Detecting and phenotyping of aneuploid circulating tumor cells in patients with various malignancies

Cancer Biol Ther. 2019;20(4):546-551. doi: 10.1080/15384047.2018.1538000. Epub 2018 Dec 20.

Abstract

Circulating tumor cells (CTCs) have been exclusively studied and served to assess the clinical outcomes of treatments and progression of cancer. Most CTC data have mainly been derived from distinct cohorts or selected tumor types. In the present study, a total of 594 blood samples from 479 cases with 19 different carcinomas and 30 healthy samples were collected and analyzed by Subtraction enrichment method combined with immunostaining-fluorescence in situ hybridization (iFISH). Non-hematopoietic cells with aneuploid chromosome 8 (more than 2 copies) were regarded as positive CTCs. The results showed that none of CTCs was found in all 30 healthy samples. The overall positive rate of CTCs was 89.0% in diagnosed cancer patients (ranging from 75.0% to 100.0%). Average number of 11, 5, 8 and 4 CTCs per 7.5 mL was observed in lung cancer, liver cancer, renal cancer and colorectal cancer, respectively. Among 19 different carcinomas, the total number of CTCs, tetraploid chromosome 8, polyploid chromosome 8, CTM (Circulating tumor microemboli) and large CTCs in patients with stage Ⅲ and Ⅳ were statistically higher than patients with stage Ⅰ and Ⅱ (P < 0.05). Furthermore, EpCAM expression was more frequently found in most CTCs than vimentin expression, confirming that these CTCs were of epithelial origin. In addition, small and large CTCs were also classified, and the expression of vimentin was mostly observed in small CTCs and CTM. Our results revealed that there are higher numbers of CTCs, tetraploid, polyploid and large CTCs in patients with stage Ⅲ and Ⅳ, indicating that the quantification of chromosome ploidy performed by SE-iFISH for CTCs might be a useful tool to predict and evaluate therapeutic efficacy as well as to monitoring disease progression.

Keywords: CTCs; Circulating tumor cells; EpCAM; Vimentin; iFISH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Case-Control Studies
  • Cohort Studies
  • Epithelial Cell Adhesion Molecule / metabolism*
  • Follow-Up Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis
  • Vimentin / metabolism*

Substances

  • Biomarkers, Tumor
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • VIM protein, human
  • Vimentin

Grants and funding

This work was supported by the National Key Research and Development Program (2017YFC0909800), the National Science Fund Projects (8167110226, 81703047), the Study on the application system of tumor intelligence precision medical treatment based on large health data of Shanghai Informatization Development Special project (201602037) and the Capacity Building Project of Shanghai Engineering Research Center (16DZ2281000).