Owonikoko Taofeek, Rees Martin, Gabbert Helmut E, Sarbia Mario
Institute of Pathology, Heinrich-Heine-University, Düsseldorf, Germany.
Am J Clin Pathol. 2002 Apr;117(4):558-66. doi: 10.1309/6XY8-FMM5-VVCJ-T3N0.
In 10 cases of Barrett adenocarcinoma, samples from 8 tumor areas (including superficial and deep from peripheral and central areas) and a regional lymph node metastasis were studied for amplification of c-myc, c-erbB-2, and EGFR. We analyzed loss of heterozygosity (LOH) at 3 loci (APC, MCC, and RB) and 2 anonymous microsatellite markers (D4S1652 and D18S474). We detected c-myc in variable fractions of tissue samples from 3 of 9 tumors; EGFR was amplified in 2 specimens from 1 tumor. One tumor demonstrated amplification of c-erbB-2 in all areas. LOH at the D4S1652, MCC, RB, APC, and D18S474 loci was found in 75% (3/4), 57% (4/7), 50% (4/8), 11% (1/9), and 0% (0/10) of informative cases, respectively. LOH generally was restricted to variable subpopulations of tumor cells within individual tumors. There was no obvious association of certain genetic alterations with topographically distinct tumor regions; however, superficial areas showed more frequent genetic alterations than areas from the deeply invading front. More aberrations were detected in the periphery than in the center. Barrett adenocarcinoma is characterized by marked intratumoral genetic heterogeneity, which must be considered when evaluating genetic alterations as indicators of response to therapy and prognosis.
在10例巴雷特腺癌病例中，对8个肿瘤区域（包括外周和中央区域的浅表和深部）以及1个区域淋巴结转移灶的样本进行了c-myc、c-erbB-2和表皮生长因子受体（EGFR）扩增研究。我们分析了3个位点（腺瘤性息肉病基因（APC）、错配修复基因（MCC）和视网膜母细胞瘤基因（RB））以及2个匿名微卫星标记（D4S1652和D18S474）的杂合性缺失（LOH）情况。我们在9个肿瘤中的3个肿瘤的不同组织样本中检测到了c-myc；在1个肿瘤的2个样本中检测到EGFR扩增。1个肿瘤在所有区域均显示c-erbB-2扩增。在信息充足的病例中，D4S1652、MCC、RB、APC和D18S474位点的LOH发生率分别为75%（3/4）、57%（4/7）、50%（4/8）、11%（1/9）和0%（0/10）。LOH通常局限于单个肿瘤内不同的肿瘤细胞亚群。某些基因改变与地形学上不同的肿瘤区域之间没有明显关联；然而，浅表区域的基因改变比深部浸润前沿区域更频繁。在外周检测到的畸变比中央更多。巴雷特腺癌的特征是肿瘤内存在明显的基因异质性，在将基因改变作为治疗反应和预后指标进行评估时，必须考虑这一点。
