Aromatase Expression in Stromal Cells of Endometrioid Endometrial Cancer Correlates with Poor Survival

• Published in: Clinical cancer research Vol. 11; no. 6; pp. 2188 - 2194
• Main Authors: SEGAWA, Tomoya, SHOZU, Makio, MURAKAMI, Kouich, KASAI, Tadayuki, SHINOHARA, Kazunori, NOMURA, Kazuhito, OHNO, Satoshi, INOUE, Masaki
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.03.2005
• Subjects: Antineoplastic agents; Aromatase - genetics; Aromatase - metabolism; Biological and medical sciences; Carcinoma, Endometrioid - diagnosis; Carcinoma, Endometrioid - enzymology; Disease Progression; Endometrium - enzymology; Epithelial Cells - enzymology; Epithelial Cells - pathology; Estrogen formation; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; hybridization; immunohistochemistry; in situ; In Situ Hybridization; Lymphatic Metastasis - pathology; Medical sciences; Middle Aged; Myometrium - enzymology; Myometrium - pathology; Neoplasm Invasiveness - pathology; Pharmacology. Drug treatments; Prognosis; prognostic indicators; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stromal Cells - enzymology; survival analysis; Survival Rate; Tumors; Endometrium cancer; Enzyme; Uterine diseases; Stromal cell; Estrogen synthase; Malignant tumor; Gene expression; Survival; Female genital diseases
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-1859

Purpose and Experimental Design: To assess the prognostic significance of intratumoral aromatase in endometrioid endometrial cancer, sections from 55 patients with endometrial cancer were evaluated for expression of aromatase using immunohistochemistry, and the correlation between aromatase expression and clinicopathologic parameters were analyzed. Results: Immunohistochemical staining for aromatase was positive for 32 (58%), 20 (36%), and 19 (34%) patients in cancer epithelial cells, stromal cells, and myometrial cells around the flank invasion, respectively. In situ hybridization also detected aromatase mRNA in all three types of cells. RT-PCR analysis revealed that aromatase mRNA was 2.5 ± 1.0 amol/μg total RNA (mean ± SE; n = 7) in tumor tissue. Western blot analysis detected the expected aromatase protein size of 58 kDa in cancer tissues more abundantly than in cancer-free endometrium ( n = 3). The immunoreactivity in stromal cells correlated positively with advanced surgical stage and poor survival. Survival analysis revealed that the immunoreactivity of stromal cells was a significant prognostic factor, independent of histologic grade, muscular invasion, and lymph node metastasis, but dependent on surgical stage. By contrast, the immunoreactivity of aromatase both in cancer epithelial cells and myometrial cells did not correlate with prognosis. Conclusions: To the best of our knowledge, this is the first evidence associating intratumoral aromatase expression in stromal cells and poor survival in endometrioid endometrial cancer. This positive linkage indicates that local expression of aromatase plays a role in tumor progression through the formation of in situ estrogens. In situ expression of aromatase may offer a potential target for management of endometrial cancers.