Comparative analysis of p53 gene mutations and protein accumulation in human non‐small‐cell lung cancer

Abstract

A series of 54 resected primary non-small-cell lung carcinomas was analyzed for p53 gene mutations and for p53 protein accumulation and the findings were correlated with clinical parameters. Mutations in exons 5 through 8 of the p53 gene were identified by a denaturing gradient gel electrophoresis (DGGE) assay and cycle sequencing, whereas p53 protein accumulation was detected in paraffin-embedded tissue by immunostaining using 2 different murine monoclonal antibodies (MAbs) (BP53-12 and DO7). A p53 gene mutation and/or p53 protein accumulation was found in 37 of 54 tumors. Mis-sense mutations were closely associated with positive immunostaining, which was intense in 15 out of 17 cases with a mutation. In 10 tumors, obvious p53 accumulation was detected in the absence of mutations in exons 5 through 8. Conversely, only one of 8 p53 non-sense mutations led to detectable p53 accumulation. The most frequent single base changes were G --> T transversions and C --> T transitions. The presence of a p53 alteration was not related to age, tumor size, stage or histology. However, we found a significant inverse correlation between p53 alterations and the presence of a K-ras mutation. This was reflected in the overall postoperative survival data: patients with p53 alterations in their tumors tended to have a better prognosis than those without a p53 alteration; however, this difference was lost when cases with a K-ras mutation were omitted from the analysis.

Regulation of histone modification and chromatin structure by the p53–PADI4 pathway

“…7d). As many of p53 mutations lead to a prolonged half-life of p53 protein, immunohistochemistry of p53 is commonly used to detect p53 mutations in various cancers 24,25 . Interestingly, the positive p53 staining was inversely associated with cit-H4R3 staining (P = 0.0079 by Student's t-test), indicating the regulation of chromatin modification by p53 in human carcinogenesis (Table 1).…”

Multiple molecular marker testing (p53, C-Ki-ras, c-erbB-2) improves estimation of prognosis in potentially curative resected non-small cell lung cancer

“…Mitsudomi and colleagues (1993) also showed a significant negative prognostic impact of p53 mutations (P < 0.01) but subgroup analysis revealed significant prognostic differences for advanced UICC stages IIIA to IV (P < 0.009) and not for early stages I and II (P = 0.28). On the contrary, Top et al (1995) who evaluated 54 patients with resected NSCLC did see a better prognosis in p53 mutationpositive tumours. The lung cancer study group 871 (Carbone et al, 1994) failed to show a prognostic impact in curatively resected NSCLC carrying p53 mutations (P = 0.62) but detected a weak negative survival correlation with positive p53 immunostaining (P < 0.05).…”

Roles of Fhit and p53 in Taiwanese surgically treated non-small-cell lung cancers

“…Alteration of the TP53 gene may be involved in the initiation, development, progression, and invasion of lung cancer (Caamano et al, 1991;Sozzi et al, 1992;Marchetti et al 1993;Fontanini et al, 1994). Even though correlation of p53 protein expression with clinical and biological characteristics of lung cancer has been extensively studied, the results of these studies are quite diverse (Top et al, 1995;Passlick et al, 1995;Dalquen et al, 1996;Lee et al 1999;Garinis et al, 2001;Zienolddiny et al, 2001). The results of this study indicated that p53 expression was closely related to distant metastasis of the overall NSCLCs and the adenocarcinoma subtype; and p53 was especially useful as a prognostic factor in adenocarcinoma.…”