Sensitivity analysis on the novel marker GATA3 expression in different surrogate molecular subtypes of breast carcinoma
-
摘要:
目的 比较GATA3结合蛋白（GATA3）、特异性囊肿病液体蛋白15（GCDFP15）和乳腺珠蛋白（MGB）在原发和配对淋巴结转移性乳腺癌替代分子分型的敏感性，探讨GATA3在病理诊断的应用价值。 方法 选取2013年3月~2016年3月在梅州市人民医院病理科确诊的原发和配对淋巴结转移性乳腺癌患者64人，运用免疫组织化学方法和荧光原位杂交技术替代多基因分子检测，把乳腺癌分为：激素受体阳性、HER2阴性（A型）；激素受体阳性、HER2阳性（B型）；激素受体阴性、HER2阳性（C型）；三阴（D型），每型各16例。使用组织芯片免疫组织化学方法检测GATA3、GCDFP15和MGB在原发和配对淋巴结转移性乳腺癌替代分子分型的敏感性，利用H-score评分（0~300）：计算染色程度（0~3+）和染色范围（0%~100%），设定H-score评分得分界值≥50作为阳性结果评定3种抗体在替代分子分型的敏感性。 结果 GATA3在A型和B型原发和配对淋巴结转移性乳腺癌的敏感性明显优于其它两种抗体，差异有统计学意义（P<0.05）；而GATA3在C型和D型的敏感性与其它两种抗体相比未显其优越性，差异无统计学意义（P>0.05）。GATA3在乳腺癌替代分子分型的表达程度不同：在A型和B型显示高表达；在C型和D型显示中、低表达；而GCDFP15和MGB在替代分子分型中表达程度无差异。GATA3在原发和配对淋巴结转移性乳腺癌表达显示很好的一致性，Kappa值为0.826>0.75，而GCDFP15的Kappa值为0.492<0.75，MGB的Kappa值为0.593<0.75，显示一般的一致性。 结论 GATA3在原发和配对淋巴结转移性乳腺癌表达有很好的一致性，GATA3在乳腺癌替代分子分型中敏感性有差异：GATA3在A型和B型显示高表达和高敏感，GATA3在C型显示中度表达和敏感，在三阴癌显示低表达和低敏感性。应重新评估GATA3在激素受体阴性乳腺癌尤其是三阴癌中的诊断价值。 -
关键词:
- GATA3结合蛋白 /
- 乳腺癌替代分子分型 /
- 免疫组织化学 /
- 特异性囊肿病液体蛋白15 /
- 乳腺珠蛋白
Abstract:Objective To compare the sensitivity on GATA3 and GCDFP15 and MGB in different surrogate molecular subtypes of paired primary and lymph node metastatic breast carcinomas,and to explore the value of the GATA3 in pathological diagnosis. Methods Between March 2013 and March 2016, we retrieved 64 cases of paired primary and lymph node metastatic breast carcinomas from the pathology archive at the Meizhou People's Hospital. According to emerging St Gallen2015 Consensus, the four molecular subtypes was divided into A, B, C, D, each types (n=16). Tissue microarrays were created, the sensitivity of monoclonal antibodies to GATA3, GCDFP15 and MGB in different surrogate molecular subtypes of breast carcinoma by using immunohistochemical staining. Staining intensity (0~3+) and extent (0% to 100%) were scored with an H-score calculated (range, 0 to 300). Sensitivities by the H-score cutoffs ≥50 for a positive result in different surrogate molecular subtypes of paired primary and lymph node metastatic breast carcinomas among GATA3, GCDFP15 and MGB. Results GATA3 was significantly more sensitive than GCDFP15 and MGB in breast cancer of A and B type, (P<0.05) rather than C, and D subtype (P>0.05). GATA3 staining had significant differences among different subtypes. GATA3 shows diffuse strong staining in A and B subtypes. GATA3 shows patch low, moderate staining in C and D subtypes. GCDFP15 and MGB staining had no significant differences among different subtypes. Significantly good coincidence was observed between primary and metastatic breast carcinomas. GATA3 expression [kappa value=0.826>0.75] as compared with the coincidence of GCDFP15 [kappa value=0.492<0.75] and MGB [kappa value=0.593<0.75] (P<0.05). Conclusion The matched primary and metastatic tumor expression