Loss of mismatch repair protein immunostaining in colorectal adenomas from patients with hereditary nonpolyposis colorectal cancer

Abstract

Colorectal adenomas occur at younger age, at increased frequency and have a greater tendency for malignant transformation in patients with hereditary nonpolyposis colorectal cancer (HNPCC). We performed immunostaining for the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 in 35 colorectal adenomas from 26 patients with HNPCC and identified loss of immunostaining in 23/35 (0.66) adenomas. Loss of mismatch repair protein immunostaining was particularly frequent in large (45 mm) (14/16) and proximally located (13/15) adenomas, whereas the gene mutated-MLH1 or MSH2-and the type of mutation did not seem to affect the results. We conclude that loss of mismatch repair protein immunostaining is detected at a lower rate in adenomas than in carcinomas associated with HNPCC. Adenomatous tissue can thus be used for immunostaining of mismatch repair proteins in clinical investigations of HNPCC, but whereas loss of immunostaining may pinpoint the gene affected and thereby guide mutation analysis, retained staining cannot exclude that the adenoma developed as part of the syndrome due to reduced sensitivity. However, the analysis has a greater chance of being informative if large and proximally located adenomas are selected.

The added value of PMS2 immunostaining in the diagnosis of hereditary nonpolyposis colorectal cancer

“…1). Three tumors -one colon carcinoma and two adenomas -showed a MSS phenotype with retained immunostaining, which may, particularly for the adenomas, reflect that occasional HNPCC tumors escape identification with currently used methods, which identify defective MMR with a sensitivity of about 95% for carcinomas and 60-70% for adenomas 24 .…”

Deficient DNA Mismatch Repair Is Common in Lynch Syndrome-Associated Colorectal Adenomas

“…Finally, Halvarsson included 32 adenomas from 23 patients with a known germline mutation in MLH1 or MSH2, and an abnormal IHC result was observed in 66% of polyps. 30 No analysis of MSH6 was performed in any of these studies. If adenomas from patients with an MSH6 mutation are excluded from our analysis, then the sensitivity of a combined approach with MSI and IHC analyses rises to 78% in our study.…”

Colorectal Adenomas in Young Patients: Microsatellite Instability is not a Useful Marker to Detect New Cases of Lynch Syndrome

“…Consideration also must be given to the eventual limitations of current molecular and pathology techniques for examining adenomas when facing them as suspicious lesions for LS. 29 As proposed by Stoffel and Syngal, 14 any young patient diagnosed with one or more adenomas requires additional clinical as well as endoscopic evaluation for a better characterization.…”

“…However, loss of mismatch repair protein immunostaining is detected at a lower rate in adenomas than in HNPCC-associated CRC, especially when adenomas are small sized. 29 Another important issue to discuss is that we did not perform DNA MMR gene mutation analysis in all young patients with adenomas, but only in those who presented higher CRC risk, according to family history. It is possible, but highly improbable, that some of them who harbor stable lesions do in fact represent new cases of LS.…”