Naoko Honma1,2, Tomio Arai3, Yoko Matsuda4, Yosuke Fukunaga5, Yuri Akishima-Fukasawa6, Noriko Yamamoto7,8, Hiroshi Kawachi7,8, Yuichi Ishikawa7,9, Kengo Takeuchi7,8, Tetuo Mikami6. 1. Department of Pathology, Faculty of Medicine, Toho University, Omori-Nishi 5-21-16, Ota-ku, Tokyo, 143-8540, Japan. naoko.honma@med.toho-u.ac.jp. 2. Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Ariake 3-8-31, Koto-ku, Tokyo, 135-8550, Japan. naoko.honma@med.toho-u.ac.jp. 3. Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Sakaecho 35-2, Itabashi-ku, Tokyo, 173-0015, Japan. 4. Oncology Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Ikenobe 1750-1, Kita-gun, Miki, Kagawa, 761-0793, Japan. 5. Department of Gastroenterological Surgery, Gastroenterological Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake 3-8-31, Koto-ku, Tokyo, 135-8550, Japan. 6. Department of Pathology, Faculty of Medicine, Toho University, Omori-Nishi 5-21-16, Ota-ku, Tokyo, 143-8540, Japan. 7. Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Ariake 3-8-31, Koto-ku, Tokyo, 135-8550, Japan. 8. Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake 3-8-31, Koto-ku, Tokyo, 135-8550, Japan. 9. Department of Pathology, International University of Health and Welfare, Mita 1-4-3, Minato-ku, Tokyo, 108-8329, Japan.
Abstract
PURPOSE: A large number of studies have suggested an inhibitory role of estrogens against colorectal cancer (CRC), but persistent controversy exists. CRC characteristics are affected by sex, age, and tumor locus, suggesting the need for a systematic study considering these factors. The purpose of this study was to verify the difference in the pathobiological role of estrogens in CRC according to patient/tumor backgrounds. METHODS: Surgical specimens from 116 postmenopausal women (≥ 70 years/o, n = 74; < 70 years/o, n = 42) were studied. Estrogen receptor-β (ER-β), the main ER in the colorectal epithelium, was immunohistochemically examined. The concentrations of estradiol (E2) and estrone (E1) were examined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). These factors were compared according to the tissue type (cancerous or non-cancerous), patients' age, tumor backgrounds (locus, histology, pathological stage, status of mismatch repair protein = MMR), and clinical outcome. RESULTS: ER-β-positivity, higher E2 concentration, deficient-MMR, and medullary/mucinous histology (Med/Muc) were closely related to right-sided tumors in women who were aged ≥ 70 years /o (R-Ca ≥ 70) and also closely related to each other. ER-β reduction compared with non-cancerous counterparts was observed only in left-sided tumors of patients < 70 years /o (L-Ca < 70), non-Med/Muc, or proficient-MMR tumors. CONCLUSION: The present results suggest that estrogens do not suppress, but rather promote, R-Ca ≥ 70, Med/Muc, or deficient-MMR tumors, whereas estrogens suppress L-Ca < 70, non-Med/Muc, or proficient-MMR tumors, confirming the difference in pathobiological role of estrogens in postmenopausal colon cancer according to the patients' age and tumor background. This may at least partly explain the controversy regarding the association between estrogens and CRC.
PURPOSE: A large number of studies have suggested an inhibitory role of estrogens against colorectal cancer (CRC), but persistent controversy exists. CRC characteristics are affected by sex, age, and tumor locus, suggesting the need for a systematic study considering these factors. The purpose of this study was to verify the difference in the pathobiological role of estrogens in CRC according to patient/tumor backgrounds. METHODS: Surgical specimens from 116 postmenopausal women (≥ 70 years/o, n = 74; < 70 years/o, n = 42) were studied. Estrogen receptor-β (ER-β), the main ER in the colorectal epithelium, was immunohistochemically examined. The concentrations of estradiol (E2) and estrone (E1) were examined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). These factors were compared according to the tissue type (cancerous or non-cancerous), patients' age, tumor backgrounds (locus, histology, pathological stage, status of mismatch repair protein = MMR), and clinical outcome. RESULTS: ER-β-positivity, higher E2 concentration, deficient-MMR, and medullary/mucinous histology (Med/Muc) were closely related to right-sided tumors in women who were aged ≥ 70 years /o (R-Ca ≥ 70) and also closely related to each other. ER-β reduction compared with non-cancerous counterparts was observed only in left-sided tumors of patients < 70 years /o (L-Ca < 70), non-Med/Muc, or proficient-MMR tumors. CONCLUSION: The present results suggest that estrogens do not suppress, but rather promote, R-Ca ≥ 70, Med/Muc, or deficient-MMR tumors, whereas estrogens suppress L-Ca < 70, non-Med/Muc, or proficient-MMR tumors, confirming the difference in pathobiological role of estrogens in postmenopausal colon cancer according to the patients' age and tumor background. This may at least partly explain the controversy regarding the association between estrogens and CRC.
Authors: Karin Dahlman-Wright; Vincent Cavailles; Suzanne A Fuqua; V Craig Jordan; John A Katzenellenbogen; Kenneth S Korach; Adriana Maggi; Masami Muramatsu; Malcolm G Parker; Jan-Ake Gustafsson Journal: Pharmacol Rev Date: 2006-12 Impact factor: 25.468
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