目的探讨NF—κB、雌激素受体(ER)、人上皮细胞生长因子受体-2(HER2)和增殖细胞核抗原(PCNA)等在乳腺癌中的蛋白表达特征,以及NF—κB活化与乳腺癌的ER、HER2、PCNA表达水平以及肿瘤淋巴结转移、肿瘤大小和组织学分级等临床病理学指标之间的相关性。方法采用免疫组化方法对60例乳腺癌和对应的癌旁组织的NF—κB、ER、HER2和PCNA等分子标志物的表达情况进行检测分析,同时收集对应的临床病理学数据。结果60例乳腺癌和癌旁组织的NF—κB活化率分别为50.0%(30/60)和40.0%(24/60)。乳腺癌与对应的癌旁组织的NF-κB活化率差异无显著性(P〉0.05)。乳腺癌组织中的NF-κB活化与HER2表达呈正相关,与ER表达呈负相关。ER阴性/HER2阳性组的乳腺癌组织的NF-κB活化率为77.8%(14/18),明显高于其他组(P〈0.001)。组织学分化低级别的乳腺癌组织的NF—κB活化率分别为57.1%(Ⅲ级)和50.3%(Ⅱ级),明显高于高分化组35.7%(Ⅰ级)(P〈0.05)。乳腺癌组织的NF—κB活化率也与其大小和淋巴结转移相关,同时也与乳腺癌细胞的PCNA表达水平相关。结论乳腺癌的演化过程中有不同程度的NF-κB活化,但与HER2表达呈正相关,与ER表达呈负相关。NF—κB具有促进增殖和迁移、抑制分化和凋亡的作用,是乳腺癌形成过程中的一个发生失调的分子,可能成为抗癌治疗的靶位。
Objective To invcstigate the expression of nuclear transcription factor NF-κB,estrogen receptor (ER) , HER2 and PCNA in breast cancer, and the relationship between activation of NF-κB and clinicopathologic parameters including the level of PCNA, ER, HER2,lymph node involvement, tumor size and histological grade ( differentiation). Methods Sixty cases of human breast cancer tissues and adjacent non-neoplastic breast tissues were examined for NF-κB, HER2 and ER, as well as PCNA by immunohistochemical methods. In addition to the clinicopathologic parameters of the patients including lymph node involvement, tumor size and histological grade ( differentiation) were collected. Results The expression of NF-κB in the breast cancers and adjacent non-neoplastic breast tissue was 50.0% ( 30/60 ) and 40. 0% ( 24/60 ) respectively, resulting in no significance ( P 〉 0.05 ). NF-κB activation was positively correlated with HER2 cxpression whereas negatively correlated with ER expression. The NF-κB activation was 77.8% ( 14/18 ) in the breast cancers that were ER-/HER2 +, significantly higher ( P 〈 0.001 ) in comparison to the other groups of patients. The expression of NF-κB in the low-differentiated group ( grade Ⅲ ) was 57. 1% ,and in the moderate-differentiated group (grade Ⅱ ) was 50.3% ,both of which were higher than 35.7% found in the high-differentiated group ( grade Ⅰ ). NF-κB activation in the cancers was significantly correlated with the histological grade,PCNA expression and lymph node involvement and tumor size. Conclusion NF-κB is activated in part of the breast canccrs but it is positively correlated with HER2 expression, and negatively correlated with the level of ER, which can promote proliferation and migration and inhibit differentiation and apoptosis. NF-κB may be a hopeful target for breast cancer therapy.