title: Usefulness and clinical significance of quantitative real-time RT-PCR to detect isolated tumor cells in the peripheral blood and tumor drainage blood of patients with colorectal cancer.
abstract: The clinical significance of isolated tumor cells (ITC) circulating in the blood of patients with colorectal cancer is unclear. In this study, we investigated the relationship between the presence of ITC that express carcinoembryonic antigen (CEA) and/or cytokeratin 20 (CK20) transcripts in the blood and the clinicopathological findings and prognosis using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. We studied peripheral blood and tumor drainage blood from 167 patients with colorectal cancer. Quantitative real-time RT-PCR assay was able to detect one tumor cell in 3x10(6) peripheral blood mononuclear cells. Applying a cut-off value, CEA and/or CK20 (CEA/CK20) were detected in 10.2% (17/167) of the patients' preoperative peripheral blood samples and 34.1% (57/167) of the patients' tumor drainage blood samples. In the relationship between the CEA/CK20 of the blood and the clinicopathological factors, a significant correlation was demonstrated between the positivity of marker genes and the depth of invasion, venous invasion, lymph node metastasis, liver metastasis or stage. The disease-free and overall survival of patients with CEA/CK20-positive peripheral or tumor drainage blood was significantly shorter than that of marker gene-negative patients. CEA/CK20 transcripts in tumor drainage blood were independent factors for prognosis in disease-free survival and overall survival. These results suggest that detecting CEA/CK20 mRNA in tumor drainage blood by real-time RT-PCR has prognostic value in patients with colorectal cancer. Large scale and long-term clinical studies are needed to confirm the prognostic value of genetically detecting ITC in the peripheral blood.
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-0003, Japan. iinuma@med.teikyo-u.ac.jp
authors.forename: Hisae
authors.initials: H
authors.lastname: Iinuma
authors.forename: Kota
authors.initials: K
authors.lastname: Okinaga
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egami
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Naoko
authors.initials: N
authors.lastname: Hayashi
authors.forename: Koujiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Miki
authors.initials: M
authors.lastname: Adachi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sasako
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood / Q000473:pathology*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D053554:Keratin-20 / Q000097:blood / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053554:Keratin-20; D012333:RNA, Messenger