c-Met、VEGF、EGFR和HER-2在AFP阳性胃癌中的表达研究

方　瑜; 王　琳; 李桂梅

doi:10.19401/j.cnki.1007-3639.2016.08.004

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c-Met、VEGF、EGFR和HER-2在AFP阳性胃癌中的表达研究

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- c-Met、VEGF、EGFR和HER-2在AFP阳性胃癌中的表达研究
- The expressions of c-Met, VEGF, EGFR and HER-2 in the AFP-producing gastric cancer
- 中国癌症杂志 2016年26卷第8期页码：662-669
- 作者机构：
  
  1. 南京解放军八一医院全军肿瘤中心肿瘤内科,江苏,南京,210002
  2. 安徽省第二人民医院肿瘤科,安徽,合肥,231000
  3. 南京解放军八一医院病理科,江苏,南京,210002
- 作者简介：
- 基金信息：
  
  中国胃肠肿瘤临床研究协作组胃癌研究基金(20130101002)。
- DOI：10.19401/j.cnki.1007-3639.2016.08.004
  中图分类号：
- 网络出版：2016-10-19，
  
  纸质出版：2016-10-19
- 稿件说明：
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方　瑜,王　琳,李桂梅,等. c-Met、VEGF、EGFR和HER-2在AFP阳性胃癌中的表达研究[J]. 中国癌症杂志, 2016, 26(8): 662-669.

方　瑜, 王　琳, 李桂梅. The expressions of c-Met, VEGF, EGFR and HER-2 in the AFP-producing gastric cancer[J]. China Oncology, 2016, 26(8): 662-669.
方　瑜,王　琳,李桂梅,等. c-Met、VEGF、EGFR和HER-2在AFP阳性胃癌中的表达研究[J]. 中国癌症杂志, 2016, 26(8): 662-669. DOI： 10.19401/j.cnki.1007-3639.2016.08.004.

方　瑜, 王　琳, 李桂梅. The expressions of c-Met, VEGF, EGFR and HER-2 in the AFP-producing gastric cancer[J]. China Oncology, 2016, 26(8): 662-669. DOI： 10.19401/j.cnki.1007-3639.2016.08.004.

摘要

背景与目的：甲胎蛋白(alpha fetoprotein，AFP)阳性胃癌(AFP-producing gastric carcinoma，AFPGC)被认为是一种特殊类型的胃癌。疗效比普通胃癌差。针对此类胃癌，探寻其临床病理特征，可能对AFPGC的诊断及个体化治疗具有十分重要的意义。该研究旨在探讨肝细胞生长因子受体c(c-Met)、血管内皮生长因子(vascular endothelial growth factor，VEGF)、表皮生长因子受体(epidermal growth factor receptor，EGFR)和人表皮生长因子受体2(human epidermal growth factor receptor-2，HER-2)等分子标志物在AFPGC中的表达。方法：收集临床上AFPGC(AFP≥10 μg/L)组织标本共44例，其中AFP≥200 μg/L者共30例，同时收集与该30例AFPGC临床分期基本一致的30例AFP正常胃癌及30例AFP升高(AFP≥200 μg/L)的肝细胞癌组织蜡块作为两个对照组，通过免疫组织化学法(EnVision染色方法)检测其c-Met、VEGF、EGFR和HER-2的表达，并通过标记CD34，计数肿瘤微血管密度(microvessel density，MVD)，比较3组肿瘤c-Met、VEGF、EGFR、HER-2和MVD表达的异同。主要收集患者的性别、年龄、血清中AFP最高水平、分化程度、肿瘤分期、肿瘤部位、淋巴结转移、肝转移和Lauren分型等临床病例资料，分析AFPGC患者的临床病理特征。结果：AFPGC临床病理特征显示，44例AFPGC组，淋巴结转移率为86.36%(38/44)，肝转移率为54.55%(24/44)，Lauren分型肠型为36.36%(16/44)，弥漫型为56.82%(25/44)，混合型为6.82%(3/44)。AFPGC组、AFP正常胃癌组和AFP升高肝细胞癌组c-Met蛋白的阳性表达率分别为73.33%(22/30)、70.00%(21/30)和53.33%(16/30)，VEGF蛋白的阳性表达率分别为76.67%(23/30)、56.67%(17/30)和66.67%(20/30)，EGFR蛋白的阳性表达率分别为53.33%(16/30)、40.00%(12/30)和73.33%(22/30)。HER-2“++~+++”在AFPGC组、AFP正常胃癌组和AFP升高肝细胞癌组中所占比例分别为36.67%(11/30)、23.33%(7/30)和26.67%(8/30)。MVD值在AFPGC组、AFP正常胃癌组与AFP升高肝细胞癌组中分别为23.03±10.24、21.92±11.45和19.43±7.83。与AFP正常胃癌组相比，AFPGC组的VEGF蛋白表达明显高于前者(P＜0.05)；与AFP升高的肝细胞癌组相比，AFPGC组的c-Met蛋白表达明显高于前者(P＜0.05)。结论：AFPGC易发生淋巴结及肝转移，Lauren分型以弥漫型为主。与AFP正常胃癌相比较，AFPGC中VEGF蛋白存在过表达；与AFP升高肝细胞癌相比较，AFPGC组织中c-Met蛋白存在过表达。

