A pathology sub-study of putative prognostic markers in colorectal cancer.

, Dr SA Grumett MDa, Professor P Quirke MD PhDb, Professor DJ Kerr MD PhDc, Mr C McConkey PhDa, Dr J Stahlsmidt MDb, Dr J Barnwell PhDa.

1 Institute for Cancer Studies, University of Birmingham, UK. 2 Department of Pathology, University of Leeds, UK c Department of Clinical Pharmacology, University of Oxford, UK.

AIM: To identify potential prognostic histopathological and molecular markers of prognosis in colorectal cancer. METHODS: 403 paraffin embedded tumour blocks were collected from patients with Dukes B and C colorectal cancer in the Quasar trial of adjuvant chemotherapy. These were analysed by light microscopy for histological factors such as TNM stage, vascular invasion and lymphocytic infiltration and by immunohistochemistry for p53, thymidylate synthase, hMLH-1, hMSH-2 and dUTPase. A further 400 blocks are being analysed as above, and in addition for DNA ploidy by nuclear typing. RESULTS: Data were analysed by proportional hazards modelling and log rank testing with respect to recurrence. Dukes stage was associated with an increased risk of recurrence (p<0.001), as was the presence of vascular invasion (p=0.01) and pT4 stage (p=0.02) but high thymidylate synthase expression was associated with a lower risk (p=0.02). No other factor reached significance, although microsatellite instability showed a trend, with a high MSH-2 score being associated with a higher risk of recurrence (p=0.08) Mean follow up for the patients was 46 months. CONCLUSIONS: Vascular invasion and thymidylate synthase expression are significantly associated with risk of recurrence in this population of, mainly Dukes B (96%), colorectal cancer patients. The data from the analysis of the subsequent 400 blocks, and the maturation of the outcome data, will strengthen these conclusions.

KEY WORDS: Colorectal neoplasms, prognosis.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.