title: Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression.
abstract: Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8+TILs, higher CD8+/CD4+ratio, and higher PD-1+TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer. Of note, PD-L1 expression in tumor cells or immune cells was noted in all cases of CCOCs with MSI. These observations open an alternative therapeutic avenue for a fraction of patients with CCOC and argue for the routine testing of CCOCs for MSI, a test that is not currently routinely performed.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA.
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Howitt
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Strickland
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA.
authors.forename: Lynette M
authors.initials: LM
authors.lastname: Sholl
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA.
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Ritterhouse
authors.affiliation: Division of Genomic Stability and DNA Repair, Dana Farber Cancer Institute, Harvard Medical School , Boston, MA, USA.
authors.forename: Dipanjan
authors.initials: D
authors.lastname: Chowdhury
authors.affiliation: Division of Genomic Stability and DNA Repair, Dana Farber Cancer Institute, Harvard Medical School , Boston, MA, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
authors.affiliation: Medical Gynecologic Oncology Program, Dana Farber Cancer Institute, Harvard Medical School , Boston, MA, USA.
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.affiliation: Medical Gynecologic Oncology Program, Dana Farber Cancer Institute, Harvard Medical School , Boston, MA, USA.
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Konstantinopoulos
keywords: Clear cell ovarian cancer; PD-1; PD-L1; immunotherapy; microsatellite instability; tumor-infiltrating lymphocytes