Detection of disseminated tumor cells in peripheral blood of colorectal cancer patients

Abstract

All cancer staging systems seek to identify clinical and pathological features that can predict outcome or guide therapy. In particular, a non‐invasive method for the early detection of disseminating disease would be of great interest. We investigated the use of cytokeratin genes expression to detect blood metastases from colorectal tumors. Epithelial tumor cells were isolated from whole blood using the monoclonal antibody (MAb) BerEP4 and magnetic beads, and detected by reverse transcription‐polymerase chain reaction using oligonucleotides derived from the cDNA sequences of cytokeratins 8, 19 and 20. The sensitivity of this assay was determined by spiking SW620 colon carcinoma cells in normal blood. Using cytokeratin 19 expression we were able to detect 1 epithelial tumor cell in 1 ml of whole blood. The clinical applicability of this technique was explored by evaluating patients with a colorectal carcinoma. Epithelial cells were detected in the blood of 12 out of 23 patients, 2 (20%) of 10 with Astler‐Coller stage A or B, and 10 (77%) of 13 with stage C or D cancer. In conclusion, this test is a non‐invasive, sensitive, and specific assay for detecting circulating epithelial cells in blood. It may be useful for the early diagnosis of disseminating disease, to determine whether the presence of micrometastatic cells at the time of surgery is correlated with an early relapse and for monitoring adjuvant therapeutic trials. Int. J. Cancer 74:540–544, 1997. © 1997 Wiley‐Liss, Inc.

Detection of colonic cells in peripheral blood of colorectal cancer patients by means of reverse transcriptase and polymerase chain reaction

“…Cytokeratins, a multigene family of proteins with differentiationassociated patterns of expression (Moll et al, 1982), have also been used to characterize neoplastic cells of epithelial origin in bone marrow (Lindemann et al 1992) and peripheral blood (Denis et al, 1997;Nakamori et al, 1997;Soeth et al, 1997). However, most of them are found in samples of healthy subjects, thus limiting their suitability as targets (Burchill et al, 1995).…”

“…it has been possible to identify circulatinc cancer cells in patients xxith different neoplasms (Smith et al 1991: Moreno et al 1992: Tada et al 1993: Hillaire et al 1994. including colorectal cancer (Hardingham et al 1995: Jonas et al 1996: Denis et al 1997 Nakamori et al. : Wonc et al 1997.…”

“…Catalonia. Spain the lack of an extensive control group (Denis et al 1997: Nakamonr et al 1997: Wong et al 1997 or the inclusion of onlx patients wxith colorectal lixer metastases (Jonas et al 1996) preclude an appropriated assessment of both accuracv of this method and the relationship betx-een presence of circulating malignant cells and tumour stage.…”

Regional anesthesia and prostate cancer recurrence

“…Furthermore, many patients already harbour micrometastases and scattered tumour cells at the time of surgery. [1][2][3] Whether residual cancer cells progress to clinical metastases depends largely on the balance between antimetastatic immune activity and the tumour's ability to seed, proliferate, and attract new blood vessels. [4][5][6] At least three perioperative factors shift the balance toward progression of minimal residual disease:…”

Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients

“…After primary resection surgery minimal residual cancer cells (MRCC) are the actual targets for chemotherapeutic drugs. Until now several attempts have been made to detect or isolate disseminated tumour cells from peripheral blood or bone marrow (Nawroz et al, 1996;Denis et al, 1997;Brandt et al, 1998;Leitzel et al, 1998;Naume et al, 1998;Soria et al, 1999). In nearly all analytical approaches, RT-PCR analyses were used to detect micrometastatic, disseminated cancer cells.…”