食管鳞癌中表皮生长因子受体过表达与表皮生长因子受体基因拷贝数增加的相关性。
Correlation of epidermal growth factor receptor overexpression with increased epidermal growth factor receptor gene copy number in esophageal squamous cell carcinomas.
机构信息
Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
出版信息
Chin Med J (Engl). 2012 Feb;125(3):450-4.
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies in China and epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane. The aim of this study was to investigate the protein overexpression and gene copy number of EGFR in ESCC, and help to identify patients who may benefit from EGFR targeted therapies.
METHODS
Immunohistochemistry (IHC) was performed to analyze the expression of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 cases of normal esophageal tissue. Fluorescence in situ hybridization (FISH) was performed to analyze the gene copy number in 80 cases of ESCC, eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue.
RESULTS
The IHC-positive rates of EGFR in 105 cases of ESCC, 16 cases of squamous epithelial atypical hyperplasia, and 11 normal esophageal tissues were 97% (102/105), 44% (7/16), and 18% (2/11) respectively. The difference in the expression of EGFR among different esophageal tissue groups had statistically significance (P < 0.05). Among the 105 cases of ESCC, overexpression of EGFR was found in 90 cases (86%), of which 55 cases scored 3+ for EGFR staining and 35 cases scored 2+. In ESCC, the expression of EGFR was significantly correlated with depth of invasion and TNM stage (P < 0.05), but not with other parameters. The FISH-positive rates of EGFR in 80 cases of ESCC, the eight cases of squamous epithelial atypical hyperplasia, and eight samples of normal esophageal tissue were 31.3% (25/80), 0 (0/8) and 0 (0/8) respectively. In ESCC, EGFR gene amplification was found in 17 (21%) cases, high polysomy in 8 (10%) cases, disomy in 34 cases, low trisomy in 17 cases, and high trisomy in four cases. EGFR FISH-positive was significantly correlated with depth of invasion and lymph node metastasis (P < 0.05). EGFR FISH-positive was significantly associated with overexpression of EGFR.
CONCLUSION
Protein overexpression and/or increased gene copy number of EGFR is common in ESCC, and EGFR targeted therapy may be appropriate for ESCC patients.
背景
食管鳞状细胞癌（ESCC）是中国最常见的恶性肿瘤之一，表皮生长因子受体（EGFR）广泛分布于人类上皮细胞膜。本研究旨在探讨 ESCC 中 EGFR 的蛋白过表达和基因拷贝数，以帮助识别可能受益于 EGFR 靶向治疗的患者。
方法
采用免疫组织化学（IHC）分析 105 例 ESCC、16 例鳞状上皮不典型增生和 11 例正常食管组织中 EGFR 的表达。采用荧光原位杂交（FISH）分析 80 例 ESCC、8 例鳞状上皮不典型增生和 8 例正常食管组织的基因拷贝数。
结果
105 例 ESCC、16 例鳞状上皮不典型增生和 11 例正常食管组织中 EGFR 的 IHC 阳性率分别为 97%（102/105）、44%（7/16）和 18%（2/11）。不同食管组织组 EGFR 的表达差异有统计学意义（P<0.05）。在 105 例 ESCC 中，发现 EGFR 过表达 90 例（86%），其中 EGFR 染色评分 3+者 55 例，评分 2+者 35 例。在 ESCC 中，EGFR 的表达与浸润深度和 TNM 分期显著相关（P<0.05），但与其他参数无关。80 例 ESCC、8 例鳞状上皮不典型增生和 8 例正常食管组织的 EGFR FISH 阳性率分别为 31.3%（25/80）、0（0/8）和 0（0/8）。在 ESCC 中，发现 EGFR 基因扩增 17 例（21%），高倍体 8 例（10%），二倍体 34 例，低三倍体 17 例，高三倍体 4 例。EGFR FISH 阳性与浸润深度和淋巴结转移显著相关（P<0.05）。EGFR FISH 阳性与 EGFR 过表达显著相关。
结论
ESCC 中 EGFR 的蛋白过表达和/或基因拷贝数增加较为常见，EGFR 靶向治疗可能适用于 ESCC 患者。
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