The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

Abstract

Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent studies have focused on the TP53 tumour suppressor gene, analysing its gene status and protein status. When looking at p53 protein expression, using immunohistochemistry, no correlation to patient outcome has been seen for the whole group of SCCHN. However, a significant association between p53 expression and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning the prognostic significance of mutations in the TP53 gene, results differ. But when restricting analysis to tumours with mutations causing an obvious change in protein, TP53 mutation was found to be a strong and independent variable for prognosticating survival. This review article gives an up-to-date overview of the p53 molecule and evaluates its possible prognostic role in SCCHN. Today it is clear that the p53 pathway is very important in SCCHN biology and potentially in its treatment. The function and importance of a few other cell cycle proteins connected to p53 are also discussed.

p53 Expression Helps Identify High Risk Oral Tongue Premalignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases

“…Studies by Cruz et al (2002) with a follow up of dysplastic lesions for a period of 16 years show that p53 expression pattern could show higher specificity than histopathological assessment of dysplasia (96 % vs. 54 %) and higher positive predictive value (86 % vs. 44 %) for correct prediction of the malignant transformation of the lesions suggesting that clear expression of p53 above the basal cell layer could be an early event in oral carcinogenesis and an indicator of a developing carcinoma, even preceding morphological tissue alterations (Nylander et al, 2000). Conversely, studies also show that patients with negative p53 expression may not have the risk of oral tongue cancer provided they quit the tobacco habit, the known risk promoting factor as confirmed previously (Rich et al, 1999).…”

Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas

“…Structurally, the p63 gene is located on chromosome 3q27-29 4 and encodes three isoforms, p63α, p63β and p63γ, which share a common amino-terminal end but differ at their carboxyl-terminal ends due to alternate mRNA splicings 5 . In addition, the gene for p63 contains a second promoter located upstream of exon 3, which gives rise to three amino-terminal deleted (p63ΔΝ) transcripts.…”

“…This is in contrast to other myoepithelial markers such as calponin and smooth muscle actin, which can show variable myofibroblastic staining. A direct role for p63 in tumorogenesis has not been demonstrated to date, although amplification of the 3q27 region has been seen in a number of tumors, including squamous cell carcinoma 4 . This is suggestive of a putative role as an oncogene rather than as a tumor suppressor gene 6 .…”

Functional analysis of p53 gene and the prognostic impact of dominant‐negative p53 mutation in endometrial cancer

“…MDM2 degrades p53 protein through ubiquitination of the protein, and reduced MDM2 production will lead to an accumulation of p53 protein in the nucleus, which is detected as overexpression by IHC. 8 IHC is a convenient method for the investigation of p53 status. However, it can be affected by many factors, such as antibody used, antigen retrieval technique and subjectivity of criteria for p53 overexpression.…”