scholarly journals Interobserver Variability in the Assessment of Tumor Budding in pT 3/4 Colon Cancer: Improvement by Supporting Immunohistochemistry?

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 730
Author(s):  
Benedikt Martin ◽  
Patrick Mayr ◽  
Regina Ihringer ◽  
Eva-Maria Schäfer ◽  
Elżbieta Jakubowicz ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Interobserver Variability ◽  
Prognostic Significance ◽  
Distant Metastases ◽  
Consensus Conference ◽  
Tumor Budding ◽  
Cancer Specific Survival ◽  
Cytokeratin Immunohistochemistry ◽  
Different Levels ◽  
Level Of Agreement

The prognostic significance of tumor budding in colon cancer is unequivocally documented, and the recommendations of the International Tumor Budding Consensus Conference (ITBCC) are currently the accepted basis for its assessment. Up to now, it is unknown whether the general use of a supporting cytokeratin immunohistochemistry can improve the interobserver variability and prognostic significance. Six investigators with different levels of experience reassessed 229 cases of colon carcinoma (pT3/4, N+/−, M0) with a supporting cytokeratin immunohistochemistry. The results were compared to previous assessments, which have been performed only on H & E. Bd3 was significantly associated with the occurrence of distant metastases according to the assessments of three out of six investigators (p < 0.05). Only one single investigator reached significant results concerning the cancer specific survival (p = 0.01). The pairwise kappa values range between a poor and moderate level of agreement (range 0.17–0.45; median 0.21). In conclusion, the results show no superiority of the use of an additional cytokeratin immunohistochemistry compared to the conventional analysis on sole H & E slides. Therefore, the general supporting use of a cytokeratin immunohistochemical staining seems to be inadvisable in colon cancer in consideration of necessary resources and costs.

scholarly journals Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients

2021 ◽  
Author(s):  
Fatima El agy ◽  
Sanae El bardai ◽  
Laila Bouguenouch ◽  
Nada Lahmidani ◽  
Mohammed El abkari ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Colon Adenocarcinoma ◽  
Distant Metastases ◽  
Consensus Conference ◽  
Clinicopathological Features ◽  
Molecular Signature ◽  
Tumor Budding ◽  
Prognostic Impact ◽  
Kras Mutations

Abstract Background: Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in the Moroccan population. Methods: We collected data of 100 patients with operated colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by Immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequençing. Results: High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age (P=0.03), presence of perineural invasion (P=0.02), presence of vascular invasion (P=0.05), distant metastases (P˂0.001), advanced TNM stage (P=0.001), the occurrence of relapse (P=0.04), and the high number of deceased cases (P=0.02). Interestingly, we found that tumors with high budding were more likely to be microsatellite stable (MSS) (P=0