Brief Article
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World J Gastroenterol. Oct 14, 2010; 16(38): 4823-4831
Published online Oct 14, 2010. doi: 10.3748/wjg.v16.i38.4823
Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients
Inti Zlobec, Francesca Molinari, Vittoria Martin, Luca Mazzucchelli, Piercarlo Saletti, Rosangela Trezzi, Sara De Dosso, Tatjana Vlajnic, Milo Frattini, Alessandro Lugli
Inti Zlobec, Tatjana Vlajnic, Alessandro Lugli, Institute for Pathology, University Hospital Basel, Basel 4031, Switzerland
Francesca Molinari, Vittoria Martin, Luca Mazzucchelli, Rosangela Trezzi, Milo Frattini, Institute of Pathology, Locarno 6600, Switzerland
Piercarlo Saletti, Sara De Dosso, Division of Medical Oncology, Institute of Southern Switzerland, Bellinzona 6500, Switzerland
Author contributions: Zlobec I was responsible for study design, statistical analysis and data interpretation; Lugli A was responsible for study design and data interpretation; Vlajnic T was responsible for histological evaluation; Molinari F, Martin V, Mazzucchelli L and Frattini M were responsible for molecular analysis and interpretation; all authors contributed to manuscript editing and final approval.
Correspondence to: Dr. Inti Zlobec, PhD, Institute for Pathology, University Hospital Basel, Schoenbeinstrasse 40, Basel, 4031, Switzerland.
Telephone: +41-61-2652895 Fax: +41-61-2652966
Received: May 20, 2010
Revised: July 9, 2010
Accepted: July 16, 2010
Published online: October 14, 2010

AIM: To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients.

METHODS: Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and “high-grade” tumor budding was defined as 15 buds/high-power field.

RESULTS: Tumor buds and K-RAS mutation both correctly classified 68% of patients. All patients with K-RAS mutation (n = 7) or high-grade tumor budding (n = 11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P = 0.008)].

CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting.

Keywords: Anti-epidermal growth factor receptor therapy, Colorectal cancer, K-RAS, Prognosis, Tumor budding