乳腺癌原发灶和同侧腋窝淋巴结转移灶中激素受体及Her-2表达差异及其对预后的影响

doi:10.13481/j.1671-587x.20190228

摘要/Abstract

摘要： 目的：研究雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（Her-2）在乳腺癌原发灶及同侧腋窝淋巴结转移灶中的表达差异，探讨这种差异对患者预后的影响。方法：收集120例乳腺浸润性导管癌伴有同侧腋窝淋巴结转移女性患者的临床资料和病理标本，采用免疫组织化学法检测乳腺癌患者原发灶和同侧腋窝淋巴结转移灶中ER、PR、Her-2和Ki-67的表达。采用配对χ²检验分析原发灶和转移灶受体表达的差异，采用χ²检验分析Ki-67表达与受体表达关联性以及乳腺癌一般临床特征与受体表达的关联性，采用Spearman相关分析法分析临床分期与受体表达差异的相关性，采用Kaplan-Meier法进行生存分析。结果：ER、PR和Her-2在乳腺癌患者原发灶和同侧淋巴结转移灶中表达水平存在一定差异，但差异均无统计学意义（P>0.05）。乳腺癌临床分期与ER和PR表达差异有关联（P<0.05）。乳腺癌患者原发灶中Ki-67表达与原发灶中ER和PR表达有关联（P<0.05）。ER在原发灶和同侧腋窝淋巴结转移灶表达不一致的患者与ER表达一致患者的总生存率（OS）和无病生存率（DFS）比较差异有统计学意义（P<0.05），ER表达不一致患者5年OS和DFS较低。原发灶ER阳性且淋巴结转移灶ER阳性患者（+/+） OS和DFS高于原发灶ER阳性但淋巴结转移灶ER阴性患者（+/-）（P<0.05）。原发灶ER阴性且淋巴结转移灶ER阴性患者（-/-） OS高于原发灶ER阴性但淋巴结转移灶ER阳性的患者（-/+）（P<0.05），但DFS比较差异无统计学意义（P=0.119）。结论：乳腺癌患者原发灶和腋窝淋巴结转移灶中ER、PR和Her-2存在差异表达，且可反映患者的预后，对于原发灶和腋窝淋巴结转移灶受体表达不一致患者需要进行更加个体化的诊治。

关键词: 乳腺肿瘤, 腋窝淋巴结, 雌激素受体, 孕激素受体, 人表皮生长因子受体2

Abstract: Objective: To investigate the discordance for estrogen receptor (ER), progestin receptor (PR) and human epidermal growth factor receptor 2 (Her-2) expressions in the primary lesion of breast cancer and ipsilateral axillary lymph node metastases, and to discuss the effect of discordance on the prognosis of patients.Methods: The climical materials and pathological samples of 120 cases of breast cancer patients with ipsilateral axillary lymph node metastasis were collected.The expressions of ER, PR, Her-2 and Ki-67 in the primary lesion and axillary lymph node metastasis of the breast cancer patients were detected by immunohistochemistry.Paired Chi-square test was used to analyze the differences in the receptor expressions between the primary lesion and the axillary lymph node metastasis.Chi-square test was used to evaluate the correlations between the Ki-67 expression and the receptor expressions and the correlations between the clinical characteristics of breast cancer and the expression differences in ER, PR and Her-2.Spearman correlation analysis was used to analyze the correlations between the clinical stages of breast cancer and the expression differences of ER, PR and Her-2.Survival analysis was conducted by Kaplan-Meier method.Results: There were some differences in the expression of levels of ER, PR and Her-2 between the primary lesion and the ipsilateral lymph node metastasis, but there was no statistically significant differences (P>0.05).The clinical stages of breast cancer were related to the expression differences of ER and PR (P<0.05).The Ki-67 expression was significantly associated with the expressions of ER and PR in primary lesion of breast cancer patients(P＜0.05).There were a statistically significant differences in the overall survival (OS) and disease-free survival (DFS) between concordant and discordant cases for ER status in the primary lesion and the corresponding lymph node metastasis (P<0.05).The OS and DFS were significantly lower in the discordant cases for ER status.The OS and DFS of the patients with ER-positive in the primary lesion and ER-positive in the lymph node metastasis were higher than those of the patients with ER positive in the primary lesion and ER negative in the lympy node metastasis (+/+ vs.+/-)(P< 0.05).The OS of the patients with ER-negative in the primary lesion and ER-negative in the lymph node metastasis than that of the patients with ER-negative in the primary lesion and ER-positive in the lymph node metastasis(-/+ vs. -/+)(P< 0.05);but the difference of DFS was not statistically significant (P=0.119).Conclusion: The expressions of ER,PR and Her-2 were discordant between primary lesion and lymph node in the breast cancer patients, and the discordance may reflect the prognosis of these patients.The patients with discordant expressions of ER,PR and Her-2 in the primary lesion and the lymph node metastasis need more individualized diagnosis and treatment.

Key words: breast neoplasms, axillary lymph node, estrogen receptor, progestin receptor, human epidermal growth factor receptor-2

中图分类号:

R737. 9

周红旭, 杜烨, 于云鹤, 韩冰, 李嗣杰, 郭国强, 范志民. 乳腺癌原发灶和同侧腋窝淋巴结转移灶中激素受体及Her-2表达差异及其对预后的影响[J]. 吉林大学学报(医学版), 2019, 45(02): 376-382.

