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| 1 | Invasive front of colorectal cancer:Dynamic interface of pro-/anti-tumor factors显示文摘Tumor-host interaction at the invasive front of colorectal cancer represents a critical interface encompassing a dynamic process of de-differentiation of colorectal carci-noma cells known as epithelial mesenchymal transition (EMT). EMT can be identified histologically by the presence of 'tumor budding' ,a feature which can be highly specific for tumors showing an inf iltrating tumor growth pattern. Importantly,tumor budding and tumor border configuration have generated considerable interest as additional prognostic factors and are also recognized as such by the International Union Against Cancer. Evidence seems to suggest that the presence of tumor budding or an infiltrating growth pattern is inversely correlated with the presence of immune and inflammatory responses at the invasive tumor front. In fact,several tumor-associated antigens such as CD3,CD4,CD8,CD20,Granzyme B,FOXP3 and other immunological or inflammatory cell types have been identified as poten-tially prognostic in patients with this disease. Evidence seems to suggest that the balance between protumor (including budding and inf iltrating growth pattern) and anti-tumor (immune response or certain inflammatory cell types) factors at the invasive front of colorectal cancer may be decisive in determining tumor progression and the clinical outcome of patients with colorectal cancer. On one hand,the inf iltrating tumor border configuration and tumor budding promote progression and dissemination of tumor cells by penetrating the vascular and lymphatic vessels. On the other,the host attempts to fend off this attack by mounting an immune response to protect vascular and lymphatic channels from invasion by tumor buds. Whereas standard pathology reporting of breast and prostate cancer involves additional prognostic features,such as the BRE and Gleason scores,the ratio of pro-and anti-tumor factors could be a promising approach for the future development of a prognostic score for patients with colorectal cancer which could complement tumor node metastasis staging to improve the clinical management of patients with this disease. | Inti Zlobec Alessandro Lugli | 2009 | World Journal of Gastroenterology2009，15，47： | 9 |
| 2 | Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients显示文摘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 ield.RESULTS: 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. | Inti Zlobec Francesca Molinari Vittoria Martin Luca Mazzucchelli Piercarlo Saletti Rosangela Trezzi Sara De Dosso Tatjana Vlajnic Milo Frattini Alessandro Lugli | 2010 | World Journal of Gastroenterology2010，16，38： | 4 |
| 3 | Possible role of Cdx2 in the serrated pathway of colorectal cancer characterized by BRAF mutation, high‐level CpG Island methylator phenotype and mismatch repair‐deficiency显示文摘 | Heather Dawson José A. Galván Melina Helbling Dominique‐Elisabeth Muller Eva Karamitopoulou Viktor H. Koelzer Mary Economou Caroline Hammer Alessandro Lugli Inti Zlobec | 2014 | Int. J. Cancer2014，，10： | 2 |
| 4 | ABCG5-positivity in tumor buds is an indicator of poor prognosis in node-negative colorectal cancer patients显示文摘AIM:To analyze the expression of 8 putative cancer stem cell(CSC) markers within colorectal cancer tumor buds and to determine their prognostic impact in patients with this disease. METHODS:Immunohistochemistry was performed on 101 colorectal cancer resections for CK22(to identify tumor buds) as well as CD133,CD166,CD24,CD44s,CD90,EpCAM,ALDH1,and ABCG5,and their expression within tumor buds was evaluated. RESULTS:CD90,CD44s,and CD133 expression in tumor buds was found in less than 5%of all cases. ALDH1,CD24,CD166 were expressed in 16.5%,16.2%,and 34%cases,respectively,while ABCG5 and EpCAM expression was more frequent and found in 35%and 69%of cases,respectively.Of the 8 markers studied,EpCAM and ABCG5 positivity in tumor buds were significantly associated with poor prognosis(P=0.023,P=0.038,respectively) in multivariable analysis with pT and pN classificationP=0.048;hazard ratio(HR) :2.64;95%CI:1.0-6.9,for EpCAM and P=0.029;HR:2.22;95%CI:1.0-4.5,for ABCG5.Poor survival time was particularly striking for lymph node-negative patients with ABCG5-positive buds(P<0.001) . CONCLUSION:Expression of putative stem cell markers EpCAM and ABCG5 within the tumor buds of colorectal cancer are frequently noted and are associated with poor prognosis. | lsabel Hostettler Inti Zlobec Luigi Terracciano Alessandro Lugli | 2010 | World Journal of Gastroenterology2010，16，6： | 2 |
| 5 | Clinical impact of programmed cell death ligand 1 expression in colorectal cancer显示文摘 | Raoul A. Droeser Christian Hirt Carsten T. Viehl Daniel M. Frey Christian Nebiker Xaver Huber Inti Zlobec Serenella Eppenberger-Castori Alexander Tzankov Raffaele Rosso Markus Zuber Manuele Giuseppe Muraro Francesca Amicarella Eleonora Cremonesi Michael H | 2013 | European Journal of Cancer2013，，9： | 1 |
| 6 | Systematic analysis of proteins from different signaling pathways in the tumor center and the invasive front of colorectal cancer显示文摘 | Eva Karamitopoulou Inti Zlobec Ioannis Panayiotides Efstratios S. Patsouris George Peros George Rallis Christos Lapas Petros Karakitsos Luigi M. Terracciano Alessandro Lugli | 2011 | Human Pathology2011，，12： | 1 |
| 7 | Comprehensive analysis of CpG island methylator phenotype (CIMP)-high,-low, and - negative colorectal cancers based on protein marker expression and mo- lecular features 显示文摘 | ZLOBEC INTI BIHL MICHEL FOERSTER | 2011 | J Patho12011，225，3： | 1 |
| 8 | Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours显示文摘 | Jér?me Galon Bernhard Mlecnik Gabriela Bindea Helen K Angell Anne Berger Christine Lagorce Alessandro Lugli Inti Zlobec Arndt Hartmann Carlo Bifulco Iris D Nagtegaal Richard Palmqvist Giuseppe V Masucci Gerardo Botti Fabiana Tatangelo Paolo Delrio Michele | 2014 | Pathol2014，，2： | 1 |
| 9 | Klf4 transcription factor is expressed in the cytoplasm of prostate cancer cells显示文摘 | Clémentine Le Magnen Lukas Bubendorf Christian Ruiz Inti Zlobec Alexander Bachmann Michael Heberer Giulio C. Spagnoli Stephen Wyler Chantal Mengus | 2012 | European Journal of Cancer2012，，： | 1 |
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