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Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

World Journal of Gastroenterology 2010年第38期16卷 4823-4831页

作者： Inti Zlobec Francesca Molinari Vittoria Martin Luca Mazzucchelli piercarlo saletti Rosangela Trezzi Sara De Dosso Tatjana Vlajnic Milo Frattini Alessandro Lugli Institute for Pathology University Hospital Basel Institute of Pathology Division of Medical Oncology Institute of Southern Switzerland

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 defi ned as 15 buds/high-power f ***: Tumor buds and K-RAS mutation both correctly classif ied 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.

关键词： Anti-epidermal growth factor receptor therapy Colorectal cancer K-RAS Prognosis Tumor budding

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