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Erschienen in: Annals of Surgical Oncology 8/2008

01.08.2008 | Gastrointestinal Oncology

Persistent Presence of Postoperative Circulating Tumor Cells is a Poor Prognostic Factor for Patients with Stage I–III Colorectal Cancer after Curative Resection

verfasst von: Yih-Huei Uen, MD, Chien-Yu Lu, MD, Hsiang-Lin Tsai, MD, Fang-Jung Yu, MD, Ming-Yii Huang, MD, Tian-Lu Cheng, PhD, Shiu-Ru Lin, PhD, Jaw-Yuan Wang, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 8/2008

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Abstract

Aim

To detect pre- and postoperative circulating tumor cells (CTCs) in stage I–III colorectal cancer (CRC) patients undergoing curative resection and so identify a subgroup of patients who are at high risk for relapse.

Methods

Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen mRNA were used to detect CTCs in 438 CRC patients underwent curative resection.

Results

Out of 438 patients, 80 CRC patients were classified to preoperative (−)/postoperative (−), 221 patients were preoperative (+)/postoperative (−), while 137 patients were preoperative (+)/postoperative (+). Univariately, postoperative relapse was significantly correlated with depth of invasion (P = 0.032), lymph node metastasis (P < 0.001), vascular invasion (P = 0.001), perineural invasion (P = 0.013), and persistent presence of CTCs (P < 0.001). Using a multivariate proportional hazards regression analysis, the presence of lymph node metastasis (P = 0.012; HR, 7.652; 95% CI: 4.162–14.827), vascular invasion (P = 0.033; HR, 4.360; 95% CI: 2.793–10.847), and the persistent presence of CTCs (P < 0.001; HR, 29.486; 95% CI: 10.281–87.792) were demonstrated to be independent predictors for postoperative relapse. Combination of these three independent predictors showed that patients with any one positive predictor had a hazard ratio of sevenfold to develop postoperative relapse (P < 0.001; HR, 7.064; 95% CI: 4.354–11.464). Furthermore, the persistent presence of CTCs was strongly correlated with poorer relapse-free survival rates (all P < 0.001).

