15 Evaluation of Expression of the Bmi-1 Stem Cell Marker in Sinonasal Melanomas and Its Correlation With the Expression of Cell Cycle Proteins

Abstract

Sinonasal melanomas (SM) are rare neoplasias, and have distinct clinicopathological and molecular aspects of cutaneous melanoma. In cancer, a subset of neoplastic cells express proteins that are considered as stem cell markers (SC) such as Bmi-1 (B-cell-specific Moloney murine leukemia virus integration site 1). As Bmi-1 is a suppressor of the Ink4a/Arf locus, which encodes p16, it has been proposed that this interaction could lead to increased cell proliferation, affecting the biological behavior of the tumor. To assess the immunohistochemical expression of Bmi-1, p16 (tumor suppressor protein), and Ki-67 (present in proliferating cell) in SM, checking for Bmi-1, p16, and cell proliferation (Ki-67). Sixteen cases were analyzed semiquantitatively for the immunohistochemical expression of Bmi-1 and p16, and were classified as follows: absent, focal (<50% of cells), and diffuse (≥50%). The Ki-67 proliferative index was calculated by considering the number of positive cells in 1,000 analyzed. The expression of Bmi-1 was present in 6 cases (37.5%) and p16 in 11 cases (68.7%). The Ki-67 cell proliferation index ranged from 8% to 22%. Cell proliferation index was not related to Bmi-1 expression (17.3% in positive tumors vs 15% in negative tumors) or to p16 (13.06% in positive vs 16.35% in negative tumors). The high expression ratio of Bmi-1 and low ratio of p16 was noted in 3 cases. The loss of immunohistochemical expression of Bmi-1 was frequent, favoring the hypothesis that they presented molecular pathways different from the cutaneous counterpart. The expression levels of Bmi-1 and p16 did not correlate with each other or with the cell proliferative index, suggesting that the protein expression of these markers probably does not reflect their molecular functions.