TUMOR BUDDING IN COLORECTAL CANCER

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1 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

2 CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION

3 THE IMPORTANCE OF TUMOR MICROENVIRONMENT Hanahan and Weinberg, Cell 2011

4 THE TUMOR MICROENVIRONMENT Hanahan and Weinberg. Cell 2011

5 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

6 TUMOR BUDS Phenotype MUC1 p16 b-cat E-Cad

7 TUMOR BUDS Low proliferation Dawson et al, Histopathology 2014

8 TUMOR BUDS Stem cell character? Hostettler et al, WJG 2010

9 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

10 Zlobec & Lugli. Oncotarget 2010

11 CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION

12 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

13 TUMOR BUDDING AND PROGNOSIS Independent of the applied scoring system Authors Journal Sample Size CRC Stage Prognostic factor Morodomi et al. Cancer I - IV Yes Hase et al. Dis C&R I - IV Yes Ueno et al. Histopathology I - IV Yes Ueno et al. Cancer 437 I - IV Yes Jass et al. J Clin Pathol I - IV Yes Okuyama et al. J Surg Oncol II / III Yes Okuyama et al. Dis C&R II / III Yes Park et al. Dis C&R I - IV Yes Prall et al. Histopathology I / II Yes Hörkkö et al. Eur J Cancer I - IV Yes Shinto et al. Dis C&R II / III Yes Masaki et al. J Gastro & Hepatol I Yes Choi et al. Int J Colorectal Dis III Yes Konazawa et al. Colorect Diss I - IV Yes Nakamura et al. Dis C&R II Yes Ohtsuki et al. Anticancer Res I - IV Yes Wang et al. Am J Surg Pathol II Yes Lugli et al. Br J Cancer I - IV Yes Sy et al. Dis C&R III No

14 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

15 TUMOR BUDDING AND PROGNOSIS WHO Classification

16 PREDICTIVE VALUE OF TUMOR BUDDING Anti-EGFR therapy Zlobec et al, WJG 2010

17 CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION

18 TUMOR BUDDING Scoring system 10 HPF Method Horcic et al, Hum Pathol 2011

19 TUMOR BUDDING 10 HPF Method Horcic et al, Hum Pathol 2011

20 TUMOR BUDDING Validation of the 10 HPF Method Karamitopoulou et al, Mod Pathol 2012

21 ITB AND PTB pt1 CRC Ueno et al, Gastroenterology 2004

22 PERITUMORAL BUDDING (PTB) Resections Stage II CRC n = 128 T3N0M0 Wang et al, Am J Surg Pathol 2009

23 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

24 INTRATUMORAL BUDDING (ITB) 1 HPF Method Zlobec et al, BJC 2013

25 INTRATUMORAL BUDDING (ITB) Preoperative biopsies

26 CONTENT BIOLOGY OF TUMOR BUDDING PROGNOSTIC AND PREDICTIVE IMPACT SURGICAL PATHOLOGY OF TUMOR BUDDING CONCLUSION

27 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

29 THANK YOU FOR YOUR ATTENTION!

CHAPTER 14 STAGING AND REPORTING

CHAPTER 14 STAGING AND REPORTING Staging of Colorectal Cancer refers to the classification of the tumour according to the extent of spread in a manner that has a clinically useful correlation with prognosis.