Abstract

Background and purpose: Alpha fetoprotein (AFP)-producing gastric cancer (AFPGC) is considered to be a special type of gastric cancer. Currently

the effect on AFPGC is not as good as the common AFP-negative gastric cancer. Therefore

it is very important to explore clinicopathological features of AFPGC cancer

to improve diagnosis and individualized treatment. This study is to investigate the expressions of hepatocyte growth factor receptor c (c-Met)

vascular endothelial growth factor (VEGF)

epidermal growth factor receptor (EGFR)

human epidermal growth factor receptor 2 (HER-2) in the AFPGC. Methods: A total number of 44 cases of AFPGC (serum AFP≥10 μg/L) tissues were selected as a test group. There were 30 cases of serum AFP≥200 μg/L. This study collected 30 cases of gastric cancer with normal AFP and 30 cases of hepatocellular carcinoma with increased AFP (serum AFP≥200 μg/L) as 2 control groups. The cases of the 3 groups had the same clinical stage basically. The expressions of c-Met

VEGF

EGFR and HER-2

CD34 were detected by immunohistochemistry (EnVision staining method). Tumor microvessel density (MVD) was calculated by marking CD34

and the results were analyzed. The clinicopathologic parameters were recorded accurately: gender

age

highest level of serum AFP

tumor differentiation

tumor stage

tumor location

lymph node metastasis

liver metastasis

Lauren classification

etc. These patients were followed up regularly. The clinical pathological features of AFPGC patients were investigated. Results: AFPGC clinical characteristics showed that

among 44 cases of AFPGC group

86.36% (38/44) had lymph node metastasis

54.55% (24/44) had hepatic metastasis

intestinal type was 36.36% (16/44)

diffuse type was 56.82% (25/44)

mixed type was 6.82% (3/44). The positive expression rates of c-Met protein in AFPGC

gastric cancer with normal AFP

hepatocellular carcinoma with increased AFP were 73.33% (22/30)

70.00% (21/30) and 53.33% (16/30)

respectively. The positive expression rates of VEGF protein were 76.67% (23/30)

56.67% (17/30) and 66.67% (20/30)

respectively. The positive expression rates of EGFR protein were 53.33% (16/30)

40.00% (12/30) and 73.33% (22/30)

respectively. The “++ and +++” expression rates of HER-2 in AFPGC

gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 38.64% (17/44)

23.33% (7/30) and 26.67% (7/30)

respectively. The MVD values in AFPGC

gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 23.03±10.24

21.92±11.45 and 19.43±7.83

respectively. Compared with gastric cancer with normal AFP

expression of VEGF protein was significantly higher in the AFPGC (P0.05). Compared with hepatocellular carcinoma with increased AFP

the expression of c-Met protein was significantly higher in AFPGC (P0.05). Conclusion: AFPGC is prone to lymph node metastasis and hepatic metastasis. The major part is the diffuse type in Lauren classification. The positive expression rates of VEGF protein in AFPGC were significantly higher than the gastric cancer with normal AFP. The positive expression rates of c-Met protein in AFPGC were significantly higher than the hepatocellular carcinoma with AFP increased.

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