Timme-Bronsert S, Bronsert P, Werner M, Kulemann B, Höppner J
Institut für Klinische Pathologie, Universitätsklinikum Freiburg, Breisacher Straße 115A, 79106, Freiburg, Deutschland.
Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg, Deutschland.
Pathologe. 2018 Dec;39(Suppl 2):311-314. doi: 10.1007/s00292-018-0550-7.
Pancreatic ductal adenocarcinoma (PDAC) is a disease with a poor prognosis. PDAC shows characteristic mutations within codon 12/13. Circulating tumor cells (CTC) detected in blood samples of patients with cancer are hypothesized as the means of systemic tumor spread. But less is known about morphological/molecular characteristics or the pathophysiological meaning of PDAC CTC.
The aim of the study was a cytomorphological and genetic analysis of CTC from patients with PDAC followed by the correlation of the results with those of the corresponding tumor in the pancreas.
Blood samples of 58 patients with PDAC and 10 "normal" control donors were processed through a size-based CTC isolation. KRAS-mutation analyses were performed for CTC and the primary tumor and the results were compared. Furthermore, their potential as a prognostic marker was evaluated.
In patients with different UICC stages CTC were detected, but not in normal control patients. There was a trend for a worse median overall survival (OS) for patients with >3 CTC/ml. Patients with a KRAS mutation showed a trend for a better median OS compared to those with other KRAS mutations (10 months) or even without KRAS mutation. Fifty-eight percent of the patients presented concordant KRAS mutations in the primary tumor and corresponding CTC, while 42% were discordant. The median OS for both groups was similar.
Detection and characterization of CTC (for example by KRAS mutation analysis) may be useful for prognosis. Furthermore, it expands our knowledge of tumor biology and may detect possible tumor heterogeneity regarding the mutation profile of some cancer types.
胰腺导管腺癌(PDAC)是一种预后较差的疾病。PDAC在密码子12/13内显示出特征性突变。癌症患者血样中检测到的循环肿瘤细胞(CTC)被认为是肿瘤全身扩散的途径。但关于PDAC CTC的形态学/分子特征或病理生理学意义知之甚少。
本研究旨在对PDAC患者的CTC进行细胞形态学和遗传学分析,然后将结果与胰腺相应肿瘤的结果进行相关性分析。
对58例PDAC患者和10例“正常”对照供体的血样进行基于大小排阻的CTC分离。对CTC和原发肿瘤进行KRAS突变分析,并比较结果。此外,评估它们作为预后标志物的潜力。
在不同UICC分期的患者中检测到CTC,但在正常对照患者中未检测到。CTC>3/ml的患者中位总生存期(OS)有变差的趋势。与其他KRAS突变(10个月)甚至无KRAS突变的患者相比,KRAS突变患者的中位OS有变好的趋势。58%的患者在原发肿瘤和相应的CTC中存在一致的KRAS突变,而42%不一致。两组的中位OS相似。
CTC的检测和特征分析(例如通过KRAS突变分析)可能有助于预后评估。此外,它扩展了我们对肿瘤生物学的认识,并可能检测到某些癌症类型在突变谱方面可能存在的肿瘤异质性。