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Allelic loss at FHIT is one of the earliest events in the multistep carcinogenesis of cervical cancers, and recent data has shown that FHIT inactivation in dysplastic epithelium is significantly associated with recurrence of cervical dysplasia. Allelic deletions of FHIT have been detected in a significant proportion of transitional cell carcinomas of the bladder, renal cell carcinomas, and gastrointestinal malignancies (esophagus, gastric and colorectal cancers).
The recent availability of a reliable immunohistochemical assay for FHIT expression has facilitated the assessment of protein expression in routinely fixed archival tissues. Studies comparing FHIT expression with the status of the FHIT gene have shown significant concordance in a variety of malignancies. The FHIT gene, like many other tumor suppressor genes in the human genome, is inactivated by several mechanisms (allelic loss, mutations and promoter methylation); the advantage of an immunohistochemical assay is that it can determine intratumoral FHIT levels irrespective of the mechanism of FHIT gene inactivation. Loss of FHIT expression has been correlated with a variety of clinicopathologic parameters such as disease stage, tumor progression, recurrence and overall survival in lung, breast, bladder and gastrointestinal cancers. These studies have validated the use of the FHIT antibody as a potential biomarker in disease stratification and outcome prediction.
Veripath OncoDiagnostics offers FHIT as part of the standard esophagus, stomach and cervical cancer panels, but it can also be ordered individually. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade for FHIT finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Capuzzi D et al. FHIT expression in gastric adenocarcinoma: correlation with disease stage and survival. Cancer 88:24; 2000
2. Lin WM et al. Allelic loss and microsatellite alterations of chromosome 3p14.2 are more frequent in recurrent cervical dysplasias. Clin Cancer Res 6:1410; 2000
3. Ohta M et al. The FHIT gene spanning the chromosome 3p14.2 fragile site, and renal cell carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell 84:587; 1996
4. Shimada Y et al. Loss of fragile histidine triad gene expression is associated with progression of esophageal squamous cell carcinoma, but not with patient's prognosis and smoking history. Cancer 89:5; 2000
5. Tomizawa Y et al. Clinicopathologic significance of Fhit expression in stage I non-small cell lung carcinoma. Cancer Res 58:5478; 1998
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