Identification of Early-Stage Colorectal Cancer Patients at Risk of Relapse Post-Resection by Immunobead Reverse Transcription-PCR Analysis of Peritoneal Lavage Fluid for Malignant Cells

Abstract

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin g2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer.This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer.

Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer

“…Patients with high CEA levels may have as yet undetected occult metastases at the time of the operation. Lloyd et al [23] reported that, of stage I and II patients, 32.8% tested positive for disseminated tumor cells after surgery, and patients who were marker-positive for disseminated cells in postresection lavage samples showed a significantly poorer prognosis. These reports suggested that residual tumor cells might be present even though curative resection was performed.…”

Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review

“…The 14 studies included here comprised 1841 patients in total, with the median number of patients in each study being 99.5 (range 42 -438) (Taniguchi et al, 2000;Yamaguchi et al, 2000;Ito et al, 2002;Bessa et al, 2003;Chen et al, 2004;Sadahiro et al, 2005Sadahiro et al, , 2007Katsumata et al, 2006;Koch et al, 2006;Lloyd et al, 2006;Allen-Mersh et al, 2007;Uen et al, 2007Uen et al, , 2008Wang et al, 2007).…”

“…Of the 14 studies included, eight undertook blood sampling perioperatively (Taniguchi et al, 2000;Yamaguchi et al, 2000;Ito et al, 2002;Chen et al, 2004;Sadahiro et al, 2005;Katsumata et al, 2006;Koch et al, 2006;Lloyd et al, 2006), four undertook sampling approximately 24 h after resection (Bessa et al, 2003;Koch et al, 2006;Lloyd et al, 2006;Allen-Mersh et al, 2007), and six undertook sampling between 24 h and 14 days after resection (Chen et al, 2004; Allen-Mersh et al, 2007;Sadahiro et al, 2007;Uen et al, 2007Uen et al, , 2008Wang et al, 2007).…”

MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer

“…In cancer immunology, a clear role of MMP7 and of other MMPs has been shown in tumour growth and invasion (17,(20)(21)(22)(23)(24)(25). Increased MMP7 expression in tumour tissue, serum, lymph nodes and peritoneal liquid generally correlates with worse prognosis, a tendency for metastatic disease and reduced overall survival (18,(26)(27)(28)(29)(30)(31)(32). This suggests a possible role for MMP7 in the determination of locally advanced cancer in resected specimens, and in staging and planning for eventual adjuvant therapy, attesting to a potential role of MMP7 as prognostic factor and tumour marker (33) The effect of RT on MMP7 gene in human rectal cancer was first investigated in vivo by Kumar et al, who observed overexpression of MMP7 in radiated rectal cancer tissue compared to nearby irradiated normal rectal tissue (9).…”