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原发性结直肠癌肿瘤中的表皮生长因子受体(EGFR)状态与相关转移部位的EGFR表达不相关:对EGFR靶向单克隆抗体治疗的启示。

Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies.

作者信息

Scartozzi Mario, Bearzi Italo, Berardi Rossana, Mandolesi Alessandra, Fabris Guidalberto, Cascinu Stefano

机构信息

Clinica di Oncologia Medica, Istituto di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti, Ancona, Italy.

出版信息

J Clin Oncol. 2004 Dec 1;22(23):4772-8. doi: 10.1200/JCO.2004.00.117.

Abstract

PURPOSE

We hypothesized that the detection of epidermal growth factor receptor (EGFR) expression performed in primary tumors for treatment with EGFR-targeted monoclonal antibodies could not always correlate with EGFR status in metastatic sites, thus making cancer cells in these sites resistant to therapy. The aim of our study was to correlate EGFR expression on primary tumors and related metastases in order to find out whether assessing EGFR status on primary cancer is to be considered an effective tool for planning treatment with EGFR-targeted antibodies.

PATIENTS AND METHODS

We retrospectively evaluated EGFR immunohistochemistry from primary tumors and related metastatic sites in 99 colorectal cancer patients. The site of primary tumor was colon in 77 patients (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84 patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in five patients (5%). EGFR status was defined as positive if the percentage of malignant cells stained was > or = 1%.

RESULTS

EGFR status was positive in 53 primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the corresponding metastatic site was found negative, whereas it was found positive in seven metastases (15%) from EGFR-negative primary cancers. The difference between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR-negative to EGFR-positive) was statistically significant (P = .036).

CONCLUSION

Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).

摘要

目的

我们推测,在原发性肿瘤中检测表皮生长因子受体(EGFR)表达以用于EGFR靶向单克隆抗体治疗时,其结果可能并不总是与转移部位的EGFR状态相关,从而导致这些部位的癌细胞对治疗产生抗性。我们研究的目的是将原发性肿瘤与相关转移灶的EGFR表达进行关联,以确定评估原发性癌症的EGFR状态是否应被视为规划EGFR靶向抗体治疗的有效工具。

患者与方法

我们回顾性评估了99例结直肠癌患者原发性肿瘤及相关转移部位的EGFR免疫组化情况。原发性肿瘤位于结肠的患者有77例(78%),位于直肠的患者有22例(22%)。分析的转移部位包括84例患者的肝脏(81%)、13例患者的肺(13%)、1例患者的骨(1%)和5例患者的脑(5%)。若染色的恶性细胞百分比≥1%,则EGFR状态定义为阳性。

结果

53例原发性肿瘤(53%)的EGFR状态为阳性。在19例表达EGFR的原发性肿瘤中(36%),相应的转移部位为阴性,而在7例来自EGFR阴性原发性癌症的转移灶中(15%)发现为阳性。这两组患者(即EGFR阳性与EGFR阴性对EGFR阴性与EGFR阳性)之间的差异具有统计学意义(P = 0.036)。

结论

我们的结果表明,在相当比例的EGFR阳性和阴性原发性肿瘤中(分别为36%和15%),检测原发性结直肠癌中的EGFR可能不足以用于规划EGFR靶向单克隆抗体治疗。

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