PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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.
Authors: Kai Klintrup; Johanna M Mäkinen; Saila Kauppila; Päivi O Väre; Jukka Melkko; Hannu Tuominen; Karoliina Tuppurainen; Jyrki Mäkelä; Tuomo J Karttunen; Markus J Mäkinen Journal: Eur J Cancer Date: 2005-10-18 Impact factor: 9.162
Authors: J Richter; U Wagner; P Schraml; R Maurer; G Alund; H Knönagel; H Moch; M J Mihatsch; T C Gasser; G Sauter Journal: Cancer Res Date: 1999-11-15 Impact factor: 12.701
Authors: Laurent Pangon; Nicholas D Sigglekow; Mark Larance; Sam Al-Sohaily; Dessislava N Mladenova; Christina I Selinger; Elizabeth A Musgrove; Maija R J Kohonen-Corish Journal: Genes Cancer Date: 2010-09
Authors: Claus Rödel; Gerhard G Grabenbauer; Thomas Papadopoulos; Marc Bigalke; Klaus Günther; Christoph Schick; Andrea Peters; Rolf Sauer; Franz Rödel Journal: Int J Radiat Oncol Biol Phys Date: 2002-02-01 Impact factor: 7.038
Authors: Timothy K Starr; Raha Allaei; Kevin A T Silverstein; Rodney A Staggs; Aaron L Sarver; Tracy L Bergemann; Mihir Gupta; M Gerard O'Sullivan; Ilze Matise; Adam J Dupuy; Lara S Collier; Scott Powers; Ann L Oberg; Yan W Asmann; Stephen N Thibodeau; Lino Tessarollo; Neal G Copeland; Nancy A Jenkins; Robert T Cormier; David A Largaespada Journal: Science Date: 2009-02-26 Impact factor: 47.728