TY - JOUR
T1 - High frequency of RASSF1A and RARb2 gene promoter methylation in morphologically normal endometrium adjacent to endometrioid adenocarcinoma
AU - Arafa, M
AU - Kridelka, F
AU - Mathias, V
AU - Vanbellinghen, J-F
AU - Renard, I
AU - Foidart, J-M
AU - Boniver, J
AU - Delvenne, P
PY - 2008/11
Y1 - 2008/11
N2 - AIMS: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis.METHODS AND RESULTS: Archival biopsy specimens of 39 EECs, 14 cases of atypical hyperplasia (AH), 11 histologically normal endometrial tissues adjacent to EECs and 24 normal control endometrial samples were retrieved. The cases were tested by quantitative methylation-specific polymerase chain reaction with primers hybridizing in the promoter regions of five genes frequently methylated in human cancer (RASSF1A, RARb2, P16, MGMT and GSTPi). Twenty-nine of 39 (74%) EECs and 7/14 (50%) AHs were methylated for the RASSF1A gene, whereas 17/39 (44%) EECs and 6/14 (43%) AHs were positive for the methylation of the RARb2 gene. No significant results were obtained for the other genes (P16, MGMT and GSTPi). Interestingly, 4/11 (36%) and 6/11 (55%) histologically normal endometrial tissues adjacent to EEC showed, respectively, RASSF1A and RARb2 gene methylation. Furthermore, these 11 specimens were microsatellite stable and showed similar proliferative, cell cycle and apoptotic mean labelling indices as the normal endometrial control tissues.CONCLUSIONS: Promoter region methylation of RASSF1A and RARb2 genes is an early event in endometrial carcinogenesis.
AB - AIMS: To identify a DNA methylation signature of endometrioid carcinoma of the endometrium (EEC) in the early stages of endometrial carcinogenesis.METHODS AND RESULTS: Archival biopsy specimens of 39 EECs, 14 cases of atypical hyperplasia (AH), 11 histologically normal endometrial tissues adjacent to EECs and 24 normal control endometrial samples were retrieved. The cases were tested by quantitative methylation-specific polymerase chain reaction with primers hybridizing in the promoter regions of five genes frequently methylated in human cancer (RASSF1A, RARb2, P16, MGMT and GSTPi). Twenty-nine of 39 (74%) EECs and 7/14 (50%) AHs were methylated for the RASSF1A gene, whereas 17/39 (44%) EECs and 6/14 (43%) AHs were positive for the methylation of the RARb2 gene. No significant results were obtained for the other genes (P16, MGMT and GSTPi). Interestingly, 4/11 (36%) and 6/11 (55%) histologically normal endometrial tissues adjacent to EEC showed, respectively, RASSF1A and RARb2 gene methylation. Furthermore, these 11 specimens were microsatellite stable and showed similar proliferative, cell cycle and apoptotic mean labelling indices as the normal endometrial control tissues.CONCLUSIONS: Promoter region methylation of RASSF1A and RARb2 genes is an early event in endometrial carcinogenesis.
KW - Aged
KW - Aged, 80 and over
KW - Carcinoma, Endometrioid/genetics
KW - DNA Methylation
KW - Endometrial Neoplasms/genetics
KW - Endometrium/metabolism
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Microsatellite Instability
KW - Middle Aged
KW - Promoter Regions, Genetic/genetics
KW - Receptors, Retinoic Acid/genetics
KW - Tumor Suppressor Proteins/genetics
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U2 - 10.1111/j.1365-2559.2008.03147.x
DO - 10.1111/j.1365-2559.2008.03147.x
M3 - Article
C2 - 18783461
SN - 0309-0167
VL - 53
SP - 525
EP - 532
JO - Histopathology
JF - Histopathology
IS - 5
ER -