of GATA3 is good coincidence. GATA3 expression was not the same sensitive as different surrogate molecular subtype of breast cancer. GATA3 expression was superior to GCDFP and MGB in A and B subtypes. GATA3 expression was slight better to GCDFP and MGB in C subtypes. GATA3 expression poorly performed in triple-negative breast cancer. So we need to re-evaluate its diagnostic utility in the hormone receptor negative breast cancer. Especially to the triple-negative breast cancer. -
Key words:
- GATA3 /
- surrogate molecular subtypes of breast carcinomas /
- immunohistochemistry /
- GCDFP15 /
- Mammaglobin
-
图 1 GATA3、GCDFP15、MGB在乳腺癌替代分子分型的表达
A: ER, PR阳性, HER2阴性; B: ER, PR阳性, HER2阳性; C: ER, PR阴性, HER2阳性; D: 三阴; P: 原发性乳腺癌; M: 配对转移性乳腺癌; 1a~8a: H&E染色; 1b~8b: GATA3的免疫组化染色; 1c~8c: GCDFP15的免疫组化染色; 1d~8d: MGB的免疫组化染色; GATA3标记细胞核为黄褐色, GCDFP15标记细胞质为黄褐色, MGB标记细胞膜为黄褐色.
表 1 GATA3、GCDFP15、MGB在乳腺癌替代分子分型的敏感性比较
Types Positive rate（%） χ2 P GATA3 GCDFP15 MGB A Primary 81 31 13 16.609 0.000 Metastasis 81 44 31 8.671 0.013 B Primary 88 13 19 23.087 0.000 Metastasis 81 13 31 16.609 0.000 C Primary 63 19 38 6.284 0.049 Metastasis 50 19 31 3.429 0.206 D Primary 13 25 6 2.139 0.467 Metastasis 13 19 19 0.436 1.000 A: ER, PR阳性, HER2阴性; B: ER, PR阳性, HER2阳性; C: ER, PR阴性, HER2阳性; D: 三阴. 
下载: 导出CSV
表 2 GATA3、GCDFP15、MGB在原发和配对淋巴结转移乳腺癌中表达的一致性
Marker Item MBC Kappa P positive negative total GATA3 PBC positive 47 1 48 0.826 0.000 negative 3 13 16 total 50 14 64 GCDFP15 PBC positive 20 8 28 0.492 0.000 negative 8 28 36 total 28 36 64 MGB PBC positive 17 6 23 0.593 0.000 negative 6 35 41 total 23 41 64 PBC: 原发性乳腺癌; MBC: 配对转移性乳腺癌.
下载: 导出CSV
-
[1] Kouros-Mehr H, Slorach EM, Sternlicht MD, et al. GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland[J]. Cell, 2006, 127(5): 1041-55 doi: 10.1016/j.cell.2006.09.048 [2] Chang A, Amin A, Gabrielson E, et al. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung[J]. Am J Surg Pathol, 2012, 36(10): 1472-6 doi: 10.1097/PAS.0b013e318260cde7 [3] Miettinen M, Mccue PA, Sarlomo-Rikala MA, et al. GATA3: A multispecific but potentially useful marker in surgical pathology a systematic analysis of 2500 epithelial and nonepithelial tumors[J]. Am J Surg Pathol, 2014, 38(1): 13-22 doi: 10.1097/PAS.0b013e3182a0218f [4] Asselin-Labat ML, Sutherland KD, Barker H, et al. Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation[J]. Nat Cell Biol, 2007, 9(2): 201-9 doi: 10.1038/ncb1530 [5] 程 凯, 周晓蝶, 余 波, 等. 乳腺肿瘤组织中GATA3的表达及临床意义[J]. 