The prognostic value of circulating tumor cells lacking cytokeratins in metastatic breast cancer patients. 2013

Lina Zhao, and Pengfei Li, and Fude Li, and Yongkun Yang, and Na Liu, and Li Cai
Department of Medicine, the Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

OBJECTIVE In this study, we detected epithelial circulating tumor cells (CTCs) that expressed cytokeratins and potential circulating tumor cells (pCTCs) that had lost expression of cytokeratins in metastatic breast cancer (MBC) patients. The aim of the study was to evaluate the prognostic significance of these two kinds of CTCs in MBC patients. METHODS We detected CTCs and pCTCs from 66 MBC patients using MACS immunomagnetic enrichment technology combined with immunocytochemistry (ICC). A cutoff score of 5 CTCs (or pCTCs) was set as a benchmark for prognosis in patients. Progression free survival (PFS) was calculated and analyzed during the following 24 months. RESULTS We evaluated the sensitivity of this method and recovery rates of the CTCs by spiking experiments. The loss number of tumor cells by our method was 0-15. The population with fewer than 5 CTCs showed significantly higher PFS than the group with 5 or more CTCs. The difference in PFS between the patients with 5 or more pCTCs and those with fewer than 5 pCTCs was statistically significant. The presence of these pCTCs more accurately predicted poor prognosis than the CTCs that express cytokeratins. CONCLUSIONS There is a subset of CTCs that lose epithelial markers such as pCTCs. Due to the heterogeneity of the expression of epithelial antigens in CTCs, different subtypes of CTCs exist. Independently of CTCs, the groups of patients with pCTCs had poorer prognoses.

UI MeSH Term Description Entries
D007633 Keratins A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION. Cytokeratin,Keratin Associated Protein,Keratin,Keratin-Associated Proteins,alpha-Keratin,Associated Protein, Keratin,Keratin Associated Proteins,Protein, Keratin Associated,alpha Keratin
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009360 Neoplastic Cells, Circulating Exfoliate neoplastic cells circulating in the blood and associated with metastasizing tumors. Circulating Neoplastic Cells,Embolic Tumor Cells,Embolism, Tumor,Neoplasm Circulating Cells,Tumor Cells, Embolic,Cells, Neoplasm Circulating,Circulating Cells, Neoplasm,Circulating Tumor Cells,Cell, Circulating Neoplastic,Cell, Circulating Tumor,Cell, Embolic Tumor,Cell, Neoplasm Circulating,Cells, Circulating Neoplastic,Cells, Circulating Tumor,Cells, Embolic Tumor,Circulating Neoplastic Cell,Circulating Tumor Cell,Embolic Tumor Cell,Embolisms, Tumor,Neoplasm Circulating Cell,Neoplastic Cell, Circulating,Tumor Cell, Circulating,Tumor Cell, Embolic,Tumor Cells, Circulating,Tumor Embolism,Tumor Embolisms
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D009367 Neoplasm Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Cancer Staging,Staging, Neoplasm,Tumor Staging,TNM Classification,TNM Staging,TNM Staging System,Classification, TNM,Classifications, TNM,Staging System, TNM,Staging Systems, TNM,Staging, Cancer,Staging, TNM,Staging, Tumor,System, TNM Staging,Systems, TNM Staging,TNM Classifications,TNM Staging Systems
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults

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