Genetic imbalances in endometrial hyperplasia and endometrioid carcinoma detected by comparative genomic hybridization.
OBJECTIVE
To evaluate the sequential genomic copy alterations related to the development of precursor lesions and endometrioid-type endometrial carcinomas, and its association with cellular atypia.


METHODS
Paraffin-embedded tissue specimens from 32 cases of endometrial hyperplasia, 15 of endometrial carcinoma, and 20 of normal endometrial tissue were retrospectively evaluated by the comparative genomic hybridization (CGH) technique. The average number of copy alterations (ANCA) index was used to define the incidence of genomic imbalances in each tissue group. Identified sequential genetic abnormalities were compared with the final histopathological diagnosis and the cellular atypia.


RESULTS
Detectable and consistent chromosomal imbalances were found in 13 hyperplasia and 9 carcinoma specimens. There was a significant correlation between ANCA value and degree of cellular atypia and tumor grade. While 1p36-pter, 20q deletions, and 4q overrepresentation were the most prevalent imbalances detected in both complex hyperplasia and complex atypical hyperplasia, 17q22-qter deletion and amplification of 2p34 were only seen in hyperplasia with atypical cells. Overrepresentations of chromosomes 8q, 1q, and 3q are the most frequent aberrations in endometrial carcinomas, but were absent from all the precursor lesions except one. Underrepresentations of chromosomes 1p36-pter and 10q are the other commonly seen aberrations in carcinomas, the latter being more frequent in moderately differentiated than in poorly differentiated lesions.


CONCLUSIONS
Different patterns of chromosomal aberrations are seen in precursor lesions than in endometrial carcinomas, except for the loss of 1p36-pter. The presence of 1p deletion in both endometrial hyperplasia and cancer specimens suggests that this is an early event in the development of carcinoma. These results support a stepwise mode of tumorigenesis with accumulation of a series of genomic copy alterations in endometrial carcinogenesis.
Muslumanoglu
Hamza M
HM
Department of Medical Genetics, Osmangazi University Medical Faculty, 26480 Eskisehir, Turkey.
Oner
U
U
Ozalp
S
S
Acikalin
M F
MF
Yalcin
O T
OT
Ozdemir
M
M
Artan
S
S
D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008875:Middle Aged; D009693:Nucleic Acid Hybridization