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Journal of Clinical Oncology, Vol 25, No 19 (July 1), 2007: pp. 2861 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.10.0966
Molecular Biology for Stage II Colorectal Cancer: The Jury Is Still OutClinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
Oncologia Medica, Casa di Cura Poliambulanza, Brescia, Italy
Clinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy
Oncologia Medica, Casa di Cura Poliambulanza, Brescia, Italy To the Editor: We read with great interest the recent article by Barrier et al1 in the Journal of Clinical Oncology. Although the data presented might be of great value for the development of innovative prognostic indicators in early stage colorectal cancer, we think that few observations are to be made. The article questions the role of gene expression profiling as a predictive tool for prognosis in stage II colon cancer analogously to what has been already described in a similar article by Wang et al2 published in the Journal of Clinical Oncology in 2004. In fact in the article by Barrier et al, 50 patients with stage II colon cancer, not receiving adjuvant chemotherapy, were analyzed using the same microarray gene expression profiling tool investigated by Wang et al—the HGU133 Genechip (Affymetrix, Santa Clara, CA). Nevertheless, unlike Wang et al who found that a 23-gene prognosis signature (PS) was able to identify high-risk patients,1,2 Barrier et al emphasized that a 30-gene PS might perform better than the 23-gene PS and should represent a starting point for future prospective studies. However, when we compare the composition of the 30- and 23-gene PSs identified in the Barrier and Wang studies, respectively, we can easily note that totally different genes have been indicated and analyzed in the two different PSs. This should imply that, on the one hand, we are able to retrospectively identify higher risk stage II colon tumors, but on the other hand, the prospective use of such an approach could be rather difficult, if not totally unfeasible, in future studies of adjuvant chemotherapy on biologically selected early stage colorectal cancer patients. We believe that the authors should comment more exhaustively on how these major flaws would seriously impair the use of this approach in the clinical setting. Another reason for concern arises from the apparent lack of comparison between molecular data and well-known pathologic and clinical features that have been unanimously recognized as prognostic determinants in these groups of patients. In fact the American Society of Clinical Oncology suggested that patients with stage II colon cancer presenting with fewer than 13 examined lymph nodes, a poorly differentiated tumor (G3), or perforation as clinical presentation, should be considered at high risk for relapse.3 Nevertheless, in the article by Wang et al, the patients categorized as at high risk, on the basis of the genomic profiling, were those with a suboptimal assessment of lymph node status, while patients at low risk for recurrence were those with optimally resected lymph nodes (median number of resected lymph nodes, 12). More importantly, in the analysis by Barrier et al, we were not able to find any information about the number of examined lymph nodes, the presence of vascular invasion, pT4 stage, or perforation. Only tumor differentiation was mentioned. This strongly suggests the opportunity for a more cautious statistical analysis balancing innovative parameters (ie, gene profiling) and well-known prognostic factors. It would be extremely surprising if a high technology assessment could give prognostic information similar to that obtained with a surely less elegant but undoubtedly more widely available analysis technique. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Barrier A, Boelle PY, Roser F, et al: Stage II colon cancer prognosis prediction by tumor gene expression profiling. J Clin Oncol 24:4685-4691, 2006 2. Wang Y, Jatkoe T, Zhang Y, et al: Gene expression profiling and molecular markers to predict recurrence of Dukes'B colon cancer. J Clin Oncol 22:1564-1571, 2004 3. Benson AB III, Schrag D, Somerfield MR, et al: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408-3419, 2004
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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