Finkelstein S D, Przygodzki R, Pricolo V E, Sayegh R, Bakker A, Swalsky P A, Keller G
Department of Pathology, Prebyterian University Hospital, University of Pittsburgh, Pa.
Arch Surg. 1994 Apr;129(4):367-72; discussion 372-3. doi: 10.1001/archsurg.1994.01420280037005.
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.
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.
Tertiary care medical center with molecular diagnostics pathology laboratory.
Patients treated between 1988 and 1993 at Rhode Island Hospital, Providence, yielding 55 primary and 56 metastatic specimens of pancreatic adenocarcinoma.
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).
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.
确定胰腺腺癌中K-ras-2点突变基因型的频率分布，并评估K-ras-2基因分型作为预测局限性疾病和潜在长期生存手段的有效性。
使用聚合酶链反应产物和直接测序，对存档的福尔马林固定、石蜡包埋的大组织和活检组织标本以及细胞液进行地形基因分型，并进行临床病理和统计分析。
设有分子诊断病理实验室的三级医疗中心。
1988年至1993年在普罗维登斯罗德岛医院接受治疗的患者，共获得55例胰腺腺癌原发标本和56例转移标本。
发现每例胰腺腺癌原发灶均包含8种特定基因型中的一种，且该基因型在该个体肿瘤的所有转移灶中均保持一致。诊断时局限于胰腺床的原发性腺癌主要为正常基因型（56%[14/25]）。进展为远处血行转移的胰腺腺癌几乎均发生了突变（88%[7/8]；P<.005）。接受胰腺切除术（惠普尔手术）且K-ras-2基因型正常的患者（58%[11/19]）的生存期（21.3个月）明显长于肿瘤发生突变的类似患者（8.2个月）。
这些发现支持了K-ras-2地形基因分型用于识别潜在惰性疾病的可行性，并提示其在胰腺腺癌术前评估中可能具有有用的作用。
