Different molecular profiles characterize well-differentiated endocrine tumors and poorly differentiated endocrine carcinomas of the gastroenteropancreatic tract
Different molecular profiles characterize well-differentiated endocrine tumors and poorly differentiated endocrine carcinomas of the gastroenteropancreatic tract
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DOI：
10.1158/1078-0432.ccr-1068-3
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发表时间：
2004-02-01
影响因子：
11.5
通讯作者：
Capella, C
中科院分区：
文献类型：
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作者：
Furlan, D;Cerutti, R;Capella, C
目的：胃肠胰腺内分泌肿瘤(ETS)的分子发病机制目前尚不清楚。这项工作的目的是对38例胃肠胰脏ET的原发部位和形态功能特征进行分子表征，指出有用的诊断或预后分子标记。实验设计：24例分化良好的ETS或癌(WDET/Cs；应用分布于第1、3、5q、6、11、17、18号染色体上的38个微卫星标记，对11例胰腺癌、3例胃腺癌、10例肠道癌和14例低分化内分泌癌(I胰腺癌、6例胃腺癌、7例结直肠癌)和14例低分化内分泌癌进行了微等位基因分型。结果：除8例无功能性胰腺内分泌肿瘤和1例结直肠癌外，低分化内分泌癌的等位基因失衡(ALs)比例均显著高于WDET/Cs(P=0.012)。AI值与Ki-67增殖指数呈显著正相关(F=0.004)，与单纯WDET/Cs组(P=0.011)相关。生存分析显示低AT率与较长生存期呈正相关(P=0.01)。结论：内分泌肿瘤的恶性进展似乎与复杂的等位基因和染色体不稳定性有关。尽管目前尚无明确的恶性肿瘤分子标志物，但染色体的倍性状态和错乱程度似乎是最具预测意义的遗传因素。
Purpose: The molecular pathogenesis of gastroenteropancreatic endocrine tumors (ETs) is still largely unknown. The purpose of this work was a molecular characterization of 38 gastroenteropancreatic ETs with respect to the primary site and to the morphofunctional profile, pointing out useful diagnostic or prognostic molecular markers.Experimental Design: Twenty-four well-differentiated ETs or carcinomas (WDET/Cs; 11 pancreatic, 3 gastric, and 10 intestinal) and 14 poorly differentiated endocrine carcinomas (I pancreatic, 6 gastric, and 7 colorectal) were microallelotyped using 38 polymorphic microsatellite markers covering chromosomes 1, 3, 5q, 6, 11, 17, and 18.Results: Regardless of the primary site, a significantly higher percentage of allelic imbalances (Als) was observed,in poorly differentiated endocrine carcinomas than in WDET/Cs (P = 0.012), except for 3 of 8 nonfunctioning pancreatic endocrine tumors and 1 colorectal WDEC, exhibiting multiple Als on chromosomes 1, 3, 6, and 11. A strong positive correlation between AI percentage and Ki-67 proliferation index was detected considering both the whole series of ETs (F = 0.004) and the group of WDET/Cs alone (P = 0.011). The survival analysis showed a positive correlation between low percentage of At and longer survival (P = 0.01). No recurrent Als at specific chromosomal regions were identifiable with respect to the primary site.Conclusions: The malignant progression of endocrine tumors seems to be associated with complex allelotypes and chromosomal instability. Although no specific molecular markers of malignancy can be defined with certainty, the ploidy status and the degree of chromosomal derangements appear to be the most informative genetic factors with prognostic significance.