Expression And Significance Of Autophagy Factors Beclin1 And MAP1LC3 In Laryngeal Squamous Cell Carcinoma

Objective: Larynx is the foundation of anthropo-pronouning and the portal of the air tube. But with the development of social economy and environment, the disease incidence of laryngeal carcinoma advanced clearly. According to the epidemiology of Northern America and Europe, among one hundred thousand persons, there were 7.0-16.2 persons fell in this disease; in some cities of our country, per one hundred thousand persons, there were 1.5-3.4 persons fell in it. In some hospitals of 13 cities of our country, among the patients with malignant tumors in 1983 to 1992, laryngeal carcinoma accounted to 13.9% in head and neck tumors, accounted to 2.1% in malignant tumors all over the body. The morbidity of laryngeal carcinoma has racial and regional disparity. At the intermediate stage of 1980s,by the census to 160 districts, we knew that the maximal disease incidence of laryngeal carcinoma in the world happened in Spain, France, Italy and Poland. In our country, the disease incidence of northern china and northeast outclass every province in south of the River. Male are more than female (8:1), aged from 40 to 60 are more. In the malignant tumors of larynx, 96%-98% are squamous cell carcinoma (SCC). Like any other malignant tumor, the treatment strategies for laryngeal carcinoma include surgery, radiotherapy, chemotherapy and immunotherapy, but with the development of science, gene therapy has become a new treatment strategy. In the past few years, recepted by majority scholars was that dividing programmed cell death (PCD) to apoptosis programmed cell death and autophagy programmed cell death. Besides the role of cell death, autophagy cannot be neglected in the role of retaining cell life. Ashford and Porten observed the phenomenon of autophagy in the hominal hepatic cells using the electron microscope in 1962.It was believed as one kind of cell reaction, which was used to gain nutrient substance and digest organelles. With the establishment of yeast model and the development of gene technology, it was not until recent 10 years that the comprehension to the molecule mechanism and appearance feature of autophagy has gradually gone deeply. Autophagy is the instrument that can lead to cell survival and death directly. The defection of autophagy will lead to the occurrence of tumors. Mammalian autophagy related genes have been named Atg uniformly from original Atg/Apg/Aut/Cut.Beclin1, originally identified as a novel Bcl-2- interacting protein, whose molecular mass is 60KDa and it is homologues gene of autophagy related gene—Atg6 of mammalian. It is identified as the first functional mammalian autophagy gene and resides at human tumor susceptibility locus - chromosome 17, on which there are monoallelic deletion in large numbers of breast, prostate and ovarian cancers. Because it can induce to autophagy cell death, so it has become a new method to cure tumors. But in cells, our cognition is very spare to the molecular mechanisms mediated by Beclin1.MAP1LC3 is the congener of yeast Atg8, which was the first autophagosome membrane protein observed in advanced eukaryotic cells and identified as the basical components of autophagy lysosome. MAP1LC3 has two forms, their molecular mass are 18KDa and 16KDa respectively,which caused by modification after translation. It locates in pre- autophagic vacuole, autophagic vacuole membrane and autophagosome. Recently, three human subtypes of MAP1LC3 have been cloned (MAP1LC3A, -B, and -C). It is a novel marker of autophagosome. This experiment studies the expression of autophagy related genes Beclin1 and MAP1LC3 in laryngeal squamous cell carcinoma (LSCC) tissues and normal tissues adjacent to cancer. Studying the expression of the two factors in different pathological grade, clinical stage, tumor sit and lymph node metastasis of LSCC and the correlation of the two factors. Offering the theoretical basement for the purpose of applying the knowledge of autophagy to diagnosis and treatment of laryngeal carcinoma.Method: Choosing forty-nine LSCC tissues and thirty normal tissues adjacent to cancer. First, defining LSCC tissues and normal tissues adjacent to cancer by HE dyg. Then observing the expression of Beclin1 and MAP1LC3 in forty-nine human LSCC tissues and thirty normal tissues adjacent to cancer by immunohistochemistry (IHC) method and studying the expression of the two factors in different pathological grade, clinical stage, tumor sit and lymph node metastasis of LSCC and the correlation of the two factors. Statistical dates were analyzed by SPSS16.0- statistical software. X 2 test was used to detect the expression of Beclin1 and MAP1LC3 in LSCC tissues and normal tissues adjacent to cancer and the expression of the two factors in different pathological grade, clinical stage, tumor sit and lymph node metastasis of LSCC. Spearman rank correlation test was used to detect the correlation of the two factors.Results:1 The positive rate of Beclin1 in LSCC and normal tissues adjacent to cancer was 24.49% and 100% respectively. The positive rate of MAP1LC in the two tissues was 18.37% and 90% respectively. The positive rate of the two factors in LSCC was both obviously lower than in normal tissues adjacent to cancer (P<0.05).2 The positive rate of Beclin1 in well-differentiated LSCC was 28.57%, 14.29% in poorly-differentiated. There was no statistical significance (P>0.05). The positive rate of MAP1LC3 in well differentiated and poorly differentiated was 22.86% and 7.14% respectively. There was no statistical significance (P>0.05).3 The expression rate of Beclin1 in LSCC with lymph node metastasis and without was 4.34% and 42.31% respectively, there was statistical significance (P<0.05). The expression rate of MAP1LC3 was 0% and 34.62% respectively, there was statistical significance (P<0.05). 4 The positive rate of Beclin1 inⅠ-Ⅱstages andⅢ-Ⅳstages was 31.03% and 15% respectively, there was no statistical significance (P>0.05). The positive rate of MAP1LC3 in the two stages was 20.69% and 15% respectively, there was no statistical significance (P>0.05).5 The positive rate of Beclin1 in supra-glottic and glottic laryngeal carcinoma was 26.92% and 21.74% respectively, there was no statistical significance (P>0.05). The positive rate of MAP1LC3 in the two types was15.38% and 21.74% respectively, there was no statistical significance (P>0.05).6.There were no correlation between Beclin1 and MAP1LC3 expression in LSCC (P>0.05).Conclusion: The expression of Beclin1 and MAP1LC3 in LSCC were both obviously lower than normal tissues adjacent to cancer. Both the expression of Beclin1 and MAP1LC3 in LSCC with lymph node metastasis were obviously lower than that without. The expression of Beclin1 and MAP1LC3 were related to laryngeal carcinogensis and metastasis. There were no correlation between MAP1LC3 and Beclin1 expression in LSCC.