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EP814 TGFβ pathway activation is a predictor of progression free and overall survival in advanced high-grade serous ovarian cancer according to the surgical aggressiveness and rate of cytoreduction of different oncologic centers
  1. L Ceppi1,
  2. T Grassi1,
  3. C Romualdi2,
  4. P Di Lorenzo1,
  5. S Palazzi1,
  6. E Biagioli3,
  7. A Garbi4,
  8. L Paracchini3,
  9. F Landoni1,
  10. GD Aletti4,5,
  11. N Colombo4,6,
  12. R Fruscio1,
  13. S Marchini3 and
  14. M D’Incalci3
  1. 1Milano Bicocca University, San Gerardo Hospital, Monza
  2. 2Department of Biology, University of Padova, Padova
  3. 3Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS
  4. 4Division of Gynecologic Oncology, European Institute of Oncology
  5. 5University of Studies of Milan, Department of Oncology and Hemato-oncology
  6. 6Department of Medicine and Surgery, Milano Bicocca University, Milan, Italy


Introduction/Background The activation of TGFβ pathway in advanced stage high-grade serous ovarian cancer (HGSOC) has been found to be related to short progression free survival (PFS) and overall survival (OS). miRNA181a-5p was found to be a proxy of TGFβ activation. This prognostic role has been identified only in cohorts with low surgical complexity, we evaluated 2 cohorts with different surgical approaches.

Methodology Series of HGSEOC from two centers (European Institute of Oncology, Milan, Cohort1; San Gerardo Hospital, Monza, Cohort2) were analyzed for clinical features and miRNA quantification to test their prognostic value using a Cox-proportional hazard regression model.

Results 118 and 84 patients were included, respectively. Cohort1 versus Cohort2 was composed of similar FIGO stages, higher upper abdominal disease spread (UAD) (P<0.001), higher complexity score (CS) of 6.7±2.4 and 3.5±1.7 (P<0.001) and lower residual tumor (P<0.001). Cohort1 compared to Cohort2 was associated with a lower number of events of PFS and OS (P<0.0012).

An optimized threshold of miR181a-5p expression to segregate patients according to their prognosis was identified (miR-low and miR-high): for Cohort1 no threshold was reached; for Cohort2 a threshold segregated PFS of 20.9 v. 9.6 months (P:0.0008) and OS of 60.3 v. 23.3 months (P:0.0008), respectively.

In multivariate analysis, no significance was observed for miR-high in Cohort1. For Cohort2, miR-high was related to worse PFS (P:0.0002), and OS (P:0.007).

Conclusion miR181a-5p was observed as a prognostic biomarker in HGSEOC in Cohort2, -less aggressive surgery-, instead no prognostic role was observed in Cohort 1 -aggressive surgery-. This question-generating analysis suggests that TGFβ activation, a proxy of tumor aggressiveness, might be withdrawn by an aggressive surgical approach.

A prospective validation of miR181 role is needed, the translational ancillary study of the TRUST trial (NCT # 02828618) may answer this question.

Disclosure Nothing to disclose.

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