Lynch Syndrome from a surgeon perspective: retrospective study of clinical impact of mismatch repair protein expression analysis in colorectal cancer patients less than 50 years old
1 Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy
2 Department of Pathology, Brescia University, Brescia, Italy
3 Genetic and Biology, Department of Biomedical Sciences and Biotechnologies, Brescia University, Brescia, Italy
BMC Surgery 2014, 14:9 doi:10.1186/1471-2482-14-9Published: 17 February 2014
In clinical practice, unexpected diagnosis of colorectal cancer in young patients requires prompt surgery, thus genetic testing for Lynch Syndrome is frequently missed, and clinical management may result incorrect.
Patients younger than 50 years old undergoing colorectal resection for cancer in the period 1994-2007 were identified (Group A, 49 cases), and compared to a group of randomly selected patients more than 50 (Group B, 85 cases). In 31 group A patients, immunohistochemical expression analysis of MLH1, MSH2 and MSH6 was performed; personal and familial history of patients with defective MMR proteins expression was further investigated, searching for synchronous and metachronous tumors in probands and their families.
Fifty-one percent of patients did not express one or more MMR proteins (MMR-) and should be considered Lynch Syndrome carriers (16 patients, group A1); while only 31.2% of them were positive for Amsterdam criteria, 50% had almost another tumor, 37.5% had another colorectal tumor and 68% had relatives with colorectal tumor. This group of patients, compared with A2 group (< 50 years old, MMR+) and B group, showed typical characteristics of HNPCC, such as proximal location, mucinous histotype, poor differentiation, high stage and shorter survival.
The present study confirms that preoperative knowledge of MMR proteins expression in colorectal cancer patients would allow correct staging, more extended colonic resection, specific follow-up and familial screening.