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

Abstract

Abnormalities of fragile histidine triad (FHIT) and TP53 have been found frequently in nonsmall cell lung cancers. In the current study, 263 primary nonsmall cell lung cancers were investigated for the expressions of Fhit and p53 by immunohistochemistry. Marked reduction of Fhit immunoreactivity (o10% positivity) in 156 (59%) tumours and overexpression of p53 protein (410% positivity) in 89 (34%) tumours were found. Reduced Fhit expression was also noted in most squamous cell carcinomas (80 out of 99, 81%), and in a smaller fraction of adenocarcinomas (76 out of 164, 46%; Po0.001). p53 nuclear staining was demonstrated in 54 out of 99 (55%) squamous cell carcinomas and in 35 out of 164 (21%) adenocarcinomas (Po0.001). The loss of Fhit expression and p53 overexpression was significantly more common in tumours occurring in smokers (93 out of 113, 82% and 56 out of 113, 50%) than in those of nonsmokers (63 out of 150, 42%; Po0.001 and 33 out of 150, 22%; Po0.001). Notably, p53 overexpression was associated with distant metastasis of patients in the whole series (P ¼ 0.027) and in adenocarcinoma (P ¼ 0.001). It was also associated with a poorer survival of patients with adenocarcinoma (P ¼ 0.032).

Frequent allelic deletion at the FHIT locus associated with p53 overexpression in squamous cell carcinoma subtype of Taiwanese non-small-cell lung cancers

“…Abnormalities of p53 expression by immunostaining were frequently found in lung cancer including 40 -70% of SCLCs and 40 -60% of NSCLCs. Previous reports, in our study of Taiwanese NSCLCs, have also indicated that p53 nuclear expression by immunostaining analysis detected more frequent stainable expression in squamous cell carcinoma than that in adenocarcinoma (Chang et al, 2003) In addition, p53 overexpression and the loss of Fhit expression has been significantly more common in tumours from smokers than those of nonsmokers (Chang et al, 2003).…”

“…It was previously indicated that the genetic changes at the FHIT locus may be correlated with p53 mutations (Burke et al, 1998;Marchetti et al, 1998;Chang et al, 2003), while other investigators found no statistically significant correlation between FHIT and p53 abnormalities in NSCLCs (Nelson et al, 1998;Geradts et al, 2000). By examining the FHIT/ p53 profiles, we noticed that the nine cases with synergistic effect of LOH at FHIT locus and p53 overexpression included six squamous cell carcinomas and three adenocarcinomas.…”

Clinicopathologic characteristics and prognostic significance of EGFR and p53 mutations in surgically resected lung adenocarcinomas ≤2 cm in maximal dimension

“…Some studies have shown that p53 mutation or overexpression is an indicator of poor prognosis, especially in patients with lung adenocarcinoma [12]. Our previous studies revealed that p53 expression was an independent prognostic factor in stage I NSCLC [18] and was associated with distant metastasis in NSCLC patients and poorer survival in adenocarcinoma patients [23]. The present study showed that p53 mutation was associated with tumor relapse in stage I, but not stage IA, patients with surgically resected small adenocarcinomas, which suggested that p53 mutation was a risk factor…”

Early Loss of Fhit in the Respiratory Tract of Rodents Exposed to Environmental Cigarette Smoke

“…Several studies, using either immunohistochemical or molecular methods, showed a significant loss of Fhit in lung cancers from smokers compared with lung cancers from nonsmokers (3)(4)(5)(6)(7)(8)(9). Interestingly, a dose-dependent decrease of Fhit methylation was observed in bronchoalveolar lavage cells from cancer-free patients undergoing fiber optic bronchoscopy, as related to the number of cigarettes smoked in a lifetime (10).…”