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.
OBJECTIVE
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.


METHODS
We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin gamma2, 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.


CONCLUSIONS
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.
Lloyd
Julia M
JM
Department of Haematology-Oncology, Hetzel Institute, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, SA 5011, Australia.
McIver
Cassandra M
CM
Stephenson
Sally-Anne
SA
Hewett
Peter J
PJ
Rieger
Nicholas
N
Hardingham
Jennifer E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D005260:Female; D006801:Humans; D053554:Keratin-20; D007633:Keratins / Q000097:blood / Q000235:genetics; D007797:Laminin / Q000097:blood / Q000235:genetics; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics; D009367:Neoplasm Staging; D010533:Peritoneal Lavage; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D036081:Receptors, Eph Family / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; C507499:KRT20 protein, human; D053554:Keratin-20; C400567:LAMC2 protein, human; D007797:Laminin; D012333:RNA, Messenger; D007633:Keratins; D036081:Receptors, Eph Family; D020783:Matrix Metalloproteinase 7