原发性结直肠癌及相关转移部位中生物学关键调节因子的共表达：对西妥昔单抗治疗的意义。

Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab.

作者信息

Barbier A, Domont J, Magné N, Goldmard J-L, Genestie C, Hannoun C, Vaillant J-C, Bellanger A, Khayat D, Capron F, Spano J-P

机构信息

Département d'anatomopathologie, groupe hospitalier Pitié-Salpêtrière, Paris, France.

出版信息

Bull Cancer. 2010 Feb;97(2):E9-E15. doi: 10.1684/bdc.2010.1033.

DOI:10.1684/bdc.2010.1033

PMID:20085858

Abstract

BACKGROUND

Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases.

METHODS

Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested.

RESULTS

Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036).

CONCLUSION

Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.

摘要

背景

近期研究表明，结直肠癌（CRC）中原发肿瘤与转移灶在表皮生长因子受体（EGFR）表达方面存在显著差异。本研究旨在关联原发性CRC样本与转移灶之间一组分子标志物的表达情况。

方法

对46例CRC患者经福尔马林固定、石蜡包埋的切片进行免疫组织化学分析，检测28例原发性肿瘤和32例肝转移灶中EGFR、磷酸化EGFR（pEGFR）、血管内皮生长因子（VEGF）、磷酸化VEGF（pVEGF）、第10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）、磷酸化蛋白激酶B（pAKT）和p21的表达。通过组织微阵列评估分子谱。检测肿瘤与转移灶生物标志物表达之间的相关性。

结果

在60例CRC样本中，25%的样本EGFR呈阳性，38%的样本pEGFR呈阳性，38%的样本VEGF呈阳性，48%的样本pVEGF呈阳性，70%的样本pAKT呈阳性，51%的样本p21呈阳性。39%的病例PTEN缺失，49%的病例未发现p21表达。原发性肿瘤与转移灶在pAKT（p = 0.037）和pEGFR（p = 0.0002）状态方面存在显著相关性。在接受西妥昔单抗治疗的患者（n = 18）中，p21是反应的显著预测因子（p = 0.036）。