16, retinoblastoma protein (pRb), and proliferating cell nuclear antigen (PCNA) immunophenotypes in 57 cases of previously untreated squamous cell carcinoma (SCC) of the upper digestive tract and in the neighboring normal and dysplastic epithelia. Tissue samples were examined for homozygous deletion of exon 2 of the p16 gene using polymerase chain reaction (PCR) analysis. The PCNA index increased with increasing grade of dysplasia. The pRb protein was expressed in 89% of the samples of SCCs and in the neighboring dysplasias and carcinoma in situ (CIS). In cases with a lack of pRb expression, corresponding preinvasive lesions were also negative. Lack of p16 expression was found in 82% of SCCs. The prevalence of p16 expression decreased with increasing grade of dysplasia. Molecular analysis of the p16 gene showed homozygous deletion in 37% of SCCs, 33% of CIS, and 15% of the samples of normal epithelia. Our data indicate that inactivation of p16 may play an important role in early head and neck carcinogenesis, whereas the mutation of Rb may be an infrequent event. The p16 immunophenotype might be a biomarker for an increased risk of progression in squamous dysplasia.

Molecular determinants of Akt-induced keratinocyte transformation

“…In addition, mdm2 protein is expressed in HNSCC mostly at advanced stages (Ambrosch and Ruschenburg, 2000). Therefore, it is conceivable that these are not relevant targets in HNSCC.…”

Oral Cavity and Esophageal Carcinogenesis Modeled in Carcinogen-Treated Mice

“…Previous studies reported p16 protein inactivation, resulting from either gene deletion or promoter methylation, in oral cancers (79), esophageal squamous carcinomas (51), upper aerodigestive tract (59), and head and neck squamous carcinomas (80). In control mice, most p16-stained cells were in the basal layer of the tongue epithelium, whereas in invasive carcinomas of the tongue, only a few cells showed p16 staining (Fig.…”

“…p16 is a target commonly involved in esophageal carcinogenesis (51), and the abrogation of p16 occurs frequently in human oral cancers (52). The loss of expression of p16 has been observed in oral premalignant lesions (53,54), primary tumors of the oral cavity (55)(56)(57)(58), and squamous carcinomas of the upper aerodigestive tract (59).…”

p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma

“…Gonzales et al [29] also found association between p16 expression and inflammatory cells. The loss of function of pRB due to mutations or chromosomal deletions may also result in high expression of p16; however, loss of pRB function in the head and neck occurs in a small number of tumors [42].…”