Early recognition of patients at risk for Lynch syndrome is critical but often difficult.
Recently, a predictive algorithm—the PREMM model—has been developed to quantify the risk of carrying a germline mutation in the mismatch repair genes MLH1 and MSH2.
However, the model's performance in an unselected, population-based colorectal cancer population as well as its performance in combination with tumor mutation in the mismatch repair testing are unknown.
Dr Francesc Balaguer and colleagues from Spain included all colorectal cancer cases from the EPICOLON study, a prospective, multicenter, population-based cohort.
|The PREMM model with a 5% cut-off had a sensitivity of 100%|
All patients underwent tumor microsatellite instability analysis, and immunostaining for MLH1 and MSH2.
Those with mutation in the mismatch repair deficiency underwent tumor BRAF, V600E mutation analysis, and MLH1/MSH2 germline testing.
The researchers found that the PREMM model with a 5% cut-off had a sensitivity, specificity, and positive predictive value of 100%, 68%, and 2%, respectively.
The team observed that the use of a higher PREMM cut-off provided a higher specificity and positive predictive value, at expense of a lower sensitivity.
The combination of a 5% cut-off with tumor mutation in the mismatch repair testing maintained 100% sensitivity with an increased specificity and positive predictive value.
The positive predictive value of a PREMM score of 20% alone approached the positive predictive value obtained with PREMM score of 5% combined with tumor mutation in the mismatch repair testing.
The team assessed that in addition, a PREMM score less than 5% was associated with a high likelihood of a BRAF V600E mutation.
Dr Balaguers' team concluded, "The PREMM model is useful to identify MLH1/MSH2 mutation carriers among unselected colorectal cancer patients."
"Quantitative assessment of the genetic risk might be useful to decide on subsequent tumor mutation in the mismatch repair, and germline testing."