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Updated: Dec 31, 2025
Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
Immunohistochemical detection of senescence markers in human sarcomas
Alexandra Giatromanolaki1, Maria Kouroupi1, Konstantina Balaska1
1Departments of Pathology, Democritus University of Thrace and University General Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.
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 < 0.0001, r = 0.44) and with Lipofuscin expression (p = 0.02, r = 0.26).
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.