Conclusion

The promising results of this study suggest that persistent presence of postoperative CTCs may be a crucial prognostic factor adjuvant to conventional tumor markers in CRC patients who have undergone curative resection. Identification of these high-risk patients of persistent CTCs positivity is important and thus could help to define patients for adjuvant therapy with this tumor entity.
Literatur
2.
Zurück zum Zitat Byers T, Levin B, Rothenberger D, et al. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. American Cancer Society Detection and Treatment Advisory Group on Colorectal Cancer. CA Cancer J Clin 1997; 47:154–60PubMedCrossRef Byers T, Levin B, Rothenberger D, et al. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. American Cancer Society Detection and Treatment Advisory Group on Colorectal Cancer. CA Cancer J Clin 1997; 47:154–60PubMedCrossRef
3.
Zurück zum Zitat Mandel JS, Church TR, Bond JH, et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000; 343:1603–7PubMedCrossRef Mandel JS, Church TR, Bond JH, et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000; 343:1603–7PubMedCrossRef
4.
Zurück zum Zitat Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects. CA Cancer J Clin 2007; 57:90–104PubMed Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects. CA Cancer J Clin 2007; 57:90–104PubMed
5.
Zurück zum Zitat Castells A, Bessa X, Daniels M, et al. Value of postoperative surveillance after radical surgery for colorectal cancer: results of a cohort study. Dis Colon Rectum 1998; 41:714–23PubMedCrossRef Castells A, Bessa X, Daniels M, et al. Value of postoperative surveillance after radical surgery for colorectal cancer: results of a cohort study. Dis Colon Rectum 1998; 41:714–23PubMedCrossRef
6.
Zurück zum Zitat Ghossein RA, Bhattacharya S. Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours. Eur J Cancer 2000; 36:1681–94PubMedCrossRef Ghossein RA, Bhattacharya S. Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours. Eur J Cancer 2000; 36:1681–94PubMedCrossRef
7.
Zurück zum Zitat Ghossein RA, Bhattacharya S, Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin Cancer Res 1999; 5:1950–60PubMed Ghossein RA, Bhattacharya S, Rosai J. Molecular detection of micrometastases and circulating tumor cells in solid tumors. Clin Cancer Res 1999; 5:1950–60PubMed
8.
Zurück zum Zitat Weitz J, Kienle P, Lacroix J, et al. Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res 1998; 4:343–8PubMed Weitz J, Kienle P, Lacroix J, et al. Dissemination of tumor cells in patients undergoing surgery for colorectal cancer. Clin Cancer Res 1998; 4:343–8PubMed
9.
Zurück zum Zitat Wharton RQ, Jonas SK, Glover C, et al. Increased detection of circulating tumor cells in the blood of colorectal carcinoma patients using two reverse transcription-PCR assays and multiple blood samples. Clin Cancer Res 1999; 5:4158–63PubMed Wharton RQ, Jonas SK, Glover C, et al. Increased detection of circulating tumor cells in the blood of colorectal carcinoma patients using two reverse transcription-PCR assays and multiple blood samples. Clin Cancer Res 1999; 5:4158–63PubMed
10.
Zurück zum Zitat Yamaguchi K, Takagi Y, Aoki S, et al. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg 2000; 232:58–65PubMedCrossRef Yamaguchi K, Takagi Y, Aoki S, et al. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg 2000; 232:58–65PubMedCrossRef
11.
Zurück zum Zitat Patel H, Le Marer N, Wharton RQ, et al. Clearance of circulating tumor cells after excision of primary colorectal cancer. Ann Surg 2002; 235:226–31PubMedCrossRef Patel H, Le Marer N, Wharton RQ, et al. Clearance of circulating tumor cells after excision of primary colorectal cancer. Ann Surg 2002; 235:226–31PubMedCrossRef
12.
Zurück zum Zitat Wang JY, Wu CH, Lu CY, et al. Molecular detection of circulating tumor cells in the peripheral blood of patients with colorectal cancer using RT-PCR: significance in the prediction of postoperative metastasis. World J Surg 2006; 30:1007–13PubMedCrossRef Wang JY, Wu CH, Lu CY, et al. Molecular detection of circulating tumor cells in the peripheral blood of patients with colorectal cancer using RT-PCR: significance in the prediction of postoperative metastasis. World J Surg 2006; 30:1007–13PubMedCrossRef
13.
