Lei Yuanyuan, Sun Nan, Zhang Guochao, Liu Chengming, Lu Zhiliang, Huang Jianbing, Zhang Chaoqi, Zang Ruochuan, Che Yun, Mao Shuangshuang, Fang Lingling, Wang Xinfeng, Zheng Sufei, He Jie
National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical college, Beijing, China.
Clin Transl Med. 2020 Jul;10(3):e128. doi: 10.1002/ctm2.128. Epub 2020 Jul 13.
Many tumor-derived endothelial cells (TECs) are shed into the blood and turn into circulating TECs (CTECs). Rare circulating non-hematologic aneuploid cells contain CTCs and CTECs, which are biologically and functionally different from each other. CD31 is one of the most representative endothelial cell (EC) markers, yet CD31 alone is not sufficient to detect malignant CTECs due to the existence of abundant normal ECs in circulation. Aneuploidy of chromosome 8 (CEP8) is an important criterion for the identification of malignant cells. Combined in situ phenotypic and karyotypic characterization, which includes an examination of both protein expression and aneuploid chromosomes, has demonstrated its unique advantage for both effective distinguishing and comprehensive detection of CTCs and CTECs.
A total of 98 subjects were recruited in the current study, including healthy donors and patients with benign disease and early-stage non-small-cell lung cancer (NSCLC). SE-iFISH was performed to quantitatively analyze diverse subtypes of aneuploid CD31 CTECs and CD31 CTCs classified upon the ploidy of chromosome 8 and tumor marker expression in the specimens collected from the recruited subjects.
CD31 CTCs primarily consist of triploid CTCs with a small cell size (≤5 µm) and large hyperploid CTCs (≥ pentaploid), whereas CD31 CTECs are mainly comprised of large hyperploid cells. Enumeration of the total numbers of both CTCs and CTECs might help identify malignant nodules with a high sensitivity, whereas quantification of tetraploid CTCs and CTECs specifically exhibited a high specificity for the identification of malignant nodules.
Combined detection of the specific subtypes of aneuploid CD31 CTECs and CD31 CTCs may help to effectively identify malignant nodules with a higher sensitivity and specificity in early stage NSCLC patients.
许多肿瘤来源的内皮细胞（TECs）会脱落进入血液并转变为循环肿瘤内皮细胞（CTECs）。罕见的循环非血液学非整倍体细胞包含循环肿瘤细胞（CTCs）和CTECs，它们在生物学和功能上彼此不同。CD31是最具代表性的内皮细胞（EC）标志物之一，但由于循环中存在大量正常ECs，仅靠CD31不足以检测出恶性CTECs。8号染色体非整倍体（CEP8）是鉴定恶性细胞的重要标准。原位表型和核型联合鉴定，包括蛋白质表达和非整倍体染色体检查，已证明其在有效区分和全面检测CTCs和CTECs方面具有独特优势。
本研究共招募了98名受试者，包括健康供体、良性疾病患者和早期非小细胞肺癌（NSCLC）患者。采用SE-iFISH对招募受试者采集的标本中根据8号染色体倍性和肿瘤标志物表达分类的非整倍体CD31 CTECs和CD31 CTCs的不同亚型进行定量分析。
CD31 CTCs主要由细胞体积小（≤5 µm）的三倍体CTCs和大超倍体CTCs（≥五倍体）组成，而CD31 CTECs主要由大超倍体细胞组成。CTCs和CTECs总数的计数可能有助于高灵敏度地识别恶性结节，而四倍体CTCs和CTECs的定量分析对恶性结节的识别具有高特异性。
联合检测非整倍体CD31 CTECs和CD31 CTCs的特定亚型可能有助于在早期NSCLC患者中以更高的灵敏度和特异性有效识别恶性结节。
