Abstract

Laryngeal squamous cell carcinoma (SCC) is the most frequent tumor of head and neck region. Survivin (SVV) is one of the inhibitors of apoptosis which is over-expressed in almost all malignancies but rarely detected in normal differentiated adult tissues. Bcl-XL and Bax are members of a family of proteins that regulate apoptosis. In contrast to Bcl-XL that inhibits apoptosis over-expression of Bax protein accelerates the programmed cell death (apoptosis). Aims: We used immunohistochemistry to investigate a potential role of SVV as an early predictor of malignant transformation in precancerous lesions of the larynx and in the progression of laryngeal SCC in comparison with the expression of Bcl-XL and Bax in laryngeal SCC. We also aimed to analyze the relationships between the expression of SVV, Bcl-XL and Bax and some prognostic factors including site, histological grade, clinical staging (depth of tumor invasion) and lymph node metastasis. Patients & Methods: This study included 6 normal laryngeal mucosae, 7 dysplastic laryngeal epithelia, 5 in situ laryngeal carcinomas, and 32 resected laryngeal SCC. Clinical evaluation was done. Specimens were formalin-fixed, paraffin-embedded, stained with H&E, classified and graded according to WHO classification, (2005) and immunostained to detect Survivin and Bcl-XL and Bax proteins using the avidin-biotin peroxidase method. Results: Survivin expression gradually increased significantly with advance of laryngeal carcinoma through the sequence of dysplasia, in situ carcinoma and infiltrating carcinoma (P<0.04). There is a statistically significant increase in Survivin expression with increasing tumor grade (P<0.03) and with advance in clinical staging (depth of tumor invasion) (P<0.01). Regarding lymph node metastasis SVV was more expressed in laryngeal SCC exhibiting lymph node metastasis (P<0.02). Bax expression was decreased significantly in infiltrating laryngeal carcinoma (P< 0.04) compared with pre-malignant lesions of the larynx.  In contrast, Bcl-XL was increased significantly with the advance of laryngeal carcinoma through dysplasia, carcinoma sequence (P< 0.02). There was no statistically significant difference in either Bcl-XL or Bax expression considering tumor differentiation, advanced clinical staging (depth of tumor invasion) or lymph node metastasis. Conclusion: Survivin plays an important role in the progression of laryngeal SCC towards higher grades, invasion and metastasis. Bcl-XL and Bax play their role in early stages of laryngeal epithelial transformation but have nothing to do as the tumor progresses to higher grades, infiltrates deeply, or giving lymph node metastasis