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Difference in Clinicopathological Features of Triple Negative Breast Cancer and Non-triple Negative Breast Cancer and Relationship between Clinicopathological Features and Expressions of Estrogen Receptor β/Epidermal Growth Factor Receptor
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摘要:
目的 比较三阴乳腺癌与非三阴乳腺癌在临床病理特征及部分免疫组织化学指标表达上的差异, 并探讨这些免疫组织化学指标的表达与三阴乳腺癌临床病理特征及预后的关系。 方法 2010年1月至2013年12月北京协和医院收治的经组织病理确诊的乳腺癌患者共863例, 其中三阴乳腺癌患者135例, 非三阴乳腺癌患者728例。分析三阴乳腺癌与非三阴乳腺癌患者在发病年龄、病理类型、肿瘤大小、分化程度、肿瘤分期、是否有淋巴结转移、是否累及乳头以及手术方式等临床病理特征方面的差异。通过免疫组织化学法检测135例三阴乳腺癌患者与经单纯抽样法选取的135例非三阴乳腺癌患者中雌激素受体β(estrogen receptor β, ERβ)、表皮生长因子受体(epidermal growth factor receptor, EGFR)、P53、Ki67的表达, 分析上述指标在两类乳腺癌中的表达差异。进一步通过单因素生存分析探讨三阴乳腺癌患者的预后相关因素。 结果 三阴乳腺癌中浸润性导管癌的比例高于非三阴乳腺癌(86.7%比65.2%, P < 0.001), 发病年龄低于非三阴乳腺癌[(46.0±10.6)岁比(51.0±13.3)岁, P < 0.05];三阴乳腺癌与非三阴乳腺癌在淋巴结转移、临床分期、肿瘤大小、分化程度、手术方式方面差异亦有统计学意义(P < 0.05);三阴乳腺癌与非三阴乳腺癌在肿瘤累及乳头的比例差异无统计学意义(P > 0.05)。免疫组织化学结果显示, 三阴乳腺癌中ERβ阳性表达率较非三阴乳腺癌显著降低(63.7%比75.6%, P < 0.05), 而EGFR阳性表达率显著升高(62.2%比33.3%, P < 0.05);P53、Ki67在三阴乳腺癌与非三阴乳腺癌中的表达差异无统计学意义(P > 0.05)。与非三阴乳腺癌相比, 三阴乳腺癌的总体生存率(overall survival, OS)和无复发生存率(relapse-free survival, RFS)更低(P < 0.05)。三阴乳腺癌单因素生存分析结果显示, ERβ阴性表达与EGFR阳性表达均与三阴乳腺癌的不良预后相关(P < 0.05)。 结论 相较于非三阴乳腺癌, 三阴乳腺癌有明显不同的临床病理特征:发病年龄较低、原发肿瘤体积较大、分化程度低、易发生淋巴结转移、ERβ阳性表达率较低、EGFR阳性表达率较高、OS及RFS较低。ERβ和EGFR可能成为重要的三阴乳腺癌预后判断指标。 Abstract:Objective To analyze the differences in clinicopathologic features and expressions of some immunohistochemical indicators between triple negative breast cancer and non-triple negative breast cancer, and to investigate the relationship between clinicopathological features and immunohistochemical indicators. Methods A total of 863 patients (135 triple negative breast cancer and 728 non-triple negative breast cancer) with histopathologically confirmed breast cancer were collected in Peking Union Medical College Hospital from January 2010 to December 2013.We retrospectively analyzed the difference in the onset age, histological subtype, tumor size, tumor differentiation, tumor stages, lymph node metastasis, nipple involvement and operation method between triple negative breast cancer and non-triple negative breast cancer, then explored the difference between them in the expressions of estrogen receptor β (ERβ), epidermal growth factor receptor (EGFR), P53, and Ki67 by immunohistochemical staining. Prognostic factors of triple negative breast cancer were further discussed by univariate survival analysis. Results The proportion of invasive ductal carcinoma in triple negative breast cancer was higher than that in non-triple negative breast cancer (86.7% vs. 65.2%, P < 0.001); the age of onset was younger in triple negative breast cancer[(46.0±10.6) years vs. (51.0±3.3) years, P < 0.05];significant differences were also found in lymph node metastasis, tumor size, differentiation grade, surgical procedure, and tumor stages between the two groups(P < 0.05); no statistically significant inter-group difference in nipple involvement (P > 0.05). Immunohistochemical results showed that compared with non-triple