Loss of Fhit expression is associated with poorer survival in gastric cancer but is not an independent prognostic marker

Abstract

Several studies have reported conflicting results regarding correlations of the loss of Fhit expression with clinicopathological parameters in gastric cancer. We investigated the immunohistochemical expression of Fhit in 362 cases of sporadic advanced gastric adenocarcinoma. The series included 64 cases with microsatellite instability associated with defective mismatch repair genes. Fhit expression resulted absent in 72% of the tumors analyzed. Absence of Fhit expression was more frequent in cases with diffuse and mixed histotype compared to the intestinal histotype (P=0.009). Absence of Fhit expression also correlated with tumor stage (P<0.001), lymph node involvement (P<0.001), presence of distant metastasis (P=0.033), and increasing histological grade (P=0.005). Retained Fhit expression also correlated with microsatellite instability as 61% of instable tumors had lost Fhit expression compared to 74% of microsatellite stable cancers (P=0.050). While loss of Fhit correlates with poorer survival in univariate analysis, it is not an independent prognostic factor in multivariate analysis and is thus not of clinical utility.

Helicobacter pylori Infection and Family History of Gastric Cancer Decrease Expression of FHIT Tumor Suppressor Gene in Gastric Mucosa of Dyspeptic Patients

“…The genetic contribution to gastric carcinoma is proved in 1–3% of cancer cases representing familial GCs of intestinal, mixed and diffuse subtypes [1]. Early studies carried out on numerous gastric cancer samples revealed the loss of a tumor suppressor fragile histidine triad (FHIT) protein in the majority of cases (more than 70%) and it was more frequent in GC with the diffuse and mixed histotype compared with the intestinal histotype [2,3]. Alterations in the FHIT gene expression have also been found in primary tumors and cancer cells of lung, breast, head and neck, esophagus, colon and rectum, pancreas, kidney, cervix, and hepatocellular carcinoma [4,5].…”

FHIT down-regulation was inversely linked to aggressive behaviors and adverse prognosis of gastric cancer: a meta- and bioinformatics analysis

“…There appeared the comparison between FHIT expression and clinicopathological characteristics of gastric cancer in 19 pieces of paper, including sex, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and Lauren's classification [ 17 – 36 ]. Finally, we discussed the prognostic significance of FHIT expression in 7 articles [ 20 , 25 , 30 – 32 , 36 , 37 ].…”

Fhit down-regulation is an early event in pancreatic carcinogenesis

“…Detection was with streptavidin-biotin complex using the LSAB2 system (DAKO, Carpinteria, CA) with diaminobenzidine as chromogen. Appropriate positive and negative controls were selected from a previous series of gastric samples already characterized for Fhit expression [38] and run concurrently.…”