Comparison of macroscopic appearance and estrogen receptor-alpha regulators after gene alteration in human endometrial cancer.
The existence of two types of endometrial cancer (hyperplasia-associated type [type I] and atrophy-associated type [type II]) is well established. To test if different molecular genetic pathways are involved in the pathogenesis of type I and II disease, we examined pathologic features and the genetic alterations of K-Ras, MDM2 and p53 (which are considered to be involved in regulation of the estrogen receptor-alpha) in human endometrial tissue samples using several modified PCR methods. We found a significant difference in histologic grade (P < 0.001), degree of invasion (P < 0.001), stage grouping (P < 0.001) and estrogen receptor status (P < 0.01) between type I and II cases. There was a tendency for cases with K-Ras point mutations to be of type I, and for cases with the p53 point mutation to be of type II; however, we found that these mutations or alternative splicing of MDM2 was rarely involved and there was no significant difference in frequency of these alterations between types I and II. There must therefore be another structural or functional difference of Ras, MDM2 or p53 between type I and type II cancer. These unknown factors may be responsible for the difference between estrogen-dependent and estrogen-independent growth in human endometrial cancer.
Departments of Pathology and Obstetrics and Gynecology, Ibaraki Prefectural Central Hospital and Cancer Center, Ibaraki, Japan; and Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
M.
M
Hori
K.
K
Takechi
Y.
Y
Arai
H.
H
Yomo
M.
M
Itabashi
J.
J
Shimazaki
S.
S
Inagawa
M.
M
Hori