title: Chromosomal abnormalities and microsatellite instability in sporadic endometrial cancer.
abstract: Defective DNA mismatch repair and nonfunctional mechanisms controlling the proper progression of the cell cycle have been proposed as being responsible for the genomic instability and accumulation of karyotypic alterations in endometrial cancer (EC). To assess whether numerical chromosomal anomalies (aneuploidy) and microsatellite instability (MSI) might be representative of distinctive tumour behaviour, paraffin-embedded tissue samples from 86 patients with sporadic EC were evaluated by both fluorescence in situ hybridisation (FISH) and microsatellite analysis, using free nuclei and genomic DNAs (respectively). Approximately one-third of the tumours analysed (24/74; 32%) exhibited MSI, whereas 38/86 (44%) of the EC samples displayed aneuploidy. The majority of the unstable cases (15/24; 63%) were from advanced-stage patients. Conversely, 23 (61%) out of the 38 tumours with aneuploidy were from early-stage patients. No apparent correlation was found between MSI and aneuploidy, whereas the immunohistochemical (IHC) analysis revealed that inactivation of the MLH1 mismatch repair gene may be involved in the majority of the MSI+ sporadic ECs. No genetic or cytogenetic alteration analysed here seems to add any significant predictive value to the stage of disease.
authors.affiliation: Istituto di Genetica delle Popolazioni, C.N.R., Alghero, Maria La Palma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Muresu
authors.forename: M C
authors.initials: MC
authors.lastname: Sini
authors.forename: A
authors.initials: A
authors.lastname: Cossu
authors.forename: S
authors.initials: S
authors.lastname: Tore
authors.forename: P
authors.initials: P
authors.lastname: Baldinu
authors.forename: A
authors.initials: A
authors.lastname: Manca
authors.forename: M
authors.initials: M
authors.lastname: Pisano
authors.forename: C
authors.initials: C
authors.lastname: Loddo
authors.forename: S
authors.initials: S
authors.lastname: Dessole
authors.forename: A
authors.initials: A
authors.lastname: Pintus
authors.forename: F
authors.initials: F
authors.lastname: Tanda
authors.forename: G
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D020137:Base Pair Mismatch / Q000235:genetics; D002352:Carrier Proteins; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D014314:Trisomy
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1