Zurück zum Zitat Hoon DS, Wang Y, Dale PS, et al. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol 1995; 13:2109–16PubMed Hoon DS, Wang Y, Dale PS, et al. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol 1995; 13:2109–16PubMed
14.
Zurück zum Zitat Racila E, Euhus D, Weiss AJ, et al. Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci USA 1998; 95:4589–94PubMedCrossRef Racila E, Euhus D, Weiss AJ, et al. Detection and characterization of carcinoma cells in the blood. Proc Natl Acad Sci USA 1998; 95:4589–94PubMedCrossRef
15.
Zurück zum Zitat Baker MK, Mikhitarian K, Osta W, et al. Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin Cancer Res 2003; 9:4865–71PubMed Baker MK, Mikhitarian K, Osta W, et al. Molecular detection of breast cancer cells in the peripheral blood of advanced-stage breast cancer patients using multimarker real-time reverse transcription-polymerase chain reaction and a novel porous barrier density gradient centrifugation technology. Clin Cancer Res 2003; 9:4865–71PubMed
16.
Zurück zum Zitat Sher YP, Shih JY, Yang PC, et al. Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes. Clin Cancer Res 2005; 11:173–9PubMed Sher YP, Shih JY, Yang PC, et al. Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes. Clin Cancer Res 2005; 11:173–9PubMed
17.
Zurück zum Zitat Chen YF, Wang JY, Wu CH, et al. Detecting circulating cancer cells with K-ras oncogene using membrane array. Cancer Lett 2005; 229:115–22PubMedCrossRef Chen YF, Wang JY, Wu CH, et al. Detecting circulating cancer cells with K-ras oncogene using membrane array. Cancer Lett 2005; 229:115–22PubMedCrossRef
18.
Zurück zum Zitat Wang JY, Yeh CS, Chen YF, et al. Development and evaluation of a colorimetric membrane-array method for the detection of circulating tumor cells in the peripheral blood of Taiwanese patients with colorectal cancer. Int J Mol Med 2006; 17:737–47PubMed Wang JY, Yeh CS, Chen YF, et al. Development and evaluation of a colorimetric membrane-array method for the detection of circulating tumor cells in the peripheral blood of Taiwanese patients with colorectal cancer. Int J Mol Med 2006; 17:737–47PubMed
19.
Zurück zum Zitat Yeh CS, Wang JY, Wu CH, et al. Molecular detection of circulating cancer cells in the peripheral blood of patients with colorectal cancer by using membrane array with a multiple mRNA marker panel. Int J Oncol 2006; 28:411–20PubMed Yeh CS, Wang JY, Wu CH, et al. Molecular detection of circulating cancer cells in the peripheral blood of patients with colorectal cancer by using membrane array with a multiple mRNA marker panel. Int J Oncol 2006; 28:411–20PubMed
20.
Zurück zum Zitat Wang JY, Lin SR, Wu DC, et al. Multiple molecular markers as predictors of colorectal cancer in patients with normal peri-operative serum CEA levels. Clin Cancer Res 2007; 13:2406–13PubMedCrossRef Wang JY, Lin SR, Wu DC, et al. Multiple molecular markers as predictors of colorectal cancer in patients with normal peri-operative serum CEA levels. Clin Cancer Res 2007; 13:2406–13PubMedCrossRef
21.
Zurück zum Zitat International Union Against Cancer. TNM classification of malignant tumors, 6th edition. New York: Wiley-Liss, Inc., 2002 International Union Against Cancer. TNM classification of malignant tumors, 6th edition. New York: Wiley-Liss, Inc., 2002
22.
Zurück zum Zitat Wu CH, Lin SR, Yu FJ, et al. Development of a high-throughput membrane-array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers. Int J Cancer 2006; 119:373–9PubMedCrossRef Wu CH, Lin SR, Yu FJ, et al. Development of a high-throughput membrane-array method for molecular diagnosis of circulating tumor cells in patients with gastric cancers. Int J Cancer 2006; 119:373–9PubMedCrossRef
23.
Zurück zum Zitat Uen YH, Lin SR, Wu DC, et al. Prognostic significance of multiple molecular markers for patients with stage II colorectal cancer undergoing curative resection. Ann Surg 2007; 246:1040–6PubMedCrossRef Uen YH, Lin SR, Wu DC, et al. Prognostic significance of multiple molecular markers for patients with stage II colorectal cancer undergoing curative resection. Ann Surg 2007; 246:1040–6PubMedCrossRef
24.
Zurück zum Zitat Iinuma H, Okinaga K, Egami H, et al. 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. Int J Oncol 2006; 28:297–306PubMed Iinuma H, Okinaga K, Egami H, et al. 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. Int J Oncol 2006; 28:297–306PubMed
