Epidermal growth factor receptor gene mutation, amplification and protein expression in malignant pleural mesothelioma

Epidermal growth factor receptor gene mutation, amplification and protein expression in malignant pleural mesothelioma
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DOI:
10.1007/s00432-008-0384-4
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发表时间:
2008-10-01
影响因子:
3.6
通讯作者:
Fujii, Y.
Fujii, Y.
中科院分区:
医学3区
文献类型:
--
作者:
Okuda, K.;Sasaki, H.;Fujii, Y.

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表皮生长因子受体(EGFR)在多种上皮性恶性肿瘤中过度表达。据报道,在肺癌病例中,EGFR基因激动域的突变和EGFR基因扩增是预测对EGFR酪氨酸激酶抑制剂的反应的指标。在恶性胸膜间皮瘤(MPM)中,EGFR的作用尚不清楚。我们研究了25例日本MPM患者的EGFR基因突变、扩增和蛋白表达。此前没有报道过TaqMan聚合酶链式反应检测到EGFR突变。免疫组织化学检测,8/25例(32%)EGFR蛋白表达阳性。肉瘤型和结缔组织增生型均为阴性。荧光原位杂交分析发现3例低多倍体和1例高多倍体。低多倍体病例包括1例双相型和2个上皮型,高多倍体病例为上皮型。这4例均表达EGFR蛋白。在MPM中,EGFR似乎在有限的患者亚群中发挥作用。为了确定EGFR酪氨酸激酶在抑制剂治疗中的可能候选者,有关EGFR基因状态的信息可能是有价值的。
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies. In lung cancer cases, EGFR gene mutation at the kinase domain and EGFR gene amplification are reported to be predictors of the response to EGFR tyrosine kinase inhibitors. In malignant pleural mesothelioma (MPM), the role of EGFR is less clear. We studied EGFR gene mutation, amplification and protein expression in 25 Japanese patients with MPM. None had previously reported EGFR mutations detected by the TaqMan PCR assay. Using immunohistochemistry, 8/25 (32%) cases were positive for the EGFR protein. The cases of sarcomatous type and desmoplastic type were all negative. Fluorescence in situ hybridization analysis revealed three low polysomy cases and one high polysomy case. The low polysomy cases included one biphasic type and two epithelial types, and the high polysomy case was epithelial type. These four cases expressed EGFR protein. In MPM, EGFR seems to play a role in a limited subset of patients. To identify possible candidates for EGFR tyrosine kinase in inhibitor therapy, the information on the EGFR gene status may be valuable.