The relationship between genetic profiling, clinicopathological factors and survival in patients undergoing surgery for node-negative colorectal cancer: 10-year follow-up.
OBJECTIVE
The introduction of the bowel cancer screening programme has resulted in increasing numbers of patients being diagnosed with node-negative disease. Unfortunately, approximately 30 % will develop recurrence following surgery. Given the toxicity associated with adjuvant chemotherapy, it is important to identify high-risk patients who may benefit from adjuvant therapy. This study aims to identify which clinicopathological factors and genetic profiling markers predict outcome in node-negative disease.


METHODS
Forty-nine microsatellite stable (MSS) patients undergoing curative resection between 1991 and 1993 were included. Local immune response was assessed by Klintrup criteria and vascular invasion status assessed through Miller's elastin staining. Comparative genomic hybridisation (CGH) on a range of loci provided data on allelic imbalance. Analysis of survival included clinicopathological and CGH data in a multivariate (Cox) model.


RESULTS
On binary logistical regression analysis, 4p deletion was independently associated with low Klintrup score (HR 0.16; 95 % CI (0.03-0.96); P = 0.045), venous invasion (HR 4.19; 95 % CI (1.08-16.29); P = 0.039) and higher Dukes' stage (HR 6.43; 95 % CI (1.22-33.97); P = 0.028). Minimum follow-up was 109 months and there were 24 cancer deaths. On multivariate analysis, high Klintrup score (HR 0.33; 95 % CI (0.12-0.93); P = 0.036), 4p- (HR 4.01; 95 % CI (1.58-10.21); P = 0.004) and 5q- (HR 3.81; 95 % CI (1.54-9.47); P = 0.004) were significantly associated with survival.


CONCLUSIONS
4p-, 5q- and low Klintrup score were independently associated with poor cancer-specific survival in node-negative MSS colorectal cancer. Confirmatory work in a larger cohort is needed to determine whether these markers may be used to identify patients who may benefit from adjuvant chemotherapy.
Unit of Experimental Therapeutics, Institute of Cancer Science, University of Glasgow, McGregor Building, Western Infirmary Glasgow, Glasgow, G11 6NT, UK, arfon.powell@glasgow.ac.uk.
Arfon G M T
AG
Powell
Jenny
J
Ferguson
Fahd
F
Al-Mulla
Clare
C
Orange
Donald C
DC
McMillan
Paul G
PG
Horgan
Joanne
J
Edwards
James J
JJ
Going
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D042822:Genomic Instability / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D059467:Transcriptome