K-ras-2 topographic genotyping of pancreatic adenocarcinoma.
K-ras-2 topographic genotyping of pancreatic adenocarcinoma.
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DOI：
10.1001/archsurg.1994.01420280037005
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发表时间：
1994-04
影响因子：
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通讯作者：
S. Finkelstein;R. Przygodzki;V. Pricolo;R. Sayegh;A. Bakker;P. Swalsky;G. Keller
中科院分区：
文献类型：
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作者：
S. Finkelstein;R. Przygodzki;V. Pricolo;R. Sayegh;A. Bakker;P. Swalsky;G. Keller
目的探讨胰腺癌组织中K-ras-2点突变基因型的频率分布，并评价K-ras-2基因分型作为预测胰腺癌局部病变和长期生存的有效性。设计采用聚合酶链反应产物和直接测序技术，对福尔马林固定、石蜡包埋的大型和活检组织标本以及细胞液进行局部基因分型，并结合临床病理学和统计学分析。设置三级保健医疗中心与分子诊断病理实验室。1988年至1993年在普罗维登斯的罗得岛医院治疗的患者，获得55例原发性和56例转移性胰腺癌标本。结果发现每个原发性胰腺癌都含有八种特定基因型中的一种，这些基因型在该个体肿瘤的所有转移性沉积物中保持。诊断时局限于胰床的原发性腺癌主要为正常基因型（56% [14/25]）。进展为远处血源性转移的胰腺腺癌几乎全部发生突变（88% [7/8]; P < .005）。接受胰腺切除术（维普莱手术）且K-ras-2基因型正常的患者（58% [11/19]）的生存期（21.3个月）明显长于类似的突变肿瘤患者（8.2个月）。结论：研究结果支持K-ras-2地形基因分型识别潜在惰性疾病的可行性，并建议在胰腺癌术前评估中发挥潜在有用的作用。
OBJECTIVE To determine the frequency distribution of K-ras-2 point mutation genotypes in pancreatic adenocarcinoma and to evaluate the effectiveness of K-ras-2 genotyping as a means to predict localized disease and potential long-term survival. DESIGN Topographic genotyping from archival formalin-fixed, paraffin-embedded large- and biopsy-sized tissue specimens as well as cytologic fluid using polymerase chain reaction products and direct sequencing together with clinicopathologic and statistical analysis. SETTING Tertiary care medical center with molecular diagnostics pathology laboratory. PATIENTS Patients treated between 1988 and 1993 at Rhode Island Hospital, Providence, yielding 55 primary and 56 metastatic specimens of pancreatic adenocarcinoma. RESULTS Each primary pancreatic adenocarcinoma was found to contain one of eight specific genotypes that was maintained in all metastatic deposits of that individual tumor. Primary adenocarcinomas confined to the pancreatic bed at diagnosis were predominantly of a normal genotype (56% [14/25]). Pancreatic adenocarcinomas progressing to distant hematogenous metastasis were almost exclusively mutated (88% [7/8]; P < .005). Patients undergoing pancreatic resection (Whipple's operation) and having a normal K-ras-2-genotype (58% [11/19]) had a significantly longer survival (21.3 months) than similar patients with mutated tumors (8.2 months). CONCLUSIONS The findings support the feasibility of K-ras-2 topographic genotyping to identify potentially indolent disease and suggest a potentially useful role in the preoperative evaluation of pancreatic adenocarcinoma.