Molecular differences between RER+ and RER- sporadic endometrial carcinomas in a large population-based series.
Studies, to date, have suggested that there are distinct molecular differences between microsatellite stable (RER(-)) and unstable (RER(+)) solid tumors, such as colorectal carcinoma. We investigated a range of molecular events including mutation frequency of K-ras, microsatellite instability within the coding region of TGF-beta RII, BAX, and IGF-IIR, loss of expression of p53, hMLH1, hMSH2, hMSH6, and PTEN, and methylation of hMLH1, hMSH2, and PTEN within a large population-based series of sporadic endometrial carcinomas to establish whether there are distinct differences between replication error repair (RER(+)) and RER(-) cases. RER(+) endometrial carcinomas tended to be diploid with normal p53 expression, compared with RER(-) cases. Mutations in TGF-beta RII, IGF-IIR, and BAX were rare, but there was a strong association between mutation and RER(+) status. Methylation and loss of hMLH1 expression were significantly more common in RER(+) cases, as was methylation of PTEN. K-ras mutations were equally frequent in RER(+) and RER(-) cases. Despite the absence of distinct clinicopathological differences between RER(+) and RER(-) cases in this series of sporadic endometrial carcinomas, our results confirm that there are molecular differences between RER(+) and RER(-) cases, but the molecular events occurring in RER(+) endometrial carcinomas differ from those seen in RER(+) colorectal carcinomas.
Macdonald
N D
ND
The Gynaecological Oncology Unit, St Bartholomew's and The London Hospitals, Queen Mary School of Medicine and Dentistry, Charterhouse Square, London, UK. ndmacdonald@hotmail.com
Salvesen
H B
HB
Ryan
A
A
Malatos
S
S
Stefansson
I
I
Iversen
O E
OE
Akslen
L A
LA
Das
S
S
Jacobs
I J
IJ
D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004260:DNA Repair; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins; D009687:Nuclear Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1