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Published on: January 22, 2018
Fhit expression in gastric adenocarcinoma: correlation with disease stage and survival
D Capuzzi1, E Santoro, W W Hauck
1Department of Pathology, Anatomy, and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Background:
The FHIT gene is inactivated by deletion in a large fraction of human tumors, including gastric carcinomas, and the Fhit protein has been proposed to act as a tumor suppressor in multiple tumor types. A large fraction of gastric adenocarcinomas have lost expression of the candidate tumor suppressor protein, Fhit, whereas normal gastric epithelial cells are strongly positive and Fhit loss has been found to correlate with alterations of the FHIT locus. Because the majority of gastric tumors in the current study were found to be entirely negative for Fhit protein, it is possible that alteration of the carcinogen-susceptible fragile region within the FHIT gene is an early event in gastric carcinoma, as it is in lung carcinoma.
Methods:
To determine whether the absence of Fhit protein correlates with expression of tumor markers or with clinical parameters, such as grade, stage, and survival time, the authors assessed Fhit expression using immunohistochemistry in a well characterized set of 55 gastric adenocarcinomas resected over several years, with longitudinal follow-up of patients for outcome.
Results:
In this set of 55 gastric cancers, the absence of Fhit protein correlated with higher tumor stage (P = 0.003) and higher histologic grade (P = 0.007). In addition, patients whose tumors had lost expression of Fhit died of disease significantly earlier than those with Fhit positive tumors (P = 0.017). The absence of Fhit expression did not correlate with the expression of any tumor markers.
Conclusions:
Larger studies will be required to elucidate further the relation between tumor stage, grade, and Fhit loss and to determine whether inclusion of Fhit antiserum in immunophenotyping of gastric adenocarcinomas will be a useful indicator of post-diagnosis prognosis.
Insights
Loss of Fhit protein in gastric cancer correlates with advanced stage and poor survival. Further studies are needed to confirm Fhit as a prognostic marker in gastric adenocarcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- The FHIT gene, a candidate tumor suppressor, is frequently inactivated in human cancers, including gastric carcinomas.
- Loss of Fhit protein expression is observed in a significant proportion of gastric adenocarcinomas, contrasting with normal gastric cells.
- FHIT gene alterations may represent an early event in gastric carcinoma development.
Purpose of the Study:
- To investigate the correlation between Fhit protein absence and tumor markers or clinical parameters in gastric adenocarcinomas.
- To assess the relationship between Fhit expression and patient survival outcomes.
Main Methods:
- Immunohistochemistry was used to evaluate Fhit protein expression in 55 gastric adenocarcinomas.
- Patient data, including tumor stage, grade, and survival time, were analyzed in conjunction with Fhit expression levels.
Main Results:
- Absence of Fhit protein significantly correlated with higher tumor stage (P = 0.003) and histologic grade (P = 0.007).
- Patients with Fhit-negative tumors exhibited significantly shorter survival times compared to those with Fhit-positive tumors (P = 0.017).
- No correlation was found between Fhit expression and the expression of other tumor markers.
Conclusions:
- Fhit loss in gastric adenocarcinomas is associated with adverse clinicopathologic features and poorer prognosis.
- Further research with larger cohorts is necessary to validate Fhit as a prognostic indicator in gastric cancer.
- The utility of Fhit antiserum in immunophenotyping for predicting patient prognosis warrants further investigation.
