Correlation of p53 protein expression with gene mutation in gall‐bladder carcinomas

Abstract

The correlation of p53 protein expression and p53 mutation of 33 gall-bladder carcinomas was studied according to the depth of invasion and grade of cytological atypia. Overexpression of p53 protein was detected by immunostaining in seven (70.0%) of 10 intramucosal and in 16 (69.6%) of 23 invasive carcinomas. p53 mutation was detected in five (71.4%) of the seven intramucosal carcinomas with overexpression and in eight (50.0%) of the 16 invasive cancers with overexpression and in one (10%) of the 10 non-overexpressing carcinomas at exons 5-8 by nested polymerase chain reaction-single-strand conformation polymorphism. The overexpression of p53 protein was present in nine (56.3%) of 16 low-grade carcinomas and in 14 (82.3%) of 17 high-grade carcinomas. In cases of overexpression, p53 mutation was detectable in four (44.4%) of nine low-grade and in nine (64.3%) of 14 high-grade carcinomas. In total, p53 mutation was verified in 56.5% (13/23) of cases involving protein overexpression and in 10% (1/10) of cases of non-overexpression. The sensitivity of p53 mutation was 56.5% (13/23), the specificity was 90.0% (9/10) and the validity was 1.47. In conclusion, our study indicates that p53 protein overexpression correlates well with gene mutation and that p53 alteration may be related to increasing grade of cytologic atypia of carcinomas.

Expressão imuno-histoquímica e valor prognóstico da proteína p53 no carcinoma de vesícula biliar: estudo de 60 casos

“…Vários estudos (1,8,9,13,16,18,20,25,28,29,36,39,40,42) foram realizados para avaliar a presença de expressão da proteína p53 no CaVB, apresentando resultados conflitantes tanto em relação à sua positividade quanto à significância da imunorreatividade no prognóstico dessa neoplasia. Esse fato pode ser atribuído, em parte, a pequenas amostras estudadas.…”

“…Essa mutação parece desempenhar um importante papel na patogênese de muitas neoplasias malignas, como câncer gástrico (9) , de cólon (43) , mama (38) , pulmão (12) e esôfago (30) , sendo incomum em tumores benignos (12) . A correlação da expressão da proteína p53 com a mutação gênica no CaVB foi avaliada em estudo recente realizado por Itoi et al (13) , que demonstraram uma sensibilidade de 56,5% da mutação p53, especificidade de 90% e validade de 1,47.…”

“…Desde a primeira publicação realizada por Kamel et al (16) em 1993 para avaliar imuno-histoquimicamente a presença de expressão da proteína p53 no CaVB, poucas publicações (1,8,9,13,16,18,20,25,28,29,36,39,40,42) têm sido feitas, com achados bastante variáveis de positividade (entre 36,9% e 95%) e conflitantes em relação à associação dessa mutação com o prognóstico dos portadores dessa neoplasia.…”

K‐ras, p53 mutations, and microsatellite instability (MSI) in gallbladder cancer

“…p53 accumulation was observed in 27-70% of gallbladder carcinomas in various studies [14,[32][33][34][35][36]. Additionally, a gradual increase of p53 protein expression from precancerous lesions to invasive carcinoma has been reported [37].…”

“…Additionally, a gradual increase of p53 protein expression from precancerous lesions to invasive carcinoma has been reported [37]. Notably, indications exist for the correlation of p53 alterations to an increasing rate of cytologic atypia in gallbladder carcinomas [32].…”