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Abstract
Introduction/Background Extensive cytoreductive surgery combined with chemotherapy is currently the standard treatment for high grade serous ovarian cancer (HGSOC). Yet, up to 80% of patients relapse, due to either platinum or PARP-inhibitor resistance. Recent preclinical data suggest that tumor-induced senescence (TIS) could play a pivotal role in chemo-resistance development. The primary endpoint of this study is to assess whether neoadjuvant chemotherapy (NACT) induces TIS and whether this phenotype can worsen the prognosis.
Methodology This is a retrospective cohort study conducted on HGSOC histologic specimens fixed in formalin and embedded in paraffin (FFPE), collected at Careggi University Hospital between May 2019 and January 202. Samples were collected during interval debulking surgery (group 1) or primary cytoreduction (group 2). Lipofuscin staining of stromal cells was used as immunohistochemistry (IHC) biomarker of TIS on FFPE samples. All FFPE’s results will be correlated with progression-free survival (PFS) using Cox proportional hazard regression. Univariate and multivariate analysis on clinical data of the two groups were performed.
Results Ten patients were enrolled in group 1 and nine in group 2. Lipofuscin staining was significantly more expressed in group 1 than in group 2 FFPE (50% vs 0%, p=0.0135). Univariate analysis showed that CA125 serum level at diagnosis was significantly higher in group 1 (p=0.0112), and PFS was longer in group 2 (p = 0.0012). At multivariate analysis, lipofuscin staining correlates with the CA 125 serum value at diagnosis (p = 0.041), PFS (p = 0.035) and relapse (p = 0.039).
Conclusion Our preliminary data demonstrate TIS development in HGSOC cells exposed to NACT, and this correlates with higher CA 125 at diagnosis, PFS and relapse. Further research on TIS in OC is needed to disclose its role in disease progression, and to identify suitable biomarkers for tailored treatment.