Kulemann Birte, Pitman Martha B, Liss Andrew S, Valsangkar Nakul, Fernández-Del Castillo Carlos, Lillemoe Keith D, Hoeppner Jens, Mino-Kenudson Mari, Warshaw Andrew L, Thayer Sarah P
From the *Department of Surgery and †Andrew L. Warshaw Institute for Pancreatic Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA; ‡Department of Surgery, University Hospital Freiburg, Freiburg, Germany; §Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and ║Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.
Pancreas. 2015 May;44(4):547-50. doi: 10.1097/MPA.0000000000000324.
Isolation of circulating tumor cells (CTCs) holds the promise of diagnosing and molecular profiling cancers from a blood sample. Here, we test a simple new low-cost filtration device for CTC isolation in patients with pancreatic ductal adenocarcinoma (PDAC).
Peripheral blood samples drawn from healthy donors and PDAC patients were filtered using ScreenCell devices, designed to capture CTCs for cytologic and molecular analysis. Giemsa-stained specimens were evaluated by a pancreatic cytopathologist blinded to the histological diagnosis. Circulating tumor cell DNA was subjected to KRAS mutational analysis.
Spiking experiments demonstrated a CTC capture efficiency as low as 2 cells/mL of blood. Circulating tumor cells were identified by either malignant cytology or presence of KRAS mutation in 73% of 11 patients (P = 0.001). Circulating tumor cells were identified in 3 of 4 patients with early (≤American Joint Committee on Cancer stage IIB) and in 5 of 7 patients with advanced (≥ American Joint Committee on Cancer stage III) PDAC. No CTCs were detected in blood from 9 health donors.
Circulating tumor cells can be found in most patients with PDAC of any stage, whether localized, locally advanced, or metastatic. The ability to capture, cytologically identify, and genetically analyze CTCs suggests a possible tool for the diagnosis and characterization of genetic alterations of PDAC.
分离循环肿瘤细胞（CTC）有望从血液样本中诊断癌症并进行分子分析。在此，我们测试一种简单、新型且低成本的过滤装置，用于在胰腺导管腺癌（PDAC）患者中分离CTC。
使用ScreenCell装置对从健康供体和PDAC患者采集的外周血样本进行过滤，该装置旨在捕获CTC以进行细胞学和分子分析。由对组织学诊断不知情的胰腺细胞病理学家评估吉姆萨染色的标本。对循环肿瘤细胞DNA进行KRAS突变分析。
加标实验表明，CTC捕获效率低至每毫升血液2个细胞。在11例患者中的73%（P = 0.001）通过恶性细胞学或KRAS突变的存在鉴定出循环肿瘤细胞。在4例早期（≤美国癌症联合委员会IIB期）PDAC患者中的3例以及7例晚期（≥美国癌症联合委员会III期）PDAC患者中的5例检测到循环肿瘤细胞。在9名健康供体的血液中未检测到CTC。
在任何阶段的大多数PDAC患者中均可发现循环肿瘤细胞，无论其为局限性、局部进展性或转移性。捕获、细胞学鉴定和基因分析CTC的能力提示其可能成为诊断和表征PDAC基因改变的一种工具。