临床与实验病理学杂志, 2015, 31(7): 725-8 [6] Shield PW, Papadimos DJ, Walsh MD. GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens[J]. Cancer Cytopathol, 2014, 122(4): 307-12 doi: 10.1002/cncy.21393 [7] Krings G, Nystrom M, Mehdi I, et al. Diagnostic utility and sensitivities of GATA3 antibodies in triple-negative breast cancer[J]. Hum Pathol, 2014, 45(11): 2225-32 doi: 10.1016/j.humpath.2014.06.022 [8] Braxton DR, Cohen C, Siddiqui MT. Utility of GATA3 immunohistochemistry for diagnosis of metastatic breast carcinoma in cytology specimens[J]. Diagn Cytopathol, 2015, 43(4): 271-7 doi: 10.1002/dc.v43.4 [9] Sangoi AR, Shrestha B, Yang G, et al. The novel marker GATA3 is significantly more sensitive than traditional markers mammaglobin and GCDFP15 for identifying breast Cancer in surgical and cytology specimens of metastatic and matched primary tumors[J]. Appl Immunohistochem Mol Morphol, 2016, 24(4): 229-37 doi: 10.1097/PAI.0000000000000186 [10] 程 凯, 余 波, 周晓蝶, 等. GATA3在乳腺癌中表达的敏感性和病理诊断的价值[J]. 诊断病理学杂志, 2016, 23(5): 374-7 doi: 10.3969/j.issn.1007-8096.2016.05.018 [11] Huo L, Zhang J, Gilcrease MZ, et al. Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast Cancer[J]. Histopathology, 2013, 62(2): 267-74 doi: 10.1111/his.2012.62.issue-2 [12] Luo MH, Huang YH, Ni YB, et al. Expression of mammaglobin and gross cystic disease fluid protein-15 in breast carcinomas[J]. Hum Pathol, 2013, 44(7): 1241-50 doi: 10.1016/j.humpath.2012.10.009 [13] Wendroth SM, Mentrikoski MJ, Wick MR. GATA3 expression in morphologic subtypes of breast carcinoma: a comparison with gross cystic disease fluid protein 15 and mammaglobin[J]. Ann Diagn Pathol, 2015, 19(1): 6-9 doi: 10.1016/j.anndiagpath.2014.12.001 [14] 江泽飞, 许凤锐. 乳腺癌分子分型对治疗的影响[J]. 中华普外科手术学杂志: 电子版, 2015, 9(6): 12-5 [15] Coates AS, Winer EP, 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): 1533-46 doi: 10.1093/annonc/mdv221 [16] 赵 毅, 邓 鑫. 乳腺癌分子分型与治疗策略[J]. 中国实用外科杂志, 2015, 35(7): 704-8 [17] Banet N, Gown AM, Shih IeM, et al. GATA-3 expression in trophoblastic tissues: an immunohistochemical study of 445 cases, including diagnostic utility[J]. Am J Surg Pathol, 2015, 39(1): 101-8 doi: 10.1097/PAS.0000000000000315 [18] Higgins JP, Kaygusuz G, Wang L, et al. Placental S100 (S100P) and GATA3: markers for transitional epithelium and urothelial carcinoma discovered by complementary DNA microarray[J]. Am J Surg Pathol, 2007, 31(5): 673-80 doi: 10.1097/01.pas.0000213438.01278.5f [19] Tominaga N, Naoi Y, Shimazu K, et al. Clinicopathological analysis of GATA3-positive breast cancers with special reference to response to neoadjuvant chemotherapy[J]. Ann Oncol, 2012, 23(12): 3051-7 doi: 10.1093/annonc/mds120 [20] Parikh P, Palazzo JP, Rose LJ, et al. GATA-3 expression as a predictor of hormone response in breast cancer[J]. J Am Coll Surg, 2005, 200(5): 705-10 doi: 10.1016/j.jamcollsurg.2004.12.025 [21] Voduc D, Cheang M, Nielsen T. GATA-3 expression in breast cancer has a strong association with estrogen receptor but lacks Independent prognostic value[J]. Cancer Epidemiol Biomarkers Prev, 2008, 17(2): 365-73 doi: 10.1158/1055-9965.EPI-06-1090 -
点击查看大图
图(1) / 表(2)
计量
- 文章访问数: 2143
- HTML全文浏览量: 633
- PDF下载量: 2
- 被引次数: 0
