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DOI: 10.1200/JCO.2007.11.8182

Molecular Biology for Stage II

Colorectal Cancer: The Jury Is
Still Out
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 althe 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.

Stefano Cascinu
Clinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Universita`
Politecnica delle Marche, Ancona, Italy

Alberto Zaniboni
Oncologia Medica, Casa di Cura Poliambulanza, Brescia, Italy

Mario Scartozzi
Clinica di Oncologia Medica, Azienda Ospedaliera Ospedali Riuniti-Universita`
Politecnica delle Marche, Ancona, Italy

Fausto Meriggi
Oncologia Medica, Casa di Cura Poliambulanza, Brescia, Italy

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 DukesB colon cancer. J Clin Oncol 22:15641571, 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

DOI: 10.1200/JCO.2006.10.0966

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