ABSTRACT
Background and study aim: Laryngeal squamous cell carcinoma [SCC] is the most frequent tumor of the head and neck region. Apoptosis is a genetically regulated cell death involved in the deletion of cells in normal as well as malignant tissues. Inhibition of apoptosis or programmed cell death may be critical both in the development of cancer and in determining response to therapy. Apoptotic sensitivity is modulated by Bcl-2-related proteins through interactions between positively and negatively acting family members. It has been shown that the proteins of the bcl-2 gene family heterodimerize and homodimerize with each other and the relative proportions of these dimers may determine whether or not a cell becomes apoptotic. A hallmark of apoptosis is DNA degradation. Circulating DNA has generally been referred to as cell free DNA. In various pathologic conditions, qualitative and quantitative changes in circulating DNA have been shown. In this work, we studied the expression of Bcl-2, Bcl-xL and Bax and the serum DNA fragments in patients with primary squamous cell carcinomas of the larynx and their correlations with the clinicopathologic tumor parameters
Materials and methods: The study included 55 patients with primary laryngeal squamous cell carcinoma without distant metastasis. The expression of apoptosis related factors Bcl-2, Bcl-xL and Bax was studied by immunohistochemical staining of the biopsy specimens that were obtained before the administration of any treatment. Also, blood samples were taken to study the serum DNA fragments using cell death detection ELISA technique. Thirty five healthy males were chosen as a control group for serum DNA analysis matching in the ages with the 55 laryngeal carcinoma patients
Results: Twenty three cases [42%] were classified high Bax and 32 cases [58%] low Bax. High expression of Bax was associated with low T category, early clinical stage, low grade histology, negative lymph node metastasis and glottic location of tumors. Thirty cases [54.5%] were classified high Bcl-2 and 25 cases [45.5%] low Bcl-2. High Bcl-2 expression was associated with high grade histology, high T category, advanced clinical stage, positive regional lymph node metastasis and supraglottic location of tumors. Thirty three cases [60%] were classified high Bcl-xL and 22 cases [40%] low Bcl-xL. There was an inverse relation of Bcl-xL protein expression to the tumor histological grade as Bcl-xL expression decreased with decreasing tumor differentiation. Bcl-xL protein expression was negatively correlated with regional lymph node metastasis. No significant correlation was found between Bcl-xL expression and the parameters of tumor site, primary tumor size and clinical stage. There was a significant difference in concern to DNA fragmentation products among the studied laryngeal carcinoma patients with an increase in DNA fragmentation with increase in the tumor histological grade, primary tumor size and clinical stage of the tumor. The values of DNA fragmentation levels were significantly higher in patients with supraglottic tumors and also in patients with regional lymph node metastasis than without metastasis
In conclusion: the study of expression of apoptosis related proteins in tumor cells and the changes in serum DNA fragmentation may contribute to the prediction of prognosis of primary laryngeal carcinoma