Department of Pathology, School of Basic Medical Science, Wuhan University, 185 Donghu Road, Wuchang District, 430071, Wuhan, China.
Int J Colorectal Dis. 2013 Oct;28(10):1329-35. doi: 10.1007/s00384-013-1689-6. Epub 2013 May 4.
Molecular testing for epidermal growth factor receptor (EGFR) mutations has recently become a standard practice for the management of patients with non-squamous none small cell lung cancer. Primary small intestine adenocarcinoma (SIA) is an uncommon malignancy, and EGFR mutation in the cancer has not been well characterized due to its rarity.
A micro-tissue array with 53 SIAs and 24 surgically resected primary non-ampullary SIAs were studied. EGFR mutations were analyzed by DNA sequencing in 24 cases with formalin-fixed paraffin-embedded blocks. All 77 cases were examined by immunohistochemistry (IHC) using antibodies specific for the EGFR E746-A750 deletion in exon 19 (DEL), L858R point mutation in exon 21 (L858R), and total EGFR. EGFR amplifications were detected by fluorescence in situ hybridization.
A positive reaction of DEL-specific, L858R-specific, and total EGFR antibodies was detected in seven (9.1%), 5 (6.5%) and 35 (45.5%) of 77 SIAs by IHC, respectively. Positive reaction of the three antibodies was not significantly correlated with patient's age, gender, differentiation, and stage. EGFR gene amplification was assayed in 77 SIAs in micro-tissue array. Of 24 SIA samples that had DNA sequencing, two (8.3%) harbored exon 19 deletion and one (4.2%) harbored L858R point mutation. Only one case with EGFR amplification and two cases with polysomy were shown.
Our findings suggested that mutations and amplification in EGFR genes are minor events, and most of SIAs may be unsuitable to EGFR-TKIs treatment.
表皮生长因子受体（EGFR）突变的分子检测最近已成为非鳞状非小细胞肺癌患者管理的标准实践。原发性小肠腺癌（SIA）是一种罕见的恶性肿瘤，由于其罕见性，癌症中的 EGFR 突变尚未得到很好的描述。
研究了 53 例 SIA 和 24 例手术切除的原发性非壶腹 SIA 的微组织阵列。对 24 例福尔马林固定石蜡包埋块进行 DNA 测序分析 EGFR 突变。所有 77 例均通过针对 EGFR 外显子 19 缺失（DEL）、外显子 21 点突变（L858R）和总 EGFR 的 EGFR E746-A750 的抗体进行免疫组织化学（IHC）检测。通过荧光原位杂交检测 EGFR 扩增。
通过 IHC，DEL 特异性、L858R 特异性和总 EGFR 抗体的阳性反应分别在 77 例 SIA 中的 7 例（9.1%）、5 例（6.5%）和 35 例（45.5%）中检测到。三种抗体的阳性反应与患者的年龄、性别、分化和分期无显著相关性。在微组织阵列中对 77 例 SIA 进行了 EGFR 基因扩增检测。在 24 例有 DNA 测序的 SIA 样本中，2 例（8.3%）存在外显子 19 缺失，1 例（4.2%）存在 L858R 点突变。仅显示 1 例 EGFR 扩增和 2 例多倍体。
我们的研究结果表明，EGFR 基因的突变和扩增是少见事件，大多数 SIA 可能不适合 EGFR-TKIs 治疗。
