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Background/aim The role of senescence in defining tumor aggressiveness at a clinical level remains obscure. A novel mixed histochemical/immunohistochemical method (SenTraGor™, STG) detecting lipofuscin accumulation allows the assessment of senescent cells in paraffin-embedded tissue material. Materials and methods STG expression was quantified in 98 surgically resected primary non-small-cell-lung carcinomas (NSCLC). Data were analyzed in parallel with other immunohistochemical markers related to hypoxia and autophagy. Results Strong STG staining was noted in 36/98 cases (36.7%). High STG expression was significantly associated with high HIF1α expression and high expression of glucose (GLUT1) and monocarboxylate (MCT2) transporters, pointing to a link between senescence, hypoxia and glycolysis. High STG expression was also linked with high cytoplasmic accumulation of MAP1-LC3B, TFEB and LAMP2a, suggestive of a blockage of autophagy flux in tumors with intense senescence. Survival analysis showed a direct association with poor survival, independently of stage. Conclusion SenTraGor™ provides a reliable methodology to detect lipofuscin accumulation in cancer cells in paraffin-embedded tissues, opening a new field for translational studies focused on senescence.

Background. The interpretation of histopathological changes of endometrial hyperplasia with or without atypia can be challenging. We aim to investigate the role of specific immunohistochemical markers in the endometrial stroma to classify endometrial hyperplasia in difficult cases. Methods and Results. We retrospectively reviewed and reclassified (WHO 2014): 47 specimens with endometrial hyperplasia without atypia, 33 with atypical hyperplasia (AH), and 13 endometrioid adenocarcinomas. We performed IHC for B-catenin, E-cadherin, p16, estrogen receptors and progesterone receptors, and B-cell lymphoma 2 (BCL2). Percentage of positive stromal cells was calculated. B-catenin was equally expressed in the stroma of both hyperplasia and AH (mean 60%, 50%; P = .17) and was absent from adenocarcinoma (0%, hyperplasia vs adenocarcinoma; P

Tumor-draining lymph nodes (TDLNs) are critical organs, where activation of B cells and T cells is orchestrated. Effector or regulatory anti-tumor immune responses are reflected by the composition of the lymphocytic and monocytic cell population of the node. Aside from the migratory cancer cell abilities, immune cell phenotypic changes in the TDLNs may define nodal invasion by cancer. We assessed the qualitative and quantitative differences between lymphocytic phenotypes in regional TDLNs, in 20 node-negative and 20 node-positive patients (involved and uninvolved nodes) with rectal adenocarcinomas. Benign reactive nodes were also analyzed. CD8+ cells, the main source of cytotoxic T cells, were increased in all TDLNs and, even stronger, in the involved nodes. The percentage of CD4+ cells were significantly increased in negative and uninvolved nodes, while the CD4/CD8 ratio was significantly lower in involved TDLNs. CD25+ and FOXP3+ regulatory lymphocytes, however, prevailed in involved nodes, while uninvolved and negative nodes had a low presence of these regulatory cells. CD20+ B cells were also more abundant in involved nodes. PD-1+ lymphocytes were localized in the germinal centers. A significantly lower percentage of PD-1+ lymphocytes were noted in involved nodes. The development of a regulatory lymphocytic phenotype in the TDLNs appears as an important mechanism that allows cancer cell installation into the nodal environment. As negative/uninvolved TDLNs had a less severe immunosuppression, it is postulated that secreted molecules by cancer cells gradually attenuate the anti-tumor defenses of the TDLNs allowing the subsequent intra-nodal growth of cancer.

Introduction Senescent cells in tumors are not inert cells but exert bystander effects by developing secretory phenotypes affecting the extracellular matrix and interfering the biological behavior of adjacent tumor cells. Materials and Methods We assessed putative senescent cell content in a series of human sarcomas, using in parallel markers related to cell proliferation (Ki67), DNA damage (γH2Ax), lipofuscin detection (SenTraGor®) and two cyclin-dependent kinase CDK-inhibitors (p16/INK4a and p21/cip/waf21). Results Necrosis was directly linked with the size of tumors (p = 0.02, r = 0.25), number of mitosis (p = 0.05, r = 0.21) and inversely with the expression of γH2Ax (p = 0.01, r = 0.28). Smaller tumors (less than 3 cm) had a higher p16 expression (p = 0.07); Moreover, in group analysis, tumors with lack of expression of p16 had significantly higher necrosis score (p = 0.03). Linear regression analysis showed that p21 expression was strongly and directly related with MIB1 (p Conclusion Senescence markers are extensively expressed in human sarcomas and correlated with histopathological features. However, p16, p21 and Lipofuscin expression show different patterns, suggesting that these markers may detect different senescence phenotypes. In addition, our data suggest that the novel marker SenTraGor® may detect phenotypes of senescent cells involving p21 activation.