Molecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumors.
A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II non-endometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.
Abal
M
M
Unitat de Recerca Biomedica, Vall d'Hebron Research Institute University Hospital, Barcelona, Spain.
Planaguma
J
J
Gil-Moreno
A
A
Monge
M
M
Gonzalez
M
M
Baro
T
T
Garcia
A
A
Castellvi
J
J
Ramon Y Cajal
S
S
Xercavins
J
J
Alameda
F
F
Reventos
J
J
D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000502:physiology; D004260:DNA Repair; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human