Objective: The new concept of cancer stem cells has implications in terms of possible application for novel diagnostic and therapeutic procedures. Recently, the CD133 molecule was reported as a marker of cancer stem-like cells in colorectal cancer (CRC). In this study, we examined the prognostic value of free cancer cells in peritoneal washings from CRC patients after curative resection using multiple molecular markers, including cancer stem-like cells. Methods: A total of 170 CRC patients who had undergone curative surgery were studied. Peritoneal washings of the Douglas cavity were collected and used for cytology and molecular diagnosis. Real-time RT-PCR for carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and CD133 mRNA was performed to detect free cancer cells. Results: Molecular detection of CEA, CK20 and/or CD133 (CEA/CK20/CD133) mRNA of the peritoneal washings showed a significant correlation with lymph node metastasis and the tumor stage. The overall survival (OS) rates and peritoneal recurrence-free survival (PFS) rates in CEA/CK20/CD133 mRNA-positive patients were significantly lower than those of marker gene-negative patients. CD133/CEA/CK20 mRNAs in peritoneal washings were independent prognostic factors for OS and PFS. Conclusion: Molecular detection of free cancer cells using multimarkers, including cancer stem-like cells in peritoneal washings of post-curative surgery CRC patients, are useful in prognosis prediction.

Weitz J, Koch M, Debus J, Hohler T, Galle PR, Bucler MW: Colorectal cancer. Lancet 2005;465:153–165.
Cass AW, Million RR, Pfaff WW: Pattern of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Cancer 1976;37:2861–2865.
Jayne DG, Fook S, Loi C, Seow-Choen: Peritoneal carcinomatosis from colorectal cancer. Br J Surg 2002;89:1545–1550.
Murphy PD, Wadhera V, Griffin SM, Burgess P, Farrell D, Taylor I, Hair T, Clague MB, Griffith CDM: Free peritoneal tumor cell identification in patients with gastric and colorectal cancer. J R Coll Surg Edinb 1993;38:28–32.
Wind P, Norklinger B, Roger V, Kahlil A, Guin E, Parc R: Long-term prognostic value of positive peritoneal washing in colon cancer. Scand J Gastoenterol 1999;34:606–610.
Kanellos I, Demetriades H, Zintzaras E, Mandrail A, Mantzoros I, Besis D: Incidence and prognosti value of positive peritoneal cytology in colorectal cancer. Dis Colon Rectum 2003;46:535–539.
Gozalan U, Yasti AC, Yuksek YN, Reis E, Kama NA: Peritoneal cytology in colorectal cancer and prognostic value. Am J Surg 2007;193:672–675.
Lenon A, Mulcapy HE, Hyland JM, et al: Peritoneal involvement in stage II colon cancer. Am J Clin Pathol 2003;119:108–113.
Yamamoto S, Akasu T, Fujita S, Moriya Y:Long-term prognostic value of conventional peritoneal cytology after curative resection for colorectal carcinoma. Jpn J Clin Oncol 2003;33:33–37.
Nakanishi H, Kodera Y, Yamamura Y, Ito S, Kato T, Ezaki T, Tatematsu M: Rapid quantitative detection of carcinoembryonic antigen-expressing free tumor cells in the peritoneal cavity of gastric cancer patients with real-time RT-PCR on the lightcycler. Int J Cancer 2000;89:411–417.
Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Simizu Y, Hirai T, Yasui K, Kato T, Tatematsu M: Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction. Ann Surg 2002;235:499–506.
Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–111.
Pardal R, Clarke MF, Morrison SJ: Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003;3:895–902.
Wulf GG, Wang RY, Kuehne I, Weidner D, Marini F, Brenner MK, Andreeff M, Goodell MA: A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia. Blood 2001;98:1166–1173.
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE: A cell initiating human acute myeloid leukemia after transplantation into SCID mice. Nature 1994;367:645–648.
O’Brien CA, Pollett A, Gallinger S, Dick JE: A human colon cancer cell capable of initiating tumor growth in immunodeficient mice. Nature 2007;445:106–110.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, Maria RD: Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445:111–115.
Hayama T, Iinuma H, Watanabe T: Rapid genetic diagnosis with transcription-reverse transription concerted reaction system for peritoneal recurrence and survival in colorectal cancer patients. Oncol Rep 2007;18:779–784.
Ieta K, Tanaka F, Haraguchi N, Kita Y, Sakashita H, Mimori K, Matsumoto T, Inoue H, Kuwano H, Mori M: Biologial and genetic characteristics of tumor-initiating cells in colon cancer. Ann Surg Oncol 2008;15:638–648.
Shmelkov SV, St Clair R, Lyden D, Rafii S: AC133/CD133/prominin-1. Int J Biochem Cell Biol 2005;37:715–719.
Bhatia M: AC133 expression in human stem cells. Leukemia 2001;15:1685–1688.
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB: Identification of a cancer stem cell in human brain tumors. Cancer Res 2003;63:5821–5828.
Yin S, Li J, Hu C, Chen X, Yao M, Yan M, Jiang G, Ge C, Xie H, Wan D, Yang S, Zheng S, Gu J: CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity. Int J Cancer 2007;120:1444–1450.
Guller U, Zajac P, Schnider A, Bosch B, Vorburger S, Zuber M, Spagnoli GC, Oertli DC, Maurer R, Metzger U, Harder F, Heberer M, Marti R: Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer. Ann Surg 2002;236:768–776.
Lloyd JM, McIver CM, Sephenson SA, Hewett PJ, Rieger N, Hardinghm JE: Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid of malignant cells. Clin Cancer Res 2006;12:417–423.
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