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.
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Acknowledgements
We thank all collaborative researchers involved in this study. We also thank Mr. Motoyoshi Iwakoshi, Ms. Tomoyo Kakita, and the technical staff of the Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Cancer Institute, for their excellent technical support.
Funding
This study was supported by JSPS/MEXT KAKENHI (25460429, 21K06932).
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The study protocol was approved by the ethics committee of Tokyo Metropolitan Geriatric Hospital (No. 260303) and Cancer Institute Hospital (No. 2012-1068). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
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Honma, N., Arai, T., Matsuda, Y. et al. Estrogen concentration and estrogen receptor-β expression in postmenopausal colon cancer considering patient/tumor background. J Cancer Res Clin Oncol 148, 1063–1071 (2022). https://doi.org/10.1007/s00432-021-03889-9
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DOI: https://doi.org/10.1007/s00432-021-03889-9