Interobserver variability in the evaluation of mismatch repair protein immunostaining.
Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein staining. Full consensus was achieved in 51% of the stainings for MLH1, 61% for PMS2, 83% for MSH2, and 45% for MSH6. Weak stainings were the main cause of reduced consensus, whereas contradictory evaluations with normal as well as loss of staining were reported in 2% to 6% of the tumors. Interobserver variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance in hereditary nonpolyposis colorectal cancer, the interobserver variability identified highlights the need for quality assessment programs, including guidelines for classification of different expression patterns.
Klarskov
Louise
L
Department of Pathology, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark.
Ladelund
Steen
S
Holck
Susanne
S
Roenlund
Karina
K
Lindebjerg
Jan
J
Elebro
Jacob
J
Halvarsson
Britta
B
von Salomé
Jenny
J
Bernstein
Inge
I
Nilbert
Mef
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000378:metabolism*; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015588:Observer Variation; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes