Alexandra Giatromanolaki1, Maria Kouroupi2, Konstantina Balaska2, Michael I Koukourakis3. 1. Department of Pathology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece agiatrom@med.duth.gr. 2. Department of Pathology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 3. Department of Radiotherapy/Oncology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Abstract
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. Copyright
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. Copyright
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