Expression of the DNA mismatch repair proteins (hMLH1 and hMSH2) in infiltrating pancreatic cancer and its relation to some phenotypic features.
DNA mismatch repair system defects cause microsatellite instability (MSI) and form an alternative pathway in cancer development. Germline mutations of DNA mismatch repair genes account for hereditary nonpolyposis colorectal cancer, which has a different morphology and biology than sporadic cancers. MSI has also been found in sporadic neoplasms and some inflammatory conditions (chronic pancreatitis, ulcerative colitis). The purpose of the present study was to evaluate the expression of hMLH1 and hMLH2 proteins in infiltrating pancreatic cancer and to find out whether there is a relationship between some phenotypic manifestations and expression of MMR genes. We studied 30 cases of infiltrating pancreatic cancer and apart from hMLH1 and hMLH2 expression cytokeratin 7 and chromogranin were measured as markers of ductal and endocrine differentiation, respectively. All ductal pancreatic cancers expressed cytokeratin 7. In most cases the expression was strong, present in 50-100% of cells in moderately differentiated cancers and in 80-100% of cells in poorly differentiated cancers. Chromogranin expression was seen in 5 moderately differentiated cancers and in 6 poorly differentiated cancers (up to 20% of positive cells). In all cases DNA mismatch repair genes expression was present.


CONCLUSIONS
Ductal pancreatic carcinomas express hMLH1 and hMLH2 proteins irrespective of their differentiation. The expression of cytokeratin 7 is typical of ductal pancreatic carcinoma and its level is related to cancer differentiation. Some ductal pancreatic carcinomas irrespective of their differentiation show the expression of chromogranin, which is associated with the expression of hMSH2 gene.
Tomaszewska
Romana
R
Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Kraków.
Okoń
Krzysztof
K
Stachura
Jerzy
J
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins; D002864:Chromogranins / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D007633:Keratins / Q000096:biosynthesis; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009687:Nuclear Proteins; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002864:Chromogranins; D004268:DNA-Binding Proteins; C507497:KRT7 protein, human; D053552:Keratin-7; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D007633:Keratins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein