TP53 gene mutations and protein accumulation in primary vaginal carcinomas

Abstract

Summary Primary carcinomas from 46 patients were screened for TP53 alterations. Immunohistochemistry demonstrated nuclear TPS3 protein accumulation in 22 (48%) cases using the polyclonal CM1 antiserum, whereas 15 (33%) cases showed positive nuclear staining with the mononuclear antibody PAb 1801. Constant denaturant gel electrophoresis (CDGE) was used to screen 27 of the vaginal carcinomas for mutations in the conserved regions of the TP53 gene (exons 5-8 (Lane and Benchimol, 1990). Although the precise mechanism by which the TP53 protein participates in these cellular functions is not fully understood, several biochemical features of TP53 have been elucidated. The TP53 protein is able to regulate transcription directly (Kern et al., 1991;El-Deiry et al., 1992) or by interacting with other transcriptional regulatory factors, such as the TATA-and CAAT-binding proteins (Seto et al., 1992;Agoff et al., 1993). The TP53 protein has also been shown to act as a specific transcription factor controlling the expression of growth arrest genes such as GADD45 (Kastan et al., 1992) and WAF-I (El-Deiry et al., 1993).Mutations in the TP53 gene are the most frequent genetic alteration found in human tumours (Hollstein et al., 1994; Levine et al., 1994

Prognostic Significance of Cell Cycle- and Invasion-Related Molecular Markers and Genomic Instability in Primary Carcinoma of the Vagina

“…However, no significant association between TP53 alteration and survival has so far been observed in PCV. 11,13 In the present study, in agreement with previous reports, we found that most of PCV patients had no overexpression of p53 (81%). However, we noticed that overexpression of p53 was significantly associated with short-term survival.…”

“…11,13,30,37 In the study by Habermann et al, 30 low expression of p53 was detected in 14 of 16 PCV together with high expression of p21 (WAF-1). Skomedal et al 13 investigated 46 PCV and found that 50% had a TP53 gene mutation and/or protein accumulation, with a 70% correlation between mutation and immunohistochemical data.…”

Anal Carcinoma: A Clinical Approach to p53 and RB Gene Proteins

“…In the present study there were no significant correlations between p53 protein accumulation and sex, age, tumour stage at diagnosis, histopathological tumour grading or prognosis. This is in accordance with previous studies that failed to find prognostic significance of p53 in carci nomas of the ovary [ 18], uterine cervix [ 19], vagina [20], colon [21] and head and neck [22], In contrast, other stud ies have demonstrated a relationship between p53 abnor malities and aggressive behaviour of breast [23], uterine [24] and gastric [25] carcinomas. It is uncertain if these differences represent true biological effects of p53 or if they only reflect methodological errors.…”

TP53 protein accumulation and gene mutation in relation to overexpression of MDM2 protein in ovarian borderline tumours and stage I carcinomas

“…Previous studies have revealed varying degrees of discordancy. 31,32 Six cases with eight mutations in the TP53 gene did not show positive immunostaining. Mutations -+ *Four semi-quantitative classes were used to describe the number of immunostained tumour cells: , none; +, less than 5 per cent of the cells; + +, 5-50 per cent of the cells; and + + +, more than 50 per cent of the cells.…”