Loss of mismatch repair protein immunostaining in colorectal adenomas from patients with hereditary nonpolyposis colorectal cancer.
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 (>5 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.
Halvarsson
Britta
B
Department of Pathology, Lund University Hospital, Lund, Sweden. Britta.Halvarsson@pat.lu.se
Lindblom
Annika
A
Johansson
Leif
L
Lagerstedt
Kristina
K
Nilbert
Mef
M
D048868:Adaptor Proteins, Signal Transducing; D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000032:analysis; D000328:Adult; D000368:Aged; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000378:metabolism / Q000473:pathology*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; 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; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene 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