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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Association of c-Met phosphorylation with micropapillary pattern and small cluster invasion in pT1-size lung adenocarcinoma
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Association of c-Met phosphorylation with micropapillary pattern and small cluster invasion in pT1-size lung adenocarcinoma

机译：pT1大小肺腺癌中c-Met磷酸化与微乳头模式和小簇侵袭的关系

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摘要

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.
机译：具有微乳头状（MPP）的肺腺癌与频繁的淋巴结转移有关。然而，对于与MPP相关的淋巴结转移的基础机制知之甚少。我们以前曾报道过，MPT的pT1肺腺癌与小簇浸润（SCI）和淋巴管浸润显着相关。 SCI被定义为明显分辨的腺泡-乳头状肿瘤结构，其中单个或小的癌细胞侵袭纤维化灶内的基质。在这项研究中，我们假设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起重要作用，因此c-Met激活可能与MPP-SCI序列有关。 。我们分析了125 pT1大小的肺腺癌的磷酸化c-Met的免疫组织化学表达及其与MPP，SCI，淋巴管浸润和预后的关系。 MPP阳性组中SCI的发生率显着更高（P <0.0001），并与淋巴受累（P <0.0001）和淋巴结转移有关（P = 0.021）。通过免疫组织化学，通过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肿瘤中呈阳性（95％），在27例中高表达（22％）。高水平的pc-Met表达与MPP（P = 0.01）和SCI（P = 0.0059）显着相关。此外，在患有MPP或SCI的肿瘤中，表达高水平pc-Met的肿瘤与淋巴受累的相关性更高。在p-Stage IA肺腺癌（n = 99）中，高pc-Met表达组的患者生存率显着低于低表达组（p = 0.0313）。这些结果表明，MPP和SCI可能通过磷酸化激活c-Met。

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