Combining Molecular Markers With the TNM Staging System to Improve Prognostication in Stage II and III Colon Cancer: Are We Ready Yet?
Menée sur des échantillons tumoraux prélevés sur 1 404 patients atteints d'un cancer du côlon de stade II/III et inclus dans l'essai PETACC3 évaluant une chimiothérapie adjuvante, cette étude évalue l'intérêt d'une analyse intégrée de marqueurs moléculaires et cliniques pour le pronostic de la maladie
In this issue of the Journal, Roth and colleagues report a study entitled “Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer.” The study population consisted of participants in a randomized adjuvant therapy trial (PETACC-3) that evaluated 5-fluorouracil and leucovorin alone or combined with irinotecan in curatively resected stage II and stage III colon cancer patients. In prospectively collected tumor tissue from a subset (420 stage II; 984 stage III) of the overall cohort (N = 3278), molecular markers, including microsatellite instability (MSI), BRAF V600E and KRAS mutation status, chromosome 18q loss of heterozygosity (LOH), and SMAD4 protein expression, were analyzed and their association with clinical outcome was determined. Importantly, all biomarker assays were performed in the same laboratory. Biomarkers were chosen based upon promising data for their potential prognostic impact in nonmetastatic colon cancer patients. To date, none of the biomarkers evaluated in this study are considered to have been sufficiently validated for prognostication in routine clinical practice. The primary objective of the study by Roth et al. was to determine whether any of these five biomarkers can refine the established TNM staging system by identifying prognostic subgroups that may improve upon the accuracy of TNM staging to predict clinical outcome.
Prior reports from the PETACC-3 biomarker cohort and other retrospective studies have shown that MSI-high (MSI-H) stage II and stage III colon cancers are associated with more favorable survival than MSI-low (MSI-L) and microsatellite-stable (MSS) cancers. Most MSI-H colorectal cancers are sporadics that show epigenetic inactivation of the MHL1 gene and carry mutations in the BRAF V600E oncogene in up to 50% of tumors that are mutually exclusive with KRAS mutations (4). Studies examining the …
Journal of the National Cancer Institute , éditorial, 2012