Expression And Clinical Significance Of Tumor Suppressor Gene RASSF1A In The Malignant Progression Of Laryngeal Mucosa

Objective To study the expression of tumor suppressor gene RASSF1A in laryngeal squamous cell carcinogenesis, which induces the epigenetic inactivation of tumor suppressor gene RASSF1A, and analyzing the correlation between transcriptional and protein expression of tumor suppressor gene RASSF1A in the Malignant Progression of faryngeal Mucosa and clinical pathological factors.Methods We used 9 Inflammatory polyps and 50 laryngeal premalignant lesions and laryngeal squamous cell carcinogenesis fresh tissue samples. Inflammatory polyps were used as a source of control. Lesions were classified as:(a) Inflammatory polyps (n=9); (b) keratosis (n=10); (c) papilloma (n=10); (d) high grade dysplasia or carcinoma in situ(HGD) (n=15); and (e) laryngeal squamous cell carcinoma(LSCC) (n=15). In the present study, we used Quantitative RT-polymerase chain reaction (RT-PCR)、 Western-blot and immunohistochemistry analysis to evaluate the transcriptional and protein expression of RASSF1A in the same specients from laryngeal premalignant lesions and SCC to clarify the possible role of RASSF1A in laryngeal squamous epithelial tumors. Expression inactivation of tumor suppressor gene RASSF1A, Statistical incidence of expression inactivation of RASSF 1A and its correlation with clinical pathological factorsResults In this study, firstly we used RT-PCR to evaluate the transcriptional expression of RASSFIA. The results showed that RASSF 1A transcripts were expressed in all inflammatory polyps tissues. The loss transcriptional expression of RASSFIA was up-regulated in LSCC comparing with the inflammatory polyps and premaligant lesions. Significant differences were found between HGD and inflammatory polyps, keratosis, papilloma grades (p<0.05). Significant differences was found between LSCC and inflammatory polyps, keratosis, papilloma grades (p<0.01). But no statistically difference was shown in the inflammatory polyps, keratosis, papilloma grades (p> 0.05). We investigated the protein expression frequency of RASSFIA and clinical relationship with Western-blot and immunohistochemistry analysis. The results similar with transcriptional expression of RASSFIA. Significant differences were found between loss of protein expression and clinical pathological.Conclusions Loss of RASSF 1A mRNA expression occurs increasingly commonly during the genesis and development of LSCC. The incidence of negative protein expression of RASSFIA is higher in the Malignant Progression of laryngeal Mucosa.It was shown that a specific pattern of Epigenetic inactivation of tumor suppressor gene RASSFIA is important marker to predict progression. Therefore, the presently used Real-Time RT-PCR and Western-blot analysis may be sensitive enough to provides strong evidence supporting the role of RASSF1A genetic tests in augmenting histopathological evaluation of laryngeal premalignancies. RASSFIA could be a new useful molecular marker of LSCC gene diagnosis and gene therapy of laryngeal carcinoma. FASSF1A may play an important role in gene diagnosis and gene therapy of laryngeal carcinoma.