TUMOR BUDDING IN COLORECTAL CANCER CLINICAL APPROACH Prof. A. Lugli, MD Division of Clinical Pathology University of Bern Symposium de Gastroentérologie Aurigen Lausanne, April 10 th 2014
CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION
THE IMPORTANCE OF TUMOR MICROENVIRONMENT Hanahan and Weinberg, Cell 2011
THE TUMOR MICROENVIRONMENT Hanahan and Weinberg. Cell 2011
TUMOR BUDS Definition Single tumor cells or cluster up to 5 tumor cells at the invasive margin EMT like cells Transformation to a motile and invasive phenotype Low proliferation Potentially malignant stem cells
TUMOR BUDS Phenotype MUC1 p16 b-cat E-Cad
TUMOR BUDS Low proliferation Dawson et al, Histopathology 2014
TUMOR BUDS Stem cell character? Hostettler et al, WJG 2010
TUMOR BUDS CREED CRC s special force Detachment Loss of E-Cadherin Stroma migration MMP-2, MMP-9 Activated wnt Nuclear b-catenin Angiogenesis & vessel affinity VEGF, CXC3&4 Low proliferation Loss of Ki-67 Stem cell like CD133, ABCG5 Zlobec & Lugli, Oncotarget 2010
Zlobec & Lugli. Oncotarget 2010
CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION
TUMOR BUDDING AND PROGNOSIS A marker of tumor progression Lymph node metastasis Ueno et al. Gastroenterology 2004 Kazama et al. Br J Cancer 2006 Distant metastasis Nakamura et al. DCR 2008 Prall et al. Histopathology 2005 Lymphovascular invasion Lugli et al. Br J Cancer 2009 Ishikawa et al. Cancer 2008 Local recurrence Tanaka et al. DCR 2003 Guzinska-Ustimowicz. AntiC Research 2005
TUMOR BUDDING AND PROGNOSIS Independent of the applied scoring system Authors Journal Sample Size CRC Stage Prognostic factor Morodomi et al. Cancer 1989 112 I - IV Yes Hase et al. Dis C&R 1993 663 I - IV Yes Ueno et al. Histopathology 2002 638 I - IV Yes Ueno et al. Cancer 437 I - IV Yes Jass et al. J Clin Pathol 2003 80 I - IV Yes Okuyama et al. J Surg Oncol 2003 83 II / III Yes Okuyama et al. Dis C&R 2003 196 II / III Yes Park et al. Dis C&R 2005 174 I - IV Yes Prall et al. Histopathology 2005 186 I / II Yes Hörkkö et al. Eur J Cancer 2006 466 I - IV Yes Shinto et al. Dis C&R 2006 136 II / III Yes Masaki et al. J Gastro & Hepatol 2006 76 I Yes Choi et al. Int J Colorectal Dis 2007 244 III Yes Konazawa et al. Colorect Diss 2008 159 I - IV Yes Nakamura et al. Dis C&R 2008 200 II Yes Ohtsuki et al. Anticancer Res 2008 149 I - IV Yes Wang et al. Am J Surg Pathol 2009 126 II Yes Lugli et al. Br J Cancer 2010 470 I - IV Yes Sy et al. Dis C&R 2010 477 III No
TUMOR BUDDING AND PROGNOSIS UICC Classification Prognostic Factor Tumor-related Host-related Environment related Essential T category N category M category Venous/lymphatic invasion Obstruction Quality of surgery Quality of TME (rectal cancer) Additional Grade, tumor budding, border configuration, perineural invasion, medullary type, CEA, perforation Thrombocytosis Diabetes mellitus Number of lymph nodes in resection specimen New and promising MSI LOH 18q status P53 DNA ploidy TGFbeta1 type II Thymidylate synthase polymorphism VEGF expression 20q copy number, Karyotype Proliferation rate, Metalloproteinase expression, Gene expression profiles Compton C. Prognostic Factors in colorectal cancer edited by Gospodarowicz, O Sullivan and Sobin, 3 rd edition, 2006
TUMOR BUDDING AND PROGNOSIS WHO Classification
PREDICTIVE VALUE OF TUMOR BUDDING Anti-EGFR therapy Zlobec et al, WJG 2010
CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION
TUMOR BUDDING Scoring system 10 HPF Method Horcic et al, Hum Pathol 2011
TUMOR BUDDING 10 HPF Method Horcic et al, Hum Pathol 2011
TUMOR BUDDING Validation of the 10 HPF Method Karamitopoulou et al, Mod Pathol 2012
ITB AND PTB pt1 CRC Ueno et al, Gastroenterology 2004
PERITUMORAL BUDDING (PTB) Resections Stage II CRC n = 128 T3N0M0 Wang et al, Am J Surg Pathol 2009
INTRATUMORAL BUDDING (ITB) Concept: 2 independent cohorts: n=289 and 222 Intratumoural Budding (ITB) + Peritumoural Budding PTB) = Overall Tumour Budding (OTB) Lugli et al, Human Pathol 2011
INTRATUMORAL BUDDING (ITB) 1 HPF Method Zlobec et al, BJC 2013
INTRATUMORAL BUDDING (ITB) Preoperative biopsies
CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION
POINTS TO CONSIDER Tumor budding is an independent adverese prognostic factor ITB has to be distinguished from PTB A standardized scoring system is important, but not mandatory The fields of action may include stage II CRC, pt1 CRC and preoperative biopsies
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