에스트로겐 수용체 β 발현과 유방암 재발과의 관련성
The Relationship Between the Expression of Estrogen Receptor β and Recurrence in Breast Cancer
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Background It has been reported that estrogen receptor beta (ERβ) mRNA expression was down-regulated during carcinogenesis and was inversely related to estrogen receptor alpha (ERα) expression in breast cancer. The association of ERβ mRNA expression to tamoxifen resistance has also been reported. In this study, the expression of ERα and ERβ via immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) was prompted, and an attempt was made to find out the relationship between ERβ expression and recurrence in the hormonal therapy group, and between ERβ expression and known prognostic factors. Methods Tumor specimens were obtained at surgery from 67 female breast cancer patients during the period of September 1995 to December 2000. All the specimens were frozen in liquid nitrogen and kept at -70℃ until they were used. The medical records were analyzed retrospectively. The expressions of ER were analyzed using IHC and RT-PCR methods. Results The median follow-up was at 93.0 months (range: 14-157 months). The percentage of ERα+/ERβ+, ERα+/ERβ-, ERα-/ERβ+, and ERα-/ERβ group were 35.9% 9.4%, 47.2%, and 7.5%, respectively, in 53 patients with hormonal therapy. ERβ was positive in 42 (82.3%) of 51 ER-positive patients. In the hormonal therapy group, the recurrence rates of each group was 15.8%, 0%, 40.0%, and 0%, respectively. In this group, the ERβ expression tended to recur, but there was no clinical significance (p=0.084). Conclusion The ERβ expression may be a predictive marker of a poor response to endocrine therapy in breast cancer patients, although this needs to be confirmed in additional studies.
Abstract
Background It has been reported that estrogen receptor beta (ERβ) mRNA expression was down-regulated during carcinogenesis and was inversely related to estrogen receptor alpha (ERα) expression in breast cancer. The association of ERβ mRNA expression to tamoxifen resistance has also been reported. In this study, the expression of ERα and ERβ via immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) was prompted, and an attempt was made to find out the relationship between ERβ expression and recurrence in the hormonal therapy group, and between ERβ expression and known prognostic factors. Methods Tumor specimens were obtained at surgery from 67 female breast cancer patients during the period of September 1995 to December 2000. All the specimens were frozen in liquid nitrogen and kept at -70℃ until they were used. The medical records were analyzed retrospectively. The expressions of ER were analyzed using IHC and RT-PCR methods. Results The median follow-up was at 93.0 months (range: 14-157 months). The percentage of ERα+/ERβ+, ERα+/ERβ-, ERα-/ERβ+, and ERα-/ERβ group were 35.9% 9.4%, 47.2%, and 7.5%, respectively, in 53 patients with hormonal therapy. ERβ was positive in 42 (82.3%) of 51 ER-positive patients. In the hormonal therapy group, the recurrence rates of each group was 15.8%, 0%, 40.0%, and 0%, respectively. In this group, the ERβ expression tended to recur, but there was no clinical significance (p=0.084). Conclusion The ERβ expression may be a predictive marker of a poor response to endocrine therapy in breast cancer patients, although this needs to be confirmed in additional studies.
