Clinicopathological significance of FHIT protein expression in gastric adenocarcinoma patients

Abstract

Aim: To investigate the expression of fragile histidine triad (FHIT) protein, and the possible relationship between FHIT expression and clinicopathological indices in gastric carcinoma.

Methods: FHIT protein expression was examined in 76 cases of gastric carcinoma, 58 cases of intraepithelial neoplasia, and 76 cases of corresponding normal mucosae by immunohistochemical method to analyze its relationship to histological grade, clinical stage, metastatic status and prognosis.

Results: The FHIT protein expression was positive in 28/76 (36.8%) cases of adenocarcinoma tissue, 22/58 (37.9%) cases of adjacent dysplastic tissue and 76/76 (100%) cases of distal normal gastric mucosa. There was a significant difference in the expression of FHIT protein between cancer or adjacent intraepithelial neoplasia and normal gastric mucosa (P = 0.000). FHIT protein expression was found in 64.3% (18/28) of grades I and II cancers, and 20.8% (10/48) of grade III cancers (P = 0.000), in 56.3% (18/32) of stages I and II cancers and 22.7% (10/44) of stages III and IV cancers (P = 0.004), and in 63.6% (14/22) of cancers without metastasis but only 25.9% (14/54) of those with metastasis (P = 0.003). The significant difference in the expression of FHIT was found between histological grade, clinical stage and metastatic status of cancer. Follow-up data showed that there was a significant difference in median survival time between cancer patients with expression of FHIT (71 mo) and those without (33 mo, log rank = 20.78, P = 0.000).

Conclusion: FHIT protein is an important tumor suppressor protein. Loss of FHIT protein expression may be associated with carcinogenesis, invasion, metastasis and prognosis of gastric adenocarcinoma.

Figure 1

Positive FHIT expression in the normal gastric mucosa (A) and negative FHIT expression in cancer cells (B). (SP ×200).

Figure 2

Difference in median survival time between carcinoma patients with and without FHIT expression ( n = 76). The y-axis represents the percentage of patients, the x-axis represents their survival time. The red line represents FHIT-positive patients with a better survival, the green line represents FHIT-negative gastric carcinoma patients (log rank = 20.78; P = 0.000).