Abstract

Objective: The tumor suppressor genes, Fragile Histidine Triad (FHIT) and WW domain-containing oxidoreductase (WWOX) are encoded by fragile loci FRA3B and FRA16D at chromosomes 3p14.2 and 16q23.3. The expression of their protein products has been shown to decrease in several types of cancers. This concordant loss of expression suggests that these common fragile regions of the genome, where certain environmental and/or chemical factors result in damage, have important functions in carcinogenesis. The aim of this study was to determine the prognostic significance of the expression of the FHIT and WWOX genes in laryngeal cancer.

Materials and methods: Sixty-two patients who underwent surgery for laryngeal cancer were investigated for this study. Factors taken into consideration are: age, gender, tumor stage, presence of lymph node metastasis, presence of distance metastasis, location of the tumor, tumor infiltration, length of clinical follow-up, length of remission period, the presence or absence of postoperative supplementary treatment, histopathologic differentiation of the tumor, volume of tumor, cartilage invasion, the presence of perineural invasion, and the condition of surgical resection margins have been detected. The obtained results were compared to the immune histochemistry findings.

Results: Loss of FHIT expression was demonstrated in 39 (62.9%) patients and loss of WWOX expression was demonstrated in 29 (46.8%) patients. There were statistically significant differences between FHIT distributions of the T-stages (p:0.04). FHIT reduction was associated with tumor infiltration (p=0.05). It was also associated with lymph node metastasis (p=0.012). FHIT expression significantly decreased in patients with a history of smoking (p=0.006). There was a statistically significant difference between WWOX expression and the tumor stage (p:0.036), but WWOX expression was not associated with tumor infiltration, lymph node metastasis or smoking history. The other parameters, namely perineural invasion, surgery margins, cartilage involvement, postoperative therapy, disease-free survival, and the tumor’s location did not correlate with WWOX and FHIT expression.

Conclusion: These results showed that the FHIT and WWOX genes may play a role in the prognosis of laryngeal cancer.

Keywords: FHIT, WWOX, Larengeal cancer, Metastas