Tumor budding in colorectal adenocarcinomas
Since the introduction of the term ‘tumor budding’ in colorectal cancer, this phenomenon has been linked to epithelial-mesenchymal transition (EMT) and has hence suggested to be a fundamental mechanism for epithelial cells to acquire a “malignant” phenotype. Tumor buds are defined as the presence of single tumor cells or small groups of up to four tumor cells at the invasive tumor front (peri-tumoral budding; PTB) or within the main tumor body (intra-tumoral buds; ITB).
Tumor budding is an important additional prognostic factor for patients with colorectal cancer (CRC) and has been linked to adverse outcome in at least three clinical groups of patients: 1) In early CRC (pT1) as a risk factor for lymph node metastasis, 2) In stage II CRC, as an adverse prognostic indicator, and 3) In pre-operative biopsies from rectal cancers, as a help to identify high-risk patients, that may benefit from neo-adjuvant treatment. However, lack of consensus guidelines for standardized assessment has limited the reporting and implementation in daily diagnostic practice.
To hopefully overcome these obstacles an International Tumor Budding Consensus Conference (ITBCC) 2016 took place in Bern, Switzerland in April 2016. Participants included 24 international experts in colorectal cancer pathology and tumor budding with representation across Europe, Asia and North America. The conference succeeded in achieving an international consensus on the definition of tumor budding, the prognostic importance of tumor budding, and established universally accepted criteria for tumor budding assessment and recommendations for routine pathology reporting. The guidelines were presented at the European Society of Pathology Congress in Cologne, September 2016 and will be published in a peer-reviewed journal in 2017.
Assessment of tumor budding is primarily performed on H&E stained sections due to the larger amount of published data on the prognostic and predictive value, currently based on H&E. However, working groups have been established to collect data on the value of immunohistochemistry and digitalization and image analysis in this field.
The presentation will include the basis for the current guidelines, as well as the ongoing work on immunohistochemistry and digitalization and image analysis.
Tine Plato Hansen was board-certified as a specialist in pathology in 2005 and is a senior consultant at the Department of Pathology, Herlev Hospital, Copenhagen, Denmark since January 2017. She is also an assistant professor at the University of Copenhagen since 2014. Before that she held similar positions at Hvidovre Hospital, Copenhagen, at Odense University Hospital, and at the University of Southern Denmark. Scientifically, her main clinical expertise and interest is gastrointestinal pathology, especially colorectal cancer, with a focus on immunohistochemical and molecular prognostic and predictive markers. She is a member of the Scientific Committee of the Danish Colorectal Cancer Group (DCCG) and of the DCCG pathology working group, responsible for the Danish National Guidelines for the diagnosis and treatment of colorectal cancer. In April 2016 she represented the Danish pathologists at the International Tumor Budding Consensus Conference in Bern, Switzerland in April 2016. She is a member of the international working groups on tumor budding.
Tine Plato Hansen is an author and co-author of about 25 peer reviewed scientific papers and more conference abstracts in these fields, as well as being a supervisor on several undergraduate research projects and PhD studies.
Cederbye CN, Palshof JA, Hansen TP, Duun-Henriksen AK, Linnemann D, StenvangJ, Nielsen DL, Brünner N, Viuff BM. Antibody validation and scoring guidelines for ABCG2 immunohistochemical staining in formalin-fixed paraffin-embedded colon cancer tissue. Sci Rep. 2016 Jun 3;6:26997.
Jensen NF, Stenvang J, Beck MK, Hanáková B, Belling KC, Do KN, Viuff B, Nygård SB, Gupta R, Rasmussen MH, Tarpgaard LS, Hansen TP, Budinská E, Pfeiffer P, Bosman F, Tejpar S, Roth A, Delorenzi M, Andersen CL, Rømer MU, Brünner N, Moreira JM. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance. Mol Oncol. 2015 Jun;9(6):1169-85.
Smith DH, Fiehn AM, Fogh L, Christensen IJ, Hansen TP, Stenvang J, Nielsen HJ, Nielsen KV, Hasselby JP, Brünner N, Jensen SS. Measuring ERCC1 protein expression in cancer specimens: validation of a novel antibody. Sci Rep. 2014 Mar 7;4:4313.
Bellon E, Ligtenberg MJ, Tejpar S, Cox K, de Hertogh G, de Stricker K, Edsjö A, Gorgoulis V, Höfler G, Jung A, Kotsinas A, Laurent-Puig P, López-Ríos F, Hansen TP, Rouleau E, Vandenberghe P, van Krieken JJ, Dequeker E. External quality assessment for KRAS testing is needed: setup of a European program and report of the first joined regional quality assessment rounds. 2011;16(4):467-78.