참고문헌 (33)
- Green S, "Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A", Nature, 320, pp.134~139 (1986)
- Greene GL, "Sequence and expression of human estrogen receptor complementary DNA", Science, 231, pp.1150~1154 (1986)
- Osborne CK, "Tamoxifen in the treatment of breast cancer", N Engl J Med, 339, pp.1609~1618 (1998)
- Clarke R, "Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling", Oncogene, 22, pp.7316~7339 (2003)
- Kuiper GG, "Cloning of a novel receptor expressed in rat prostate and ovary", Proc Natl Acad Sci U S A, 93, pp.5925~5930 (1996)
- Hu YF, "Increased expression of estrogen receptor beta in chemically transformed human breast epithelial cells", Int J Oncol, 12, pp.1225~1228 (1998)
- Speirs V, "Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer?", Cancer Res, 59, pp.525~528 (1999)
- Jarvinen TA, "Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer", Am J Pathol, 156, pp.29~35 (2000)
- Mann S, "Estrogen receptor beta expression in invasive breast cancer", Hum Pathol, 32, pp.113~118 (2001)
- Omoto Y, "Clinical value of the wild-type estrogen receptor beta expression in breast cancer", Cancer Lett, 163, pp.207~212 (2001)
- Shaaban AM, "Declining estrogen receptor-beta expression defines malignant progression of human breast neoplasia", Am J Surg Pathol, 27, pp.1502~1512 (2003)
- Nakopoulou L, "The favourable prognostic value of oestrogen receptor beta immunohistochemical expression in breast cancer", J Clin Pathol, 57, pp.523~528 (2004)
- Choi Y, "Estrogen receptor beta in breast cancer: associations between ERbeta, hormonal receptors, and other prognostic biomarkers", Appl Immunohistochem Mol Morphol, 13, pp.19~24 (2005)
- Skliris GP, "Expression of oestrogen receptor-beta in oestrogen receptor-alpha negative human breast tumours", Br J Cancer, 95, pp.616~626 (2006)
- Hopp TA, "Low levels of estrogen receptor beta protein predict resistance to tamoxifen therapy in breast cancer", Clin Cancer Res, 10, pp.7490~7499 (2004)
- Myers E, "Inverse relationship between ER-beta and SRC-1 predicts outcome in endocrine-resistant breast cancer", Br J Cancer, 91, pp.1687~1693 (2004)
- Borgquist S, "Oestrogen receptors alpha and beta show different associations to clinicopathological parameters and their co-expression might predict a better response to endocrine treatment in breast cancer", J Clin Pathol, 61, pp.197~203 (2008)
- Cappelletti V, "Prospective evaluation of estrogen receptor-beta in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients", Endocr Relat Cancer, 11, pp.761~770 (2004)
- Chang HG, "Tamoxifen-resistant breast cancers show less frequent methylation of the estrogen receptor beta but not the estrogen receptor alpha gene", J Mol Med (Berl), 83, pp.132~139 (2005)
- Murphy LC, "Relationship of coregulator and oestrogen receptor isoform expression to de novo tamoxifen resistance in human breast cancer", Br J Cancer, 87, pp.1411~1416 (2002)
- Speirs V, "Distinct expression patterns of ER alpha and ER beta in normal human mammary gland", J Clin Pathol, 55, pp.371~374 (2002)
- Gruvberger-Saal SK, "Estrogen receptor beta expression is associated with tamoxifen response in ERalpha-negative breast carcinoma", Clin Cancer Res, 13, pp.1987~1994 (2007)
- 박민호, "에스트로겐 수용체 알파 음성 및 프로게스테론 수용체양성인유방암환자에서에스트로겐수용체 베타의 발현이 호르몬 치료에 미치는 영향", Journal of Breast Cancer, 12(3), pp.156~162 (2009), 한국유방암학회
- Baek JM, "Expression of estrogen receptor beta, estrogen receptor alpha and cyclooxygenase Ⅱ in advanced breast cancer", J Breast Cancer, 8, pp.45~51 (2005)
- Kim SI, "Comparison of estrogen receptor beta expression between breast cancer and normal mammary tissue and relationship with clinicopathological factors", J Breast Cancer, 8, pp.99~104 (2005)
- Association of Directors of Anatomic and Surgical Pathology, "Recommendations for the reporting of breast carcinoma", Hum Pathol, 27, pp.220~224 (1996)
- Greene FL, "AJCC cancer staging manual" (2002), Springer- Verlag
- Lee JS, "Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression", Gynecol Oncol, 85, pp.469~475 (2002)
- Chomczynski P, "Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction", Anal Biochem, 162, pp.156~159 (1987)
- Roger P, "Rochefort H. Decreased expression of estrogen receptor beta protein in proliferative preinvasive mammary tumors", Cancer Res, 61, pp.2537~2541 (2001)
- Balfe P, "Estrogen receptor alpha and beta profiling in human breast cancer", Eur J Surg Oncol, 30, pp.469~474 (2004)
- Early Breast Cancer Trialists' Collaborative Group, "Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women", Lancet, 339, pp.1~15 (1992)
- Early Breast Cancer Trialists' Collaborative Group, "Tamoxifen for early breast cancer: an overview of the randomised trials", Lancet, 351, pp.1451~1467 (1998)
