Surgical and Experimental Pathology (Mar 2019)
Evaluation of the expression of Bmi-1 stem cell marker in sinonasal melanomas and its correlation with the expression of cell cycle proteins
Abstract
Abstract Background Sinonasal melanomas (SNM) are aggressive neoplasms, which present distinct clinicopathological and molecular aspects when compared to cutaneous melanomas (CM). B-cell-specific moloney murine leukemia virus integration site-1 (Bmi-1) is a stem cell marker involved in the regulation of the cell cycle and has been found to be expressed in 70% of CM and 100% of benign nevi. Regarding the cell cycle, Bmi-1 is known to be an upstream repressor of p16, which is a tumor suppressor encoded by the INK4a/Arf locus. Considering this, the aim of this study is to evaluate the immunohistochemical expression of Bmi-1 in a series of SNM and its correlation with the expression of cell cycle proteins (p16 and Ki-67, a nuclear antigen of proliferating cells). Methods In 16 cases of SNM, nuclear expression of Bmi-1 and nuclear and cytoplasmic of p16 was classified as: absent, low (> 5 to < 50% of cells) and high (≥50%). Ki-67 proliferation index was represented by the ratio positive cells/ total cells. Results Histologically, all cases presented varying amount of necrosis and 75% contained undifferentiated cells. Bmi-1 was detected in 6 cases (37.5%) with high level of expression in 2; p16 expression was seen in 10 cases (62.5%) with high level in 7. The frequency of p16 expression did not differ significantly between tumors with or without Bmi-1 expression. Ki-67 index ranged from 8 to 22%. Neither Bmi-1 nor p16 expression showed correlation with Ki-67 index. Bmi-1 negative tumors presented more extensive necrosis (71.4%); no association between Bmi-1 expression and undifferentiated phenotype was observed. Conclusions In our SNM series, low immunohistochemical expression of Bmi-1 was a common phenomenon favoring the hypothesis that mucosal melanoma possibly presents molecular pathways different from the cutaneous counterpart. In SNM, Bmi-1 and p16 expression levels did not correlate with each other or with the cell proliferative index.
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