Comparison of Colorectal and Endometrial Carcinoma in Patients with Lynch-Like Syndrome versus Patients with Lynch Syndrome

Blogger's Note: of interest to those with dual malignancies/mutation negative genetic testing...

abstract

 Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinoma identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathologic features of colorectal and endometrial carcinoma in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified
356/3352 (10.6%) patients with colorectal carcinoma and 72/215 (33%) patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%, p < 0.002). All patients with colorectal carcinomas demonstrating isolated loss of MSH6 expression had Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome-associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%, p = 0.04). There were no significant differences in clinicopathologic variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning for Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome-associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor.