Prognostic significance of phosphorylated p38 mitogen-activated protein kinase and HER-2 expression in lymph node-positive breast carcinoma
Prognostic significance of phosphorylated p38 mitogen-activated protein kinase and HER-2 expression in lymph node-positive breast carcinoma
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DOI：
10.1002/cncr.11940
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发表时间：
2004-02-01
期刊：
影响因子：
6.2
通讯作者：
Bacus, SS
中科院分区：
文献类型：
--
作者：
Esteva, FJ;Sahin, AA;Bacus, SS
背景化疗诱导的p38丝裂原活化蛋白激酶（MAPK）磷酸化导致乳腺癌细胞凋亡增加。本研究的目的是评估活化磷酸化p38 MAPK（P-p38）在浸润性乳腺癌中的表达率，P-p38 MAPK表达与HER-2的相关性，并评估该标志物在淋巴结阳性乳腺癌辅助化疗患者中的预后价值。采用免疫组化法检测96例淋巴结阳性乳腺癌患者化疗前后P-p38、HER-2和Ki-6的表达。在开始辅助化疗之前，在原发肿瘤中测量所有标记物。中位随访期为首次癌症手术后11年。视觉评分P-p38 MAPK表达并使用图像分析仪定量。P-p38 MAPK表达率范围为19- 24%，取决于所用的评分系统。肿瘤表达高水平P-p38 MAPK的患者的无进展生存期（PFS）有缩短的趋势，尽管差异无统计学意义（P = 0.39）。P-p38 MAPK过表达和Ki-67高表达患者的PFS较短（P = 0.04）。在HER-2阴性患者中，P-p38 MAPK过表达与PFS缩短相关（P = 0.05）。P38 MAPK磷酸化发生在20%的原发性乳腺癌中，可能与淋巴结阳性乳腺癌患者的预后不良有关。P-p38 MAPK与HER-2在乳腺癌中的相互作用尚需进一步研究。
BACKGROUND. Chemotherapy-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation reportedly leads to increased apoptosis in breast carcinoma cells. The goals of the current study were to assess the incidence of activated phosphorylated p38 MAPK (P-p38) expression in invasive breast carcinoma, correlate expression of P-p38 MAPK with HER-2, and estimate the prognostic value of this marker in patients with lymph node-positive breast carcinoma treated with adjuvant chemotherapy.METHODS. P-p38, HER-2, and Ki-6 were measured using immunohistochemistry (peroxidase method) in 96 patients with lymph node-positive breast carcinoma treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. All markers were measured in the primary tumors, before the initiation of adjuvant chemotherapy. The median follow-up period was 11 years after initial cancer surgery. P-p38 MAPK expression was scored visually and quantified using an image analyzer.RESULTS. The rate of P-p38 MAPK expression ranged from 19-24%, depending on the scoring system used. There was a trend toward shorter progression-free survival (PFS) for patients whose tumors expressed high levels of P-p38 MAPK, although the difference was not statistically significant (P = 0.39). PFS was shorter in patients whose tumors overexpressed P-p38 MAPK and had a high level of Ki-67 (P = 0.04). In HER-2-negative patients, P-p38 MAPK overexpression was associated with a shorter PFS (P = 0.05).CONCLUSIONS. P38 MAPK phosphorylation occurred in 20% of primary breast carcinomas and may be associated with poor outcome in patients with lymph node-positive breast carcinoma. Further studies are needed to define the interaction between P-p38 MAPK and HER-2 expression in breast carcinoma.