RESUMO
p27 and p57 are tumor suppressors that are dysregulated in many cancers. We investigated the immunohistochemical expression of p27 and p57 in ependymoma, with a secondary emphasis on cyclin D1, nestin, and Ki-67. Sixty-five patients diagnosed with ependymoma were included. Clinical and tumoral data were retrieved, and the expression of p27, p57, cyclin D1, nestin, and Ki-67 was measured. Pearson's χ2 test was used to measure associations and the Kaplan-Meier method was used for survival analysis. p27 underexpression was significantly associated with pseudopalisading necrosis in tumors with foci of necrosis (p = 0.004). Cyclin D1 overexpression was associated with intracranial (p = 0.044), recurrent (p = 0.022) and grade 3 tumors (p = 0.016); nestin overexpression was associated with supratentorial (p = 0.025), mitotically active (p < 0.001), and grade 3 tumors (p = 0.004); Ki-67 overexpression was associated with supratentorial (p = 0.044) and grade 3 tumors (p < 0.001) and the 3 main features of anaplasia. None of the markers were intercorrelated or predictive of overall survival. In conclusion, p27 underexpression in tumors with foci of necrosis signals a pseudopalisading pattern. Cyclin D1, nestin, and Ki-67 are useful markers in ependymoma, but evidence-based cutoff values are required to standardize this interpretation.
RESUMO
Women with endometrial carcinomas that express PD-L1 may respond better to immunotherapy. Our aim was to investigate the differential characteristics of PD-L1-positive endometrial carcinomas and the prognostic significance of PD-L1. We performed a retrospective chart review of 231 women with endometrial carcinomas who were managed at King Hussein Cancer Center (2007-2016) and performed immunohistochemistry for MLH1, PMS2, MSH2, MSH6, p53, and PD-L1. Overall, 89 cases (38.5%) were MMR-deficient. PD-L1 was expressed in 49 cases (21.2%) and its expression was significantly associated with MLH1/PMS2 deficiency (p = 0.044) but not MSH2/MSH6 deficiency (p = 0.59). p53 was mutant in 106 cases (46.5%), and its mutation was significantly associated with MMR proficiency (p < 0.001) but not PD-L1 expression (p = 0.78). In women with endometrioid adenocarcinomas, PD-L1 expression was significantly associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade (p = 0.008). Overall, PD-L1 expression did not significantly predict overall survival in unadjusted or adjusted analyses (p = 0.92 and 0.54, respectively). In conclusion, tumors with MLH1/PMS2 loss and high-grade endometrioid adenocarcinomas were more likely to express PD-L1 in tumor cells. Further research is required to investigate whether the presence of either characteristic signals a higher likelihood of a favorable response if immunotherapy is administered.
RESUMO
Central nervous system tumors in adolescents and young adults (AYA) are rarely reported in the literature. The association with cancer predisposition syndrome is not established. Programmed death ligand 1 (PD-L1) can predict the potential response of patients to immunotherapy. A link between mismatch repair protein deficiency (MMRP-D) and response to immunotherapy is established. P53 is reported to be positive in MMRD-D cases. We aim to investigate the frequency of MMRP-D in AYA with high-grade glioma and any potential association with PD-L1. A total of 96 cases were tested including 49 (51.0%) cases of glioblastoma. Six cases (6.25%) were MMRP-D, 17 (17.7%) were PD-L1 positive, mostly in grade IV tumors (8.7% in grade III compared to 26% in grade IV, p value = 0.027), and 69 (71.9%) were P3 positive. None of the MMRP-D cases expressed PD-L1. P53-positive cases were mostly MMRP proficient (n = 67; 74.4%, p value 0.051). Fourteen cases (28.7%) were positive for both PD-L1 and P53, while p53-positive grade IV tumors were mostly associated with negative PD-L1 (n = 29, 58%, p value = 0.043). MMRP deficiency does not appear to be prevalent in high-grade glioma in AYA. Expression of PD-L1 in a quarter of cases might suggest a role for immunotherapy in high-grade glioma.
