Clear cell "sugar" tumor is a rare benign neoplasm arising in the lung, considered as a part of the PEComa family. As PEComas of other sites, this tumor expresses melanocytic markers such as HMB45 and Melan-A. Despite cathepsin K, MITF and CD68 staining are known to be positive in a large number of PEComas and TFE3 rearrangement has been reported in a subset of PEComas, no data is available regarding the expression of these markers and the occurrence of TFE3 and TFEB rearrangement in clear cell "sugar" tumor of the lung. We have investigated the immunolabeling of cathepsin K, MITF, and CD68 in five cases of clear cell "sugar" tumor. Moreover, we have also sought the presence of TFE3 and TFEB rearrangement by fluorescence in situ hybridization (FISH) assay. In all tumors, strong immunoreactivity of cathepsin K and CD68 (PG-M1 and KP1 clone) was demonstrated, whereas none of them labeled for MITF staining and showed TFE3 or TFEB rearrangement. These findings widen the immunohistochemical profile of clear cell "sugar" tumor providing useful new markers for challenging cases. The expression of lysosomal markers, such as cathepsin K and CD68, strengthens the hypothesis that this tumor is part of the PEComa family.
Triple-negative breast carcinomas represent a tumor group of pivotal clinical importance given the lack of target therapies. The prognostic significance of triple-negative breast carcinomas remains unclear because of their histological and molecular heterogeneity. Currently, neither prognostic nor predictive factors are available for these tumors. Retinoblastoma (Rb) pathway loss has been linked to clinical outcome in various cancer types, including breast cancer. We investigated the association between Rb and p16 protein expression and clinical outcome in no-special-type triple-negative breast carcinomas. Immunohistochemical staining for Rb, p16, p53 and CK5 was carried out on a section from archival specimens of 117 no-special-type triple-negative breast carcinomas. Immunopositive p16 (p16 þ ) and immunonegative Rb (Rb À ) staining were seen in 49.5% and in 24.8% of tumors, respectively. There was an inverse correlation between p16 þ and Rb À (Po0.001). P16 þ was correlated with G3 grade (Po0.001), high Ki-67 (P ¼ 0.03), p53 overexpression (Po0.001) and CK5 immunopositivity (P ¼ 0.01). Rb À was not associated with any clinicopathologic variable. Follow-up and therapy data were available in 95 patients. In 20 patients treated with surgery only, neither p16 þ nor Rb À immunostaining were associated with disease-free survival and overall survival. In 75 patients treated with adjuvant chemotherapy, p16 þ was associated with good response to therapy with significant increased disease-free survival (P ¼ 0.001) and showed a trend towards a statistical significance for increased overall survival (P ¼ 0.056); Rb À were not associated with disease-free survival and overall survival. In multivariate analysis, p16 þ was independently associated with disease-free and overall survival, with a hazard ratio of 0.18 (95% CI: 0.06-0.51; P ¼ 0.001) and 0.21 (95% CI: 0.06-0.74; P ¼ 0.015), respectively. In patients with no-specialtype triple-negative breast carcinomas, p16 þ is related to good response to adjuvant chemotherapy and can be considered the best surrogate marker for Rb pathway loss.
BackgroundThe aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery.MethodsClinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between ‘pure’ or ‘mixed’ histology ILC and Ki67.ResultsAt a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8 %, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21 %); 10-years DFS and OS were 75.1, 66.5, and 30.2 % (p = 0.01) and 84.3, 76.4 and 59 % (p = 0.003), for patients with a Ki67 < 6 %, between 6 and 21 %, and >21 %, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85 %, OS 100 %). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with ‘pure’ ILC performed worse than ‘mixed’ histology.ConclusionsDespite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with ‘pure’ ILC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0325-z) contains supplementary material, which is available to authorized users.
STING is a molecule involved in immune reactions against double-stranded DNA fragments, released in infective and neoplastic diseases, whose role in the interactions between immune and neoplastic cells in clear cell renal cell carcinoma has not been studied yet. We investigated the immunohistochemical expression of STING in a series of 146 clear-cell renal cell carcinomas and correlated it with the main pathological prognostic factors. Furthermore, tumoral inflammatory infiltrate was evaluated and studied for the subpopulations of lymphocytes. Expression of STING was observed in 36% (53/146) of the samples, more frequently in high-grade (G3–G4) tumors (48%,43/90) and recurrent/metastatic ones (75%, 24/32) than in low grade (G1–G2) and indolent neoplasms (16%, 9/55). STING staining correlated with parameters of aggressive behavior, including coagulative granular necrosis (p = 0.001), stage (p < 0.001), and development of metastases (p < 0.001). Among prognostic parameters, STING immune expression reached an independent statistical significance (p = 0.029) in multivariable analysis, along with the stage and the presence of coagulative granular necrosis. About tumor immune-environment, no significant statistical association has been demonstrated between tumor-infiltrating lymphocytes and STING. Our results provide novel insights regarding the role of STING in aggressive clear cell renal cell carcinomas, suggesting its adoption as a prognostic marker and a potentially targetable molecule for specific immunotherapies.
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