Immunohistochemical Detection of p53 Protein in Preneoplastic Lesions and Squamous Cell Carcinoma of the Head and Neck

Abstract

Alterations in the p53 tumor suppressor gene are the most frequent genetic abnormalities in human cancers. The p53 protein is present in normal cells, and is assumed to induce G1 arrest or apoptosis in the presence of DNA lesion. The mutant protein lacks this property. Squamous cell carcinomas of the head and neck (SCCHN) are related to carcinogens in tobacco and alcohol, and provide a good model of multiple-step carcinogenesis in association with DNA damage and p53-related tumorigenesis. Stabilization of the mutant p53 protein allows immunohistochemical analyses (IHC) to be routinely used to demonstrate the mutant p53 protein in tissue samples, whereas normal p53 protein is undetectable. Ninety-nine squamous cell carcinomas, 8 in situ carcinomas, 31 preneoplastic lesions and 79 normal carcinogen-exposed mucosas of the head and neck from a total of 107 patients were examined for the expression of p53 tumor suppressor gene protein. Samples were collected before treatment, and stained with p53 specific mono- and polyclonal antibodies (DO-7, Pab 1801 and 240, CM1) using an indirect immunoperoxidase technique. Proliferating cell nuclear antigen (PCNA) provided semiquantitative estimates of proliferation. The main localizations were the pharynx (64/107) and the larynx (21/107). Positive IHC detection of p53 was observed in 9% of normal-appearing carcinogen-exposed mucosas, 37% of hyperplasias, 68% of dysplasias, 75% of in situ carcinomas, and 56/99 (56.5%) of primary tumor samples. Mucosas from 15 control patients under 10 years of age were negative. There was no correlation between p53 IHC and localization, differentiation or TNM staging.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of human papillomavirus on cell cycle-related proteins p16INK4A, p21waf1/cip1, p53 and cyclin D1 in sinonasal inverted papilloma and laryngeal carcinoma. An <i>in situ</i> hybridization study

“…Our results support the idea of neutralization of the p53 gene suppressor pathways by HPV proteins. In contrast to our results, p53 protein overexpression has been demonstrated in many preneoplastic and neoplastic lesions of the larynx [28][29][30][31][32][33][34][35].…”

“…The wide spectrum probe targets the genomic DNA of HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51 and 52. Further subtyping was carried out in the same way, using specific probes for HPV low risk -LR-HPV (HPV 6 and 11) and HPV high risk -HR-HPV (HPV 16,18,31,33,35,39,45, 51, 52, 56, 58, 59, 68). Afterwards, a catalyzed signal amplification system (prepared according to the instructions of the manufacturer) was used (GenPoint, CSA System for in situ hybridization; Dako).…”

Antigen Retrieval Immunohistochemistry: Past, Present, and Future

“…This is a critical issue in interpreting the results of AR-IHC. Thus far, most studies have reported satisfactory results, without false positivity, for a variety of antibodies tested (Brown and Chirala 1995;Lavieille et al 1995;Cuevas et al 1994;Igarashi et al 1994;Taylor et al 1994a;Tenaud et al 1994;von Wasielewski et al 1994;Cattoretti et al 1993;Dookhan et al 1993;Gown et al 1993a;Leong and Milios 1993;Shi et al 1991). Most recently, Baas et al (1996) questioned whether a potential false-positive result of AR-IHC using the MAb DO7 might be obtained after extreme AR treatment.…”

The Calcium-binding Protein S100A2 Interacts with p53 and Modulates Its Transcriptional Activity

“…The transcription factor p53 is overexpressed in HNSCC (25,26), and its subcellular localization correlates with tumor stage (27) and tumor progression (28). Induction of p53 transactivation activity by DNA damage results in increased S100A2 transcription (29).…”