PATH-59. HISTOPATHOLOGICAL INVESTIGATION OF THE 1p/19q-CODELETED GLIOMAS RESECTED FOLLOWING ALKYLATING AGENTS CHEMOTHERAPY

BACKGROUND Little is known about histopathological changes after chemotherapy in lower-grade gliomas (LrGGs). METHODS We investigated 15 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agents chemotherapy in comparison with their pre-chemotherapy specimens. Histopathological changes by chemotherapy were evaluated by hematoxilyn-eosin staining and immunohistochemistry for Ki-67/MIB-1, CD68 as pan macrophage/monocyte marker, CD163 as presumed marker of M2 polarity, and nestin and CD133 as markers of glioma stem cells (GSCs). RESULTS Histologically, there were several presumed chemotherapy-related changes in the post-chemotherapy specimens, with the most frequent findings being sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 indices significantly decreased, and CD68+ cells significantly increased after chemotherapy. The increasing rate of CD68+ cells in the post-/pre-chemotherapy specimens was prone to be associated with patients’ progression-free survival (PFS) and overall survival (OS), but not tumor response. The number of CD163+ cells and the ratio of nestin+ cells and CD133+ cells significantly increased after chemotherapy. The number of CD163+ cells, the ratio of nestin+ cells and CD133+ cells, and M2 (CD163+)/M1+M2 (CD68+) ratio in the post-chemotherapy specimens were negatively correlated with patients’ PFS and OS. There was no difference between chemotherapy regimens (temozolomide versus nitrosourea-based) in the number of CD163+ cells and the ratio of nestin+ and CD133+ cells. CONCLUSIONS GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agents chemotherapy in LrGGs.