Immunohistochemical Screening for Mismatch Repair Protein Deficiency in Colorectal Cancer – MLH1and MSH2 Stains Are Contributory in 10% of Cases with Equivocal or Deficient Protein Staining
Sinead Deasy, Paul Ryan. Bon Secours Hospital, Cork, Ireland
Background: Current data supports prospective screening of all cases of colorectal cancer (CRC) for Lynch syndrome using mismatch repair protein immunohistochemistry (MMR IHC), often in conjunction with microsatellite instability testing. A 2-stain MMR IHC panel (MSH6/PMS2) has been reported as equal in efficacy to the typical 4-stain panel (MSH2/MSH6/MLH1/PMS2) with the added benefit of decreased cost. Prior to establishing a screening protocol in a hospital laboratory serving a population with high incidence of CRC the efficacy of each panel was compared.
Design: Archival tissue from 200 consecutive CRCs was stained with the 4 stain MMR IHC panel. Cases with equivocal or deficient staining were identified and the efficacy of 2 and 4 stain panels was compared. In addition, histologic features of cases with equivocal staining were noted.
Results: All 4 proteins were intact in 160 (80%) cases; MSH2 and MSH6 were both deficient in 5 (2.5%); and MLH1 and PMS2 were concordantly deficient in 24 (12%). One case each of isolated MSH6 and PMS2 deficiency was identified, and in eight cases one stain was equivocal but its dimer pair was either intact or deficient with four of these being equivocal MSH6 or PMS2. Only one case had both proteins of a dimer pair with equivocal staining. Overall, a 2-stain panel would have produced the same result as a 4-stain panel in 196/200 (98%) of all cases, and 36/40 (90%) of cases with abnormal MMR-IHC. The commonest histologic features noted in cases of equivocal staining was solid tumour/poor differentiation with prominent intraepithelial lymphocytes.
Conclusions: A 4-stain panel provides contributory data in a small minority of cases (2%) but is useful in most cases where a 2-stain panel produces an equivocal result. In choosing an MMR IHC panel laboratories must determine whether the additional cost of an up front 4-stain panel is justified or ameliorated by the need to maintain technical expertise and other costs of maintaining infrequently ordered stains.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 67, Tuesday Afternoon