Wang Jayson, Hollingshead James, El-Masry Nabil, Horncastle Donna, Talbot Ian, Tomlinson Ian, Alison Malcolm R, El-Bahrawy Mona
Department of Histopathology, Imperial College London, Hammersmith Hospital, DuCane Road, London, W12 0NN, UK.
J Gastrointest Cancer. 2012 Sep;43(3):444-55. doi: 10.1007/s12029-011-9330-9.
The expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in sporadic colorectal carcinoma (CRC). EGFR inhibitors are approved for the treatment of refractory CRC. The aim of this study was to investigate the expression of EGFR and HER2 and downstream extracellular signal regulated kinase (ERK) and mitogen activated protein kinase (MAPK) in non-neoplastic colonic mucosa, adenomas and carcinomas from familial adenomatous polyposis coli (FAP) patients, exploring the expression along the adenoma-carcinoma sequence.
The expression of EGFR, HER2, phosphorylated MAPK/ERK kinase (pMEK) and phosphorylated ERK (pERK) proteins was studied by immunohistochemistry in samples of colonic non-neoplastic mucosa (n = 65), adenomas (n = 149) and adenocarcinomas (n = 16) from each of the 16 FAP patients.
For HER2, only weak cytoplasmic expression was seen in 8% of adenomas, 6% of carcinomas and 3% of the non-neoplastic mucosa. EGFR was expressed in non-neoplastic mucosa, adenomas and carcinomas with a statistically significant increase in expression in adenomas compared with non-neoplastic mucosa (p < 0.001). There was also a statistically significant increase in nuclear staining intensity for pERK (p < 0.001) and pMEK (p < 0.001) in adenomas compared to non-neoplastic mucosa.
This is the first study investigating the expression of these receptors in non-neoplastic mucosa, adenomas and carcinomas from FAP patients. HER2 is not upregulated in the tumours of FAP patients, while EGFR appears to be upregulated in most adenomas and carcinomas, with associated upregulation of pERK and pMEK. We conclude that EGFR and downstream members of its signalling pathway, but not HER2, may be potential therapeutic targets in FAP patients.
表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER2）的表达与散发性结直肠癌（CRC）的不良预后相关。EGFR抑制剂已被批准用于治疗难治性CRC。本研究的目的是调查家族性腺瘤性息肉病（FAP）患者的非肿瘤性结肠黏膜、腺瘤和癌组织中EGFR和HER2以及下游细胞外信号调节激酶（ERK）和丝裂原活化蛋白激酶（MAPK）的表达情况，探索沿腺瘤-癌序列的表达变化。
通过免疫组织化学研究16例FAP患者的结肠非肿瘤性黏膜样本（n = 65）、腺瘤样本（n = 149）和腺癌样本（n = 16）中EGFR、HER2、磷酸化MAPK/ERK激酶（pMEK）和磷酸化ERK（pERK）蛋白的表达。
对于HER2，仅在8%的腺瘤、6%的癌和3%的非肿瘤性黏膜中观察到弱细胞质表达。EGFR在非肿瘤性黏膜、腺瘤和癌中均有表达，与非肿瘤性黏膜相比，腺瘤中的表达有统计学显著增加（p < 0.001）。与非肿瘤性黏膜相比，腺瘤中pERK（（p < 0.001）和pMEK（p < 0.001）的核染色强度也有统计学显著增加。
这是第一项研究FAP患者非肿瘤性黏膜、腺瘤和癌中这些受体表达的研究。HER2在FAP患者的肿瘤中未上调，而EGFR在大多数腺瘤和癌中似乎上调，同时伴有pERK和pMEK的上调。我们得出结论，EGFR及其信号通路的下游成员而非HER2可能是FAP患者的潜在治疗靶点。
