Purpose: The Ohio State University was one of the first medical centers to begin routinely performing immunohistochemical staining for the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) on all newly diagnosed patients with colorectal cancer. The results of implementing this testing on a clinical basis are critically assessed.
Methods: From March 1, 2006, to March 31, 2008, 270 newly diagnosed colorectal cancer tumors received immunohistochemical staining for MLH1, MSH2, MSH6, and PMS2. If any stain was absent, the cancer genetic counselors were alerted, so that they could contact the patient. A follow-up genetic consultation was recommended for all patients with any stain absent other than MLH1 and to patients with absence of MLH1 +/- PMS2 who were diagnosed younger than 60 years had a multiple Lynch syndrome-associated cancers or had a first-degree relative with colorectal cancer or endometrial cancer. Those attending the genetic consultation were offered appropriate follow-up testing.
Results: There were 57 (21.1%) cases with abnormal immunohistochemical results. Genetics was able to contact 54 (94.7%) of these patients. It was determined that 34 (62.9%) of these 54 patients should be referred for a cancer genetics consultation, however, only nine (26.5%) made an appointment. Seven of the nine underwent additional testing, which was informative in five of the patients. Two (0.7%) new cases of Lynch syndrome were diagnosed and three patients were found to have proven/probable MLH1 promoter methylation.
Conclusions: Routine immunohistochemical of the mismatch repair proteins on all newly diagnosed patients with colorectal cancer can be implemented clinically, however, patient uptake of follow-up genetic consultation is lower than expected.