Patients with endometrial cancer and high microsatellite instability demonstrated an increased expression of granzyme B, indicating cytotoxic T lymphocyte activation, according to analysis of data from The Cancer Genome Atlas presented at Society of Gynecologic Oncology Annual Meeting.
These findings suggest that immune checkpoint inhibition should be studied in women harboring these tumors, according to the researchers.
Colorectal and gastric cancers with microsatellite instability (MSI) tumors appear more responsive to immunotherapy than microsatellite stable (MSS) tumors, according to study background.
, MD, gynecologic oncology fellow at The University of Texas MD Anderson Cancer Center, and colleagues evaluated archived tumor bank specimens from The Cancer Genome Atlas to evaluate gene expression in high-MSI (MSI-H) endometrial cancers.
Pakish and colleagues matched 118 MSI-H endometrial cancers to 160 MSS tumors by grade, stage, age and BMI. They conducted immunohistochemistry analyses on formalin-fixed paraffin embedded endometrial cancer samples, using a multiplex staining system with anti-granzyme B antibodies for cytotoxic T lymphocytes.
The researchers found that tumors with high MSI showed an overall activation of the granzyme B signaling pathway compared with MSS tumors (P = .002), as well as an upregulation of granzyme B.
Further, among 37 MSI-H tumors, including in the immunohistochemistry analysis, 32 (86%) showed a loss of MLH1 by promoter methylation, whereas five (14%) were identified as Lynch syndrome carriers.
No significant differences in age, disease stage or grade, or BMI persisted between groups.
Tumors with high MSI exhibited a nonsignificant positive intratumoral staining for granzyme B compared with MSS tumors (1.12% vs. 0.62%).
“Based on our findings, we will initiate an MSI-stratified clinical trial of immune checkpoint inhibition,” Pakish and colleagues wrote. “Additional studies are also ongoing using a large panel of immune cell markers to further investigate differences in the immune microenvironment of high MSI endometrial cancers compared to MSS cancers.” – by Cameron Kelsall
Pakish JB, et al. Abstract 5. Presented at: Presented at: Society of Gynecologic Oncology Annual Meeting; March 19-22, 2016; San Diego.
Today could not confirm the researchers’ relevant financial disclosures at the time of reporting.