25.
Zurück zum Zitat Guller U, Zajac P, Schnider A, et al. 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; 236:768–75PubMedCrossRef Guller U, Zajac P, Schnider A, et al. 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; 236:768–75PubMedCrossRef
26.
Zurück zum Zitat Liefers GJ, Cleton-Jansen AM, van de Velde CJ, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med 1998; 339:223–8PubMedCrossRef Liefers GJ, Cleton-Jansen AM, van de Velde CJ, et al. Micrometastases and survival in stage II colorectal cancer. N Engl J Med 1998; 339:223–8PubMedCrossRef
27.
Zurück zum Zitat Koch M, Kienle P, Kastrati D, et al. Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancer. Int J Cancer 2006; 118:3072–7PubMedCrossRef Koch M, Kienle P, Kastrati D, et al. Prognostic impact of hematogenous tumor cell dissemination in patients with stage II colorectal cancer. Int J Cancer 2006; 118:3072–7PubMedCrossRef
28.
Zurück zum Zitat Bessa X, Elizalde JI, Boix L, et al. Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer. Gastroenterology 2001; 120:1084–92PubMedCrossRef Bessa X, Elizalde JI, Boix L, et al. Lack of prognostic influence of circulating tumor cells in peripheral blood of patients with colorectal cancer. Gastroenterology 2001; 120:1084–92PubMedCrossRef
29.
Zurück zum Zitat Bosch B, Guller U, Schnider A, et al. Perioperative detection of disseminated tumor cells is an independent prognostic factor in patients with colorectal cancer. Br J Surg 2003; 90:882–8PubMedCrossRef Bosch B, Guller U, Schnider A, et al. Perioperative detection of disseminated tumor cells is an independent prognostic factor in patients with colorectal cancer. Br J Surg 2003; 90:882–8PubMedCrossRef
30.
Zurück zum Zitat Khair G, Monson JR, Greenman J. Epithelial molecular markers in the peripheral blood of patients with colorectal cancer. Dis Colon Rectum 2007; 50:1188–203PubMedCrossRef Khair G, Monson JR, Greenman J. Epithelial molecular markers in the peripheral blood of patients with colorectal cancer. Dis Colon Rectum 2007; 50:1188–203PubMedCrossRef
31.
Zurück zum Zitat Fidler IJ. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo–2′-deoxyuridine. J Natl Cancer Inst 1970; 45:773–82PubMed Fidler IJ. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125 I-5-iodo–2′-deoxyuridine. J Natl Cancer Inst 1970; 45:773–82PubMed
32.
Zurück zum Zitat Sadahiro S, Suzuki T, Maeda Y, et al. Detection of carcinoembryonic antigen messenger RNA-expressing cells in peripheral blood 7 days after curative surgery is a novel prognostic factor in colorectal cancer. Ann Surg Oncol 2007; 14:1092–8PubMedCrossRef Sadahiro S, Suzuki T, Maeda Y, et al. Detection of carcinoembryonic antigen messenger RNA-expressing cells in peripheral blood 7 days after curative surgery is a novel prognostic factor in colorectal cancer. Ann Surg Oncol 2007; 14:1092–8PubMedCrossRef
33.
Zurück zum Zitat Allen-Mersh TG, McCullough TK, Patel H, et al. Role of circulating tumour cells in predicting recurrence after excision of primary colorectal carcinoma. Br J Surg 2007; 94:96–105PubMedCrossRef Allen-Mersh TG, McCullough TK, Patel H, et al. Role of circulating tumour cells in predicting recurrence after excision of primary colorectal carcinoma. Br J Surg 2007; 94:96–105PubMedCrossRef
34.
Zurück zum Zitat Silva JM, Rodriguez R, Garcia JM, et al. Detection of epithelial tumour RNA in the plasma of colon cancer patients is associated with advanced stages and circulating tumour cells. Gut 2002; 50:530–4PubMedCrossRef Silva JM, Rodriguez R, Garcia JM, et al. Detection of epithelial tumour RNA in the plasma of colon cancer patients is associated with advanced stages and circulating tumour cells. Gut 2002; 50:530–4PubMedCrossRef
Metadaten
Titel
Persistent Presence of Postoperative Circulating Tumor Cells is a Poor Prognostic Factor for Patients with Stage I–III Colorectal Cancer after Curative Resection
verfasst von
Yih-Huei Uen, MD
Chien-Yu Lu, MD
Hsiang-Lin Tsai, MD
Fang-Jung Yu, MD
Ming-Yii Huang, MD
Tian-Lu Cheng, PhD
Shiu-Ru Lin, PhD
Jaw-Yuan Wang, MD, PhD
Publikationsdatum
01.08.2008
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 8/2008
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-008-9961-7

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