ZHOU Hongxu, DU Ye, YU Yunhe, HAN Bing, LI Sijie, GUO Guoqiang, FAN Zhimin. Discordance for hormone receptors and Her-2 expressions in primary lesion and ipsilateral axillary lymph node metastasis of breast cancer and its influence in prognosis[J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 376-382.

参考文献

[1] TORRE L A, SIEGEL R L, WARD E M,et al.Global cancer incidence and mortality rates and trends:An update[J].Cancer Epidemiol Biomarkers Prev, 2016,25(1):16-27.
[2] FALCK A K, FERNÖ M, BENDAHL P O,et al.Does analysis of biomarkers in tumor cells in lymph node metastases give additional prognostic information in primary breast cancer?[J].World J Surg, 2010, 34(7):1434-1441.
[3] AITKEN S J, THOMAS J S, LANGDON S P,et al.Quantitative analysis of changes in er, pr and her2 expression in primary breast cancer and paired nodal metastases[J].Ann Oncol, 2010, 21(6):1254-1261.
[4] KÜMLER I, BALSLEV E, KNOP AS,et al.Expression patterns of biomarkers in primary tumors and corresponding metastases in breast cancer[J].Appl Immunohistochem Mol Morphol, 2018, 26(1):13-19.
[5] GEORGESCU R, BOROS M, MONCEA D,et al.Discordance rate in estrogen receptor, progesterone receptor, her2 status, and ki67 index between primary unifocal and multiple homogenous breast carcinomas and synchronous axillary lymph node metastases have an impact on therapeutic decision[J].Appl Immunohistom Mol Morphol, 2018, 26(8):533-538.
[6] 徐雨杰, 王梦申, 王翀,等.Luminal A型乳腺癌原发灶与淋巴结转移灶表型标志物差异性研究[J].中华肿瘤防治杂志, 2018, 25(9):642-646.
[7] 金梁斌, 姚自翔, 孔令泉,等.同期腋窝转移淋巴结受体检测在激素受体阴性乳腺癌中的临床意义[J].中国肿瘤临床, 2013, 40(15):911-913.
[8] 刘琪, 左文述, 王新昭,等.乳腺癌原发灶和淋巴结转移灶激素受体及HER-2与Ki-67表达相关性分析[J].中华肿瘤防治杂志, 2013, 20(15):1153-1157.
[9] 田枫, 张建国, 仲雷.乳腺浸润性导管癌病灶与腋窝转移淋巴结中ER和Her-2表达的关系[J].中国普通外科杂志, 2012, 21(11):1405-1409.
[10] 房兆国, 范小超, 杨奔,等.乳腺癌原发灶与转移灶分子分型指标表达差异的研究[J].中华肿瘤防治杂志, 2017, 24(16):1175-1178.
[11] DIECI M V, BARBIERI E, PIACENTINI F,et al.Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact:A single-institution analysis[J].Ann Oncol, 2013, 24(1):101-108.
[12] FALCK A K, BENDAHL P O, CHEBIL G,et al.Biomarker expression and st gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years' follow-up[J].Breast Cancer Res Treat, 2013, 140(1):93-104.
[13] 杨文涛, 步宏.乳腺癌雌、孕激素受体免疫组织化学检测指南[J].中华病理学杂志, 2015,44(4):237-239.
[14] 《乳腺癌HER2检测指南》编写组.乳腺癌HER2检测指南(2014版)[J].中华病理学杂志, 2014, 43(4):262-267.
[15] COATES A S, WINER E P, GOLDHIRSCH A,et al.Tailoring therapies——improving the management of early breast cancer:St gallen international expert consensus on the primary therapy of early breast cancer 2015[J].Ann Oncol, 2015, 26(8):1533-1546.
[16] FASCHING P A, HEUSINGER K, HAEBERLE L,et al.Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment[J].BMC Cancer, 2011, 11:486.
[17] URRUTICOECHEA A, SMITH I E, DOWSETT M.Proliferation marker ki-67 in early breast cancer[J].J Clin Oncol, 2005, 23(28):7212-7220.
[18] BOTTINI A, BERRUTI A, BERSIGA A,et al.Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer[J].Br J Cancer, 2001, 85(8):1106-1112.
[19] KLEIN C A.Parallel progression of primary tumours and metastases[J].Nat Rev Cancer, 2009, 9(4):302-312.
[20] LIU S L, CONG Y, WANG D,et al.Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts[J].Stem Cell Reports, 2014, 2(1):78-91.
[21] NAROD S A, SOPIK V.Is invasion a necessary step for metastases in breast cancer?[J].Breast Cancer Res Treat, 2018, 169(1):9-23.
[22] OSKARSSON T, BATLLE E, MASSAGUÉ J.Metastatic stem cells:Sources, niches, and vital pathways[J].Cell Stem Cell, 2014, 14(3):306-321.
[23] MARUSYK A, TABASSUM D P, ALTROCK P M,et al.Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity[J].Nature, 2014, 514(7520):54-58.