Association of c-Met phosphorylation with micropapillary pattern and small cluster invasion in pT1-size lung adenocarcinoma
Association of c-Met phosphorylation with micropapillary pattern and small cluster invasion in pT1-size lung adenocarcinoma
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DOI：
10.1016/j.lungcan.2013.09.005
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发表时间：
2013-12-01
期刊：
影响因子：
5.3
通讯作者：
Nabeshima, Kazuki
中科院分区：
文献类型：
--
作者：
Koga, Kaori;Hamasaki, Makoto;Nabeshima, Kazuki
具有微乳头状模式（MPP）的肺腺癌与频繁的淋巴结转移相关。然而，人们对 MPP 相关淋巴结转移的机制知之甚少。我们之前报道过，伴有 MPP 的 pT1 肺腺癌与小簇侵犯 (SCI) 和淋巴受累显着相关。 SCI 被定义为明显消退的腺泡乳头状肿瘤结构，单个或小簇癌细胞侵入纤维化病灶内的间质。在本研究中，我们假设 c-Met 激活可能参与 MPP-SCI 序列，因为 c-Met 酪氨酸激酶受体及其配体肝细胞生长因子 (HGF) 在肿瘤细胞运动和侵袭中发挥重要作用。我们分析了 125 个 pT1 大小的肺腺癌中磷酸化 c-Met 的免疫组织化学表达及其与 MPP、SCI、淋巴受累和预后的相关性。 MPP 阳性组中 SCI 的发生率明显更高 (P < 0.0001)，并且与淋巴受累 (P < 0.0001) 和淋巴结转移 (P = 0.021) 相关。通过免疫组织化学膜和细胞质染色在所有肿瘤中检测到 c-Met 蛋白。 Phospho-c-Met (pc-Met) 在 119/125 个肿瘤 (95%) 中呈阳性，并在 27 个病例 (22%) 中高水平表达。高水平的 pc-Met 表达与 MPP (P = 0.01) 和 SCI (P = 0.0059) 显着相关。此外，在 MPP 或 SCI 肿瘤中，表达高水平 pc-Met 的肿瘤与淋巴受累的相关性显着更高。在 p-IA 期肺腺癌 (n = 99) 中，高 pc-Met 表达组患者的生存率明显低于低表达组患者 (P = 0.0313)。这些结果表明，通过磷酸化激活 c-Met 可能参与 MPP 和 SCI。 (C) 2013 Elsevier Ireland Ltd. 保留所有权利。
Lung adenocarcinomas with micropapillary pattern (MPP) are associated with frequent nodal metastasis. However, little is known about the mechanisms that underlie MPP-associated nodal metastasis. We have previously reported that pT1 lung adenocarcinomas with MPP are significantly associated with small cluster invasion (SCI) and lymphatic involvement. SCI is defined as markedly resolved acinar-papillary tumor structures with single or small clusters of carcinoma cells invading stroma within fibrotic foci. In this study, we hypothesized that c-Met activation may be involved in the MPP-SCI sequence, given that the c-Met tyrosine-kinase receptor and its ligand hepatocyte growth factor (HGF), play important roles in tumor cell motility and invasion. We analyzed 125 pT1-size lung adenocarcinomas for immunohistochemical expression of phosphorylated c-Met and its correlation with MPP, SCI, lymphatic involvement and prognosis. SCI was significantly more frequent in the MPP-positive group (P < 0.0001) and associated with lymphatic involvement (P < 0.0001) and nodal metastasis (P = 0.021). c-Met protein was detected in all tumors by immunohistochemistry as membranous and cytoplasmic staining. Phospho-c-Met (pc-Met) was positive in 119/125 tumors (95%) and expressed at high levels in 27 cases (22%). A high level of pc-Met expression was significantly associated with MPP (P = 0.01) and SCI (P = 0.0059). Moreover, in tumors with MPP or SCI, those expressing high levels of pc-Met were significantly more associated with lymphatic involvement. In p-Stage IA lung adenocarcinomas (n = 99), patients in the high pc-Met expression group showed significantly worse survival than patient in the low expression group (P = 0.0313). These results suggest that activation of c-Met through phosphorylation may be involved in MPP and SCI. (C) 2013 Elsevier Ireland Ltd. All rights reserved.