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Combined Detection of CK5/6, CK14 and EGFR in Diagnosis of Basal-like Subtype Triple Negative Breast Cancer
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摘要:
目的 探讨联合检测CK5/6、CK14和表皮生长因子受体(epidermal growth factor receptor, EGFR)对基底样三阴乳腺癌的诊断价值。 方法 北京协和医院2000年1月至2011年12月经组织病理学证实的115例三阴乳腺癌患者, 收集其临床及病理资料。应用免疫组织化学法检测所有石蜡标本中CK5/6, CK14和EGFR的表达, 以此判定是否为基底样三阴乳腺癌。以三者联合检测结果作为金标准, 计算CK5/6, CK14和EGFR单独检测、两两联合检测的敏感性和特异性。进一步分析基底样三阴乳腺癌和非基底样三阴乳腺癌在年龄、肿瘤大小、组织学类型等临床及病理特征方面的差异。 结果 115例三阴乳腺癌患者平均患病年龄为(50.7±13.6)岁。免疫组织化学结果显示, 单独检测CK5/6, 基底样三阴乳腺癌阳性率为29.6%(34/115), CK14为21.7%(18/83), EGFR为60.9%(70/115)。CK14, CK5/6和EGFR三者联合检测阳性率为67.8%(78/115)。将三者联合检测的阳性例数作为金标准, 则EGFR与CK5/6联合检测敏感性及特异性分别可达98.7%及100%。基底样三阴乳腺癌与非基底样三阴乳腺癌在组织学类型、分级, 淋巴结转移情况, 死亡率方面差异有统计学意义(P均 < 0.05), 基底样三阴乳腺癌总生存期显著缩短(HR=0.363, 95% CI:0.139~0.947)。 结论 CK14、CK5/6和EGFR联合检测能够标识出最多数量的基底样三阴乳腺癌。基底样三阴乳腺癌预后比非基底样三阴乳腺癌预后更差, 病理识别很重要。 -
关键词:
- 三阴乳腺癌 /
- 基底样亚型 /
- CK5/6 /
- CK14 /
- 受体, 表皮生长因子
Abstract:Objective To investigate the value of combined detection of CK5/6, CK14 and epidermal growth factor receptor (EGFR) in diagnosing basal-like subtype triple negative breast cancer (TNBC). Methods The clinical and pathological data of 115 patients diagnosed with TNBC were recorded from January 2000 to December 2011. The expression of CK5/6, CK14 and EGFR were detected with immunohistochemical methods using paraffin specimens. Combined detection result of the three markers was used as gold standard, then the sensitivity and specificity of CK5/6, CK14 and EGFR were detected by single marker and two combined assays.The differences between basal-like and non basal-like subtype TNBC in age, tumor size, tumor histological type and other clinicopathological issues were compared. Results The mean age of 115 patients with TNBC was (50.7±13.6) years. Immunhistochemical result showed that single marker positivity was 29.6% (34/115), 21.7% (18/83), and 60.9% (70/115) for CK5/6, CK14, and EGFR, respectively. Combined detection of the three markers, the positive rate was 67.8% (78/115). Taking three markers combination as a golden standard, the sensitivity and specificity of EGFR and CK5/6 combination were 98.7% and 100%. There were significant differences between basal-like and non basal-like subtype TNBC in histological type, tumor grade, lymph node metastasis and mortality(all P < 0.05). Survival analysis showed that the overall survival period of basal-like subtype TNBC was significant shortened(HR=0.363, 95% CI:0.139~0.947). Conclusions Combined detection of CK5/6, CK14 and EGFR could identifiy the largest number of basal-like subtype TNBC. The prognosis of basal-like subtype TNBC is worse than that of non basal-like subtype TNBC, and it is important to identify the subtype. -
Key words:
- triple-negative breast cancer /
- basal-like subtype /
- CK5/6 /
- CK14 /
- epidermal growth factor receptor
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表 1 CK5/6、CK14和EGFR免疫组织化学染色条件
抗体名称 克隆号 稀释倍数 公司 阳性部位 阳性对照 界值 热抗原修复
[1 mmol/L EDTA溶于10 mmol/
LTris缓冲液(pH=8.5)]孵育温度及时间 CK5/6 小鼠单抗(D5/16 B4) 即用型 Dako 膜或浆阳 间皮瘤 ≥5% 100 ℃30 min 37 ℃16 min CK14 兔单抗(SP44) 即用型 Novus 膜或浆阳 头颈癌 ＞5% 100 ℃60 min 37 ℃16 min EGFR 兔单抗(5B7) 即用型 Ventana 膜或浆阳 皮肤 ＞10% 100 ℃30 min 37 ℃16 min EGFR：表皮生长因子受体 
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表 2 CK5/6、CK14、EGFR分别及联合检测基底样三阴乳腺癌的敏感性及特异性
免疫标记物 阳性例数(n) 阴性例数(n) 敏感性(%) 特异性(%) CK5/6 34 81 43.6 45.7 CK14* 18 65 30.5 37 EGFR 70 45 89.7 82.2 EGFR和/或CK5/6 77 38 98.7 100 EGFR和/或CK14 73 42 93.5 88.1 CK5/6和/或CK14 42 73 53.8 50.7 EGFR和/或CK5/6和/或CK14 78 37 100 100 *因组织标本过少，32例无法获取CK14数据；EGFR：同表表 1
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表 3 基底样三阴乳腺癌与非基底样三阴乳腺癌临床及病理特征比较
临床及病理指标 病例数(n) 三阴乳腺癌(n) 基底样 非基底样 P值 年龄 ＜40岁 26 20 6 0.188 ≥40岁 89 58 31 ＜50岁 62 43 19 0.428 ≥50岁 53 35 18 肿瘤大小* ≤3 cm 77 55 22 0.216 ＞3 cm 37 23 14 P53 阳性 48 36 12 0.116 阴性 67 42 25 Ki-67指数** ＞14% 65 47 18 0.315 ≤14% 16 10 6 组织学类型 浸润性导管癌(非特殊类型) 97 70 27 0.023 其他 18 8 10 浸润性导管与小叶混合性癌 3 1 2 髓样癌 4 3 1 黏液癌 2 2 0 浸润性微乳头状癌 2 0 2 浸润性小叶癌 5 1 4 腺鳞癌 2 1 1 分级 1级 10 2 8 2级 35 21 14 0.001 3级 70 55 15 0.001 淋巴结转移情况 阳性 47 37 10 0.029 阴性 68 41 27 复发 有 55 40 15 0.190 无 60 38 22 生存状况 存活 84 52 32 0.019 死亡 31 26 5 *1例肿瘤大小数据缺失；* *由于组织块局限性，34例无法获取Ki-67数据
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