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Published on: June 14, 2019
Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication
Shyh-Kuan Tai1, Janet I Lee, K Kian Ang
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Purpose:
Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT.
Experimental Design:
Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years.
Results:
Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%).
Conclusions:
Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control.
Insights
Loss of Fhit protein expression in head and neck squamous cell carcinoma (HNSCC) indicates a poorer prognosis. However, Fhit-negative tumors may respond better to postoperative radiotherapy, potentially improving locoregional control.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- FHIT (Fragile Histidine Triad) is a candidate tumor suppressor gene implicated in various cancers.
- Abnormalities in FHIT are frequently observed in head and neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To investigate the role of Fhit protein expression in HNSCC patients undergoing surgery and postoperative radiotherapy (PORT).
- To correlate Fhit expression status with clinicopathological characteristics and clinical outcomes in HNSCC.
Main Methods:
- Immunohistochemical staining was used to assess Fhit protein expression in 80 HNSCC tissue samples.
- Clinicopathological data and clinical course were analyzed, with a median follow-up of 4.9 years.
Main Results:
- Fhit expression was lost in 65% of HNSCC patients.
- Loss of Fhit expression was associated with significantly worse 5-year overall survival.
- Fhit-negative tumors showed a higher rate of distant metastasis but paradoxically lower locoregional recurrence in high-risk patients.
Conclusions:
- Loss of Fhit expression serves as a poor prognostic indicator for HNSCC patients.
- Fhit-negative HNSCC tumors might exhibit increased sensitivity to PORT, potentially enhancing locoregional control.
