Endometrial glandular dysplasia with frequent p53 gene mutation: a genetic evidence supporting its precancer nature for endometrial serous carcinoma.
OBJECTIVE
Endometrial glandular dysplasia (EmGD) has been recently proposed to be a putative precursor to endometrial serous carcinoma (ESC). The purpose of this study is to determine if EmGD is genetically linked to ESC and if it can be used for early detection.


METHODS
The tumor suppressor p53 gene was sequenced from serial samples of benign and neoplastic endometria with serous differentiation. The study group contained 15 neoplastic uteri and the control group had 12 age-matched benign uteri. A total of 139 informative samples were obtained, including 55 resting endometrium, 37 EmGD, 25 serous endometrial intraepithelial carcinoma (EIC), and 22 ESC. At least one representative section from each uterus was used for p53 immunohistochemical staining to correlate p53 overexpression with gene mutation status.


RESULTS
The mutations of p53 were detected in 0%, 43%, 72%, and 96% in resting endometrium, EmGD, serous EIC, and ESC, respectively. More than 50% of the neoplastic uteri showed at least one identical p53 gene mutant among lesions of EmGD, serous EIC, and/or ESC. The majority of lesions showed overexpression of p53 protein, which was significantly correlated with p53 gene mutation (P < 0.01).


CONCLUSIONS
This genetic evidence strongly supports that EmGD represents the precancer of ESC or serous EIC. Mutation of p53 gene is probably one of the most important factors to initiate the endometrial serous carcinogenesis. Correct identification of EmGD will provide us an opportunity of early diagnosis and a potentially effective therapeutic modality to control ESC.
Jia
Lin
L
Department of Pathology, Arizona Cancer Center, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Liu
Yongjuan
Y
Yi
Xiaofang
X
Miron
Alexander
A
Crum
Christopher P
CP
Kong
Beihua
B
Zheng
Wenxin
W
D000368:Aged; D001483:Base Sequence; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000473:pathology*; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53