Aromatase and comparative response to its inhibitors in two types of endometrial cancer.
Aromatase activity (AA) was evaluated totally in 80 tumors collected from primary endometrial cancer (EC) patients. All patients were divided into cases belonging to the types I or II of EC (respectively, 50 and 30 observations). Samples of malignant endometrium from type II demonstrated inclination to the higher AA in comparison with type I samples; the difference reached level of statistical significance in non-smoking patients (p=0.02). Although no positive correlation was revealed between AA in EC tissue and percentage of cells with DNA damage in normal endometrium from the same patients, the rate of DNA damage (percent of comets, comet's tail average length, etc.) was higher in intact endometrium collected from patients with type II of the disease. In 19 tumor samples, CYP19 gene expression was evaluated by RT-PCR and level of mRNA signal demonstrated positive correlation with AA (R(s)=+0.63, p=0.05) in the whole this material. Of note, though, CYP19 mRNA expression was not revealed in six cases, and all of them belonged to the type I of disease. Finally, in 23 EC patients (15 with type I and 8 with type II of the disease) effects of 2 weeks treatment with letrozole (10 pts) and exemestane (13 pts) were evaluated in neoadjuvant setting. Although diminishing of endometrial M-echo signal and the increases in FSH and LH concentration after treatment were more pronounced in type I patients, decrease in tumor PR content (p=0.04) was more revealing in patients with type II of EC; besides, the decreases in AA in tumor tissue by the end of treatment were noted predominantly in patients with lower body weight (BMI <27.5). Thus, although type II of EC is frequently considered as hormone-independent, increased ability of this type of the tumor to estrogen biosynthesis (at CYP19 gene and protein level) may lead to the reconsideration of such conclusion and warrants further investigation. The search of possible ethnic differences in AA and in the biologic response to aromatase inhibitors in EC can be of importance too.
Berstein
L
L
Laboratory of Oncoendocrinology, N.N. Petrov Research Institute of Oncology, St. Petersburg 197758, Russia. levmb@endocrin.spb.ru
Kovalevskij
A
A
Zimarina
T
T
Maximov
S
S
Gershfeld
E
E
Vasilyev
D
D
Baisheva
S
S
Baymakhasheva
A
A
Thijssen
J H H
JH
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001141:Aromatase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D018269:Carcinoma, Endometrioid / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D020552:Comet Assay; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000032:analysis; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D001141:Aromatase