title: Microsatellite analysis of hereditary nonpolyposis colorectal cancer-associated colorectal adenomas by laser-assisted microdissection: correlation with mismatch repair protein expression provides new insights in early steps of tumorigenesis.
abstract: Although microsatellite instability (MSI) testing is a useful tool for molecular screening of hereditary nonpolyposis colorectal cancer (HNPCC) carcinomas, conflicting results have been obtained in colorectal adenomas. This might result from different techniques of tissue sampling and MSI analysis. Alternatively, some HNPCC-associated adenomas may follow a molecular route that differs from the MSI pathway. In the present study we examined the MSI status of 18 adenomas from 17 HNPCC patients by comparing manual adenoma dissection under gross visual control with laser microdissection of single adenoma crypts. After manual gross dissection, 50% (9 of 18) and 11.1% (2 of 18) of the adenomas displayed high-level (MSI-H) and low-level (MSI-L) MSI, respectively. The same set of adenomas split into 83.3% (15 of 18) MSI-H and 5.6% (1 of 18) MSI-L after laser microdissection. The expression pattern of mismatch repair (MMR) proteins showed a higher concordance rate with the MSI status in laser-dissected (94%) than gross-dissected (47%) adenomas. Whereas two adenomas remained microsatellite stable (MSS) and MMR proficient even after laser-assisted dissection, two MSI-H cases showed either rare instabilities at coding microsatellites or intratumoral heterogeneity of MSI with and without MSH2 expression. This suggests that in some adenomas development of MMR dysfunction occurs stepwise with MSI, arising before complete loss of MMR gene expression, whereas other HNPCC-associated adenomas might develop independently of MMR deficiency.
authors.affiliation: Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giuffrè
authors.forename: Annegret
authors.initials: A
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Brodegger
authors.forename: Tina
authors.initials: T
authors.lastname: Bocker-Edmonston
authors.forename: Johannes
authors.initials: J
authors.lastname: Gebert
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Frank
authors.initials: F
authors.lastname: Kullmann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tuccari
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D000328:Adult; D000368:Aged; D020137:Base Pair Mismatch; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D004260:DNA Repair; D005260:Female; D006801:Humans; D007834:Lasers; D008297:Male; D042282:Microdissection; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D009363:Neoplasm Proteins