As expected, the highest level of MSI-high was seen in small bowel cancer (25%), followed by endometrial, colorectal, and gastric cancer (16%, 14%, and 6%, respectively), Dr. Stadler said.
“High frequency MSI was also seen in a number of other tumors as suggested by other papers previously,” she noted.
LS was present in 16.3% of MSI-high tumors vs. 1.9% of MSI-indeterminate (moderate MSI level) tumors, and 0.3% of microsatellite stable (MSS) tumors, she added.
Additional tumor evaluations, including immunohistochemical staining for the mismatch repair genes, were also performed.
“Our analysis corroborated the finding that in these Lynch patients, the MSI-high and MSI-indeterminate tumors were caused by Lynch Syndrome. This is in contrast to our Lynch Syndrome patients with microsatellite stable tumors; their tumor signature suggested that the Lynch Syndrome did not cause these cancers,” she said. “In fact, the prevalence of Lynch Syndrome in the MSS cohort of 0.3% is equivalent to the presence of Lynch Syndrome in the general at-large population.”
Of note, 50% of LS patients with MSI-high and indeterminate tumors had cancers other than colorectal or endometrial cancer, including prostate, sarcoma, mesothelioma, adrenocortical carcinoma, and ovarian germ cell carcinoma, which have been rarely or not previously associated with LS, and 45% of those patients did not meet clinical testing criteria for LS and would not have undergone LS testing.
This finding underscores the previously unknown heterogeneity of the phenotype.