In Lynch syndrome adenomas, loss of mismatch repair proteins is related to an enhanced lymphocytic response.
OBJECTIVE
Lynch syndrome-associated tumours are characterized by the presence of an increased number of tumour-infiltrating lymphocytes. This enhanced lymphocytic response may be elicited by genetically altered proteins that may arise as a result of a defective DNA mismatch repair system. The aim was to investigate this hypothesis by correlating loss of mismatch repair proteins and infiltration of lymphocytes in Lynch syndrome-associated adenomas and hyperplastic polyps.


RESULTS
Mismatch repair protein expression and the number of tumour-infiltrating lymphocytes were assessed in Lynch syndrome (41 adenomas and nine hyperplastic polyps) and in familial colorectal cancer (nine adenomas and one hyperplastic polyp). Nineteen sporadic adenomas were included as a control group. Twenty of 32 (63%) adenomas with loss of mismatch repair protein expression showed an increase in tumour-infiltrating lymphocytes. Eight adenomas (8/32; 25%) displayed many tumour-infiltrating lymphocytes, whereas most adenomas (12/32; 38%) showed a minor increase. In adenomas with mismatch repair protein expression, both sporadic and Lynch syndrome associated, not one showed an increased number of tumour-infiltrating lymphocytes. Hyperplastic polyps in Lynch syndrome patients showed neither loss of mismatch repair expression nor an increase in tumour-infiltrating lymphocytes.


CONCLUSIONS
There is a correlation between the loss of mismatch repair proteins and the infiltration of lymphocytes in Lynch syndrome-associated adenomas.
Meijer
Tineke W H
TW
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Hoogerbrugge
Nicoline
N
Nagengast
Fokko M
FM
Ligtenberg
Marjolein J L
MJ
van Krieken
J Han J M
JH
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D004273:DNA, Neoplasm; 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