目的 探讨表皮生长因子受体(epidermal growth factor receptor, EGFR)与B淋巴细胞瘤-2基因(B-cell lymphoma-2, Bcl-2)在乳腺癌中的表达状况及其临床意义。方法 采用免疫组化(二步法)实验方法检测539例乳腺癌组织雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR)、人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)以及EGFR、Bcl-2的表达。结果 EGFR的表达以三阴性乳腺癌最高 (44.4%);Bcl-2的表达以管腔型乳腺癌最高(71.7%)。在EGFR的表达上,三阴性乳腺癌与管腔型乳腺癌(χ2=9.02, P<0.05)、HER-2受体阳性组乳腺癌患者(χ2=5.78, P<0.05)相比表达率更高;在Bcl-2表达上,管腔型乳腺癌与HER-2受体阳性组乳腺癌(χ2=70.73, P<0.0001)、三阴性乳腺癌(χ2=71.76, P<0.0001)的患者相比表达率更高。两者的表达与其他病理特征的差异均无统计学意义。乳腺癌组织学分级越高EGFR的阳性表达率越高(χ2=11.38,P<0.05),而Bcl-2的阳性表达率越低(χ2=6.92, P<0.05)。PR、Bcl-2与ER表达呈正相关,相关系数分别为0.712、0.599,差异有统计学意义(P<0.01)。同时,PR与Bcl-2间也呈正相关关系(r=0.599,P<0.01)。而ER、PR分别与HER-2、EGFR之间以及HER-2与Bcl-2之间都呈负相关,它们的相关系数依次为-0.366、-0.133、-0.453、-0.195和-0.392。结论 EGFR与Bcl-2的表达在乳腺癌不同分子亚型间存在差异; EGFR以及Bcl-2的表达可以作为乳腺癌发生、发展的评价指标,有助于评估乳腺癌的生物学行为并指导临床治疗以及制定预后策略。
Abstract
Objective To study the expression of epidermal growth factor receptor (EGFR) and B-cell lymphoma-2 (Bcl-2) in breast cancer subtype and their relationship with clinicopathological features and the expression of ER,PR and HER-2. Methods Immunohistochemistry was performed to detect the expression of EGFR and Bcl-2 in 539 patients with breast cancer and its correlation with clinicopathological parameters was analyzed. Results The expression rate of EGFR in three negative breast cancer group (χ2=9.78,P=0.008) and Bcl-2 in luminal breast cancer group (χ2=114.11, P<0.0001) were 44.4% and 71.7%, which were the highest in all groups. The expression of EGFR showed a statistically significant difference in histological grade (χ2=11.38,P=0.003), and the expression of Bcl-2 showed a statistically significant difference in histological grade (χ2=6.92, P=0.041) and pathological type (χ2=5.39,P=0.022). No significant difference was found between the expression of both and other clinicopathological features. The expression of PR and Bcl-2 was positively correlated with the expression of Bcl-2, and their correlation coefficients were 0.712(P<0.01) and 0.599(P<0.01), respectively, which was the same with the expression between PR and Bcl-2 (r=0.599,P<0.01). However, there was a negative correlation between ER,PR and HER-2, Bcl-2 respectively, and their correlation coefficient were -0.366,-0.133,-0.453,-0.392 successively. In addition, no correlation was found between EGFR and HER-2, Bcl-2 (P>0.05). Conclusions The expression of EGFR and Bcl-2 is different in breast cancer subtypes. Joint detection of the expression of EGFR and Bcl-2 could be used as index of breast cancer occurrence, development, and help to guide clinical treatment and prognosis of strategy.
关键词
EGFR /
Bcl-2 /
乳腺癌 /
临床病理特征
Key words
EGFR /
Bcl-2 /
breast cancer /
clinicopathological features
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参考文献
[1] Balslev I, Axelsson C K, Zedeler K, et al. The Nottingham Prognostic Index applied to 9,149 patients from the studies of the Danish Breast Cancer Cooperative Group (DBCG) [J]. Breast Cancer Res Treat, 1994, 32(3):281-290.
