368 Can morphology and immune infiltration predict the HRD status in newly diagnosed high grade serous ovarian carcinoma? Lessons from the PAOLA-1/ENGOT-Ov25 Trial, a GINECO study

Introduction/Background A correlation between the morphology of high-grade ovarian serous carcinomas (HGOSC) and BRCA mutations has been previously reported (Soslow RA, Mod Pathol, 2012). Beyond BRCA, we studied the association between the morphology of HGOSC and the presence of homologous recombination deficiency (HRD). Methodology 522 on 806 cases of HGOSC from the PAOLA-1 clinical phase III trial were reviewed, including 163 cases with tumor BRCA mutation (tBRCAm), 345 cases without tumor BRCA mutation (tBRCAwt) and 14 cases with inconclusive BRCA tests. Regarding HRD status, 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD-) and 55 (10%) inconclusive. Morphological analysis included (i) tumor architecture (more than 25% of solid, endometrioid and transitional patterns defined a SET architecture), (ii) tumor-infiltrating intraepithelial lymphocytes (ieTILs), (iii) tumor stromal lymphocytes (sTILs), (iv) tumor necrosis, and (v) mitotic activity. Results SET architecture (51% vs 40%, p=0.02), high number of ieTILs (16% vs. 8%, p=0.007) and more than 10% of sTILs (27% vs 18%, p=0.02) were associated with tBRCAm compared to tBRCAwt tumors, mostly with tBRCA1m tumors. These criteria were also associated with HRD status, regardless of the tumoral BRCA mutation status: 54% vs 33% (pConclusion If the morphology of HGOSC correlates with HRD status and tBRCA status, it cannot substitute for molecular analysis as validated GIS score in daily practice. Disclosures See COI forms.