Ki-67, CerbB-2, E-cadherin expressions in laryngeal cancer patients and the clinical significance of these biomarkers

AIM: There are various kinds of predictive and prognostic factors in laryngeal cancers in which smoking and alcohol together with ionizing radiation and genetic changes play role in its etiopathogenesis. These are principally related to the clinic, the pathology and the biology of the tumor. Amongst the biological factors, there are mainly some molecules such as tumor suppressor genes and oncogenes. In this present study, of these biological factors the relationships of E-cadherin, CerbB-2, Ki-67 expressions with clinicopathological variables of laryngeal cancer patients were investigated. E-cadherin is an adhesion molecule that provide to connections of intercellular areas and impairment of its expression provide a basis for development of the tumours. CerbB-2 is a tyrosine kinase growth factor and oncogene. CerbB-2 overexpression has been observed in the development of many malignant and therefore play a role in cell transformation and tumor pathogenesis. Ki-67 protein is a nuclear protein and is a marker of proliferation. For this reason Ki-67 is a good marker demonstrating cells in the growth fraction in normal and neoplastic tissues. The purpose of this study is to analyze the correlation between these biomarkers and the risk of cervical lymph node invasion, recurrence, distant metastasis and survival regarding the clinicopathological variables.MATERIALS AND METHODS: Forty-one patients with laryngeal carcinomas who were diagnosed and treated between 2009 and 2012 in Otolaryngology Department of Çanakkale Onsekiz Mart University Hospital were studied retrospectively. The clinical history, smoking and alcohol habits, age, gender, physical examination, involved anatomical region, and the tumour staging was recorded according to TNM classification. It was statistically evaluated the correlations between E-cadherin, Ki-67, CerbB-2 biomarkers expressions and tumor site and differentiation, and the risk of cervical lymph node metastasis, perineural, vascular and capsular invasion, as well as recurrence, and survival.RESULTS: The rate of cervical lymph node metastasis in supraglottic cancer patients, is statistically significantly higher than in patients with glottic cancer (p = 0,001). There was statistically significant correlation between T grade and the lowest survival rates (p=0,016). In addition we found statistically significant correlation between capsulary invasion and the lowest survival rates (p=0,007).There was no statistically significant correlation between E-cadherin, Ki-67, CerbB-2 proteins and the clinicopathological variables of the tumor such as localization, T stage, histopathological differentiation, cervical lymph node metastasis, perineural, vascular and capsular invasion, recurrence, ex and survival. A positive correlation between strong stain of the E-cadherin and Ki-67 proliferation index was determined (p=0.012).CONCLUSION:There was no statistically significant correlation between E-cadherin, Ki-67, CerbB-2?proteins and the clinicopathological variables of the tumor. This finding showed that these markers are not reliable prognostic and predictive factors for laryngeal cancers. A positive correlation between strong stain of the E-cadherin and Ki-67 proliferation index was determined. Loss of or reduction in E-cadherin expression has been associated with increased invasiveness, advanced T and N stages and unfavorable prognosis. Its expression was protected in well-differentiated and less invasive cancers, which maintain their cell-cell adhesions whereas it was reduced in undifferentiated cancers. This positive correlation between E-cadherin and Ki-67 proliferation shows us that histopathological differentiation of laryngeal cancers is maintained in spite of the high proliferation index.