If looks could kill: morphologic subtypes of high-grade serous ovarian cancer.

Despite similar histologic appearance amongst high-grade serous ovarian cancers (HGSOC), anecdotally there are differences in gross appearance. However, no systematic framework to classify morphologic differences exists. Therefore, we aimed to determine whether high-grade serous ovarian cancers (HGSOC) can be reliably divided into distinct gross morphologic subtypes and to assess clinical outcomes and molecular features of these subtypes. A retrospective review was performed of video-recordings from patients who underwent laparoscopic assessment of disease burden prior to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). Video recordings were reviewed by at least 2 physicians. A total of 4 sites (diaphragm, omentum, peritoneum, and pelvis) were assessed and classified as type I (deep, infiltrative disease with distortion of surrounding tissue) or type II (superficial, exophytic disease bordered by normal tissue). Tumor tissues from 16 of these chemotherapy-naïve patients were analyzed by multi-platform omics (RNA sequencing, proteomics). Clinical outcomes were assessed utilizing a prospectively collected database and compared by morphology using t-test or Fisher's exact test. Of the 99 evaluable patients, 60 exhibited uniform morphology at all involved metastatic sites (65% type I and 35% type II), and 81 exhibited a predominating morphology (58% type I and 42% type II). A total of 164 images were reviewed by a third physician with 83.5% inter-rater concordance (κ=0.6446). Patients with uniform type 1 (n=34)tumor morphology were more likely to exhibit an excellent response to NACT (defined as radiologic or CA-125 complete response) than those with type II (n=16) tumor morphology (47% vs 18%, p=0.13). Patients with type II predominant tumor morphology had a significantly higher estimated blood loss at the time of interval debulking surgery (p=0.008) as well as longer operative time (p=0.03) compared with type I tumor morphology. Patients with complete type II morphology were more likely to have a modified Fagotti score of <8 (p=0.026), and thus were more likely to be triaged to PDS. On histopathologic review of 7 type I cases and 4 type II cases, no obvious histo-pathological pattern dominated either type. We identified distinct molecular differences between the 2 types, including increased TGF-β expression in type I and increased MYC expression in type II. Type I tumors seem to have abundant stroma and are immunologically active, whereas type II tumors seem to be dominated by cancer cells, have little stroma, and are immunologically cold. There are at least two distinct gross morphological patterns of HGSOC with unique molecular differences and responses to chemotherapy. These findings could have major clinical implications for tailored therapeutic strategies. [Display omitted] [ABSTRACT FROM AUTHOR]