[2] Burness M L, Grushko T A, Olopade O I.Epidermal growth factor receptor in triple-negative and basal-like breast cancer: promising clinical target or only a marker[J]. Cancer J, 2010, 16(1):23-32.
[3] Park S, Koo J S, Kim M S,et al. Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry [J]. Breast, 2012, 21(1):50-57.
[4] Gehrig P A, Van L L, Olatidoye B. Estrogen receptor status, determined by immunohistochemistry, as a predictor of the recurrence of stage I endometrial carcinoma [J]. Cancer, 1999, 86(10):2083-2089.
[5] 《乳腺癌HER2检测指南》编写组.乳腺癌HER2检测指南(2009版)[J]. 中华病理学杂志, 2009, 38(12):836-840.
[6] 许良中,杨文涛. 免疫组织化学结果的判定标准 [J]. 中华癌症学杂志, 2006, 38(6): 1-3.
[7] Cheang, M C, Chia S K, Voduc D,et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer [J]. J Natl Cancer Inst, 2009, 101(10):736-750.
[8] 李彦国,王 欢,张秉明,等. 农村妇女乳腺癌危险因素的病例对照研究[J].中国医刊,2013,48(7):75-77.
[9] 盛唯瑾,高瑞娟,甄永苏. EGFR单链抗体-力达霉素融合蛋白抑制人乳腺癌MCF-7细胞增殖与侵袭的研究[J]. 医学研究杂志,2014,43(6):25-30.
[10] 李珊珊. EGFR在乳腺癌中的表达及意义[J].山东医药,2012,52(20):89-90.
[11] Nicholson R I. EGFR and cancer prognosis [J]. Eur J Cancer, 2001, 37 (4):9-15.
[12] Nielsen T O, Hsu F D, Jensen K,et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma [J]. Clin Cancer Research, 2004, 10(16):5367-5374.
[13] Kim M J, Ro J Y, Ahn S H,et al. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes [J]. Human pathology, 2006, 37(9):1217-1226.[14] Zaha D C, Lazar E, Lazureanu C, et al. Clinicopathologic features and five years survival analysis in molecular subtypes of breast cancer [J]. Rom J Morphol Embryol, 2010, 51(1):85-89.
[15] Hellemans P, van Dam P A, Weyler J,et al. Prognostic value of bcl-2 expression in invasive breast cancer [J]. Br J Cancer, 1995, 72(2):354-360.
[16] 徐兵河.复发转移乳腺癌的化学治疗[J].中国实用内科杂志,2007,24(4):1913-1916.
[17] 涂小煌. 乳腺癌的化疗方案[J].中国临床医师,2011,39(7):9-11.
[18] Gee J M, Ellis I O, Robertson J F,et al. Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy [J]. Int J Cancer, 1994, 59(5):619-628.
[19] Rolland P, Spendlove I, Madjd Z,et al. The p53 positive Bcl-2 negative phenotype is an independent marker of prognosis in breast cancer [J]. Int J Cancer, 2007, 120(6):1311-1317.
[20] dos Santos LG, Lopes-Costa P V, dos Santos A R,et al. Bcl-2 oncogene expression in estrogen receptor-positive and negative breast carcinoma [J]. Eur J Gynaecol Oncol, 2008, 29(5):459-461.
[21] 李 忻,张 韫,杨 鑫,等. 浸润性乳腺癌组织中人表皮生长因子受体2表达的检测方法比较[J].中日友好医院学报,2012,26(6):326-328.
[22] McCawley L J, O’Brien P, Hudson L G. Overexpression of the epidermal growth factor receptor contributes to enhanced ligand-mediated motility in keratinocyte cell lines[J]. Endocrinology. 1997, 138(1):121-127.
[23] Sibilia M, Fleischmann A, Behrens A,et al. The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development [J]. Cell,2000,102(2):211-220.
[24] 谢文秀,杨俊兰,焦顺昌,等.乳腺癌分子分型与腋窝淋巴结转移相关性分析[J]. 军医进修学院学报, 2011, 32(7): 32-33.
基金
国家科技支撑计划项目(SQ2015BA1300692);北京自然科学基金(7132027)