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Fhit expression is absent or reduced in a subset of primary head and neck cancer
1Department of Otolaryngology, Head and Neck Surgery, University Hospital, Mannheim, Germany. karl.goette@hno.ma.uni-heidelberg.de
Background:
The inactivation of the FHIT gene at 3p14.2 by various mechanisms might be of importance in head and neck squamous cell carcinoma (HNSCC). Most reports are based on DNA and RNA findings of intragenic deletions and abnormal transcripts.
Material And Methods:
To study the protein expression of this putative tumour suppressor gene, we analysed 48 HNSCCs by immunohistochemistry using a polyclonal antibody (ZR44). The results were compared with mutation analysis, clinical data and loss of heterozygosity (LOH) data at 3p14.2.
Results:
Complete absence of Fhit expression was detected in 8 out of 48 of tumours (17%) and 3 tumours (6%) showed heterogenous staining. The overall frequency of LOH for microsatellite D3S1234 was 64% and 5/7 of Fhit negative tumours exhibited LOH.
Conclusion:
Our findings provide further evidence that FHIT is inactivated in a subtype of HNSCC; however, the incidence of lack of Fhit expression compared to the high frequency of LOH on chromosome 3p supports the notion of additional tumour suppressor genes at 3p14.
Insights
The FHIT gene is inactivated in a subset of head and neck squamous cell carcinoma (HNSCC). Protein expression loss was observed in 17% of tumors, suggesting other tumor suppressor genes on chromosome 3p may also be involved.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The FHIT gene, located at 3p14.2, is implicated in head and neck squamous cell carcinoma (HNSCC).
- Previous research focused on DNA and RNA alterations, including intragenic deletions and abnormal transcripts.
Purpose of the Study:
- To investigate the protein expression of the FHIT gene in HNSCC.
- To correlate FHIT protein levels with mutation status, clinical data, and loss of heterozygosity (LOH) at 3p14.2.
Main Methods:
- Immunohistochemistry was used to analyze FHIT protein expression in 48 HNSCC samples using the ZR44 antibody.
- Analysis included comparison with mutation data, clinical information, and LOH data for microsatellite D3S1234 at 3p14.2.
Main Results:
- Complete absence of FHIT protein expression was found in 17% (8/48) of HNSCC tumors.
- Heterogeneous FHIT staining was observed in 6% (3/48) of tumors.
- A high frequency of LOH at 3p14.2 (64%) was detected, with 5 out of 7 FHIT-negative tumors exhibiting LOH.
Conclusions:
- FHIT gene inactivation occurs in a specific subtype of HNSCC.
- The lower incidence of FHIT expression loss compared to LOH suggests the presence of additional tumor suppressor genes at the 3p14.2 locus.