negative breast cancer, ERβ expression rate decreased significantly(63.7% vs. 75.6%, P < 0.05)while EGFR expression rate increased significantly in triple negative breast cancer(62.2% vs. 33.3%, P < 0.05); the expression of P53 and Ki67 demonstrated no significant difference(P > 0.05). The overall survival(OS)and relapse-free survival(RFS)were both lower in triple negative breast cancer(P < 0.05). Univariate survival analysis showed that both ERβ negative expression and EGFR positive expression were related to the poor prognosis of triple negative breast cancer (P < 0.05). Conclusions Compared with non-triple negative breast cancer, triple negative breast cancer shows completely different clinicopathological features:younger age of onset, larger tumor size, lower degree of differentiation, higher incidence of lymph node metastasis, lower ERβ expression, higher EGFR expression, and lower OS and RFS.ERβ and EGFR may be important prognostic indicators in triple negative breast cancer. -
表 1 三阴乳腺癌与非三阴乳腺癌患者的临床病理特征比较[例(%)]
病理分型 发病年龄(岁) 家族史 病理类型 淋巴结状态 是否累及乳头 临床分期 肿瘤最大直径(cm) 分化程度 手术方式 ≤35 ＞35 有 无 浸润性导管癌 其他 阳性 阴性 是 否 Ⅰ期 Ⅱ期 Ⅲ期 ≤2 2~5 ≥5 高分化 中分化 低分化 改良根治术 其他 三阴乳腺癌
(n=135)18(13.3) 117(86.7) 10(7.4) 125(92.6) 117(86.7) 18(13.3) 76(56.3) 59(43.7) 4(3.0) 131(97.0) 35(25.9) 95(70.4) 5(3.7) 35(25.9) 95(70.4) 5(3.7) 21(15.5) 58(43.0) 56(41.5) 86(63.7) 49(36.3) 非三阴乳腺癌
(n=728)52(7.1) 676(92.9) 18(2.5) 710(97.5) 475(65.2) 253(34.8) 218(29.9) 510(70.1) 15(2.1) 713(97.9) 260(35.7) 418(57.4) 50(6.9) 260(35.7) 418(57.4) 50(6.9) 116(15.9) 424(58.2) 188(25.8) 587(80.6) 141(19.4) χ2值 5.855 8.835 24.255 35.206 0.431 8.196 8.196 14.645 19.008 P值 0.016 0.003 < 0.001 < 0.001 0.512 0.017 0.017 0.001 < 0.001 
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表 2 三阴乳腺癌与非三阴乳腺癌患者的免疫组织化学指标表达差异[例(%)]
病理分型 ERβ EGFR 病理类型 P53 Ki67 (-) (+) (++) (+++) (-) (+) (++) (+++) (-) (+) (-) (+) (++) (+++) 三阴乳腺癌(n=135) 49(36.3) 64(47.4) 20(14.8) 2(1.5) 51(37.8) 30(22.2) 37(27.4) 17(12.6) 三阴乳腺癌(n=135) 51(37.8) 84(62.2) 29(21.5) 26(19.3) 30(22.2) 50(37.0) 非三阴乳腺癌(n=135) 33(24.4) 59(43.7) 27(20.0) 16(11.9) 90(66.7) 12(8.9) 7(5.2) 26(19.3) 非三阴乳腺癌(n=135) 62(45.9) 73(54.1) 26(19.3) 76(56.3) 16(11.9) 17(12.6) χ2值 4.484 22.578 χ2值 1.841 0.205 P值 0.034 < 0.001 P值 0.175 0.650 ERβ：雌激素受体β；EGFR：表皮生长因子受体
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表 3 三阴乳腺癌患者ERβ表达与临床病理特征的关系[例(%)]
ERβ表达 发病年龄(岁) 家族史 淋巴结状态 是否累及乳头 临床分期 肿瘤最大直径(cm) 分化程度 P53 Ki67 EGFR ≤35 ＞35 有 无 阳性 阴性 是 否 Ⅰ期 Ⅱ期 Ⅲ期 ≤2 2~5 ≥5 高分化 中分化 低分化 (-) (+) (-) (+) (-) (+) 阴性(n=49) 11(22.4) 38(77.6) 4(8.2) 45(91.8) 41(83.7) 8(16.3) 2(4.1) 47(95.9) 3(6.1) 43(87.8) 3(6.1) 3(6.1) 43(87.8) 3(6.1) 3(6.1) 15(30.6) 31(63.3) 21(42.9) 28(57.1) 15(30.6) 34(69.4) 31(63.3) 18(36.7) 阳性(n=86) 7(8.1) 79(91.9) 2(2.3) 84(97.7) 35(40.7) 51(59.3) 2(2.3) 84(97.7) 32(37.2) 52(60.5) 2(2.3) 32(37.2) 52(60.5) 2(2.3) 18(20.9) 43(50.0) 25(29.1) 30(34.9) 56(65.1) 14(16.3) 72(83.7) 20(23.3) 66(76.7) χ2值 5.531 8.920 23.432 0.335 16.154 16.154 15.930 0.844 3.802 0.844 P值 0.019 0.003 < 0.001 0.563 < 0.001 < 0.001 < 0.001 0.358 0.051 < 0.001 ERβ、EGFR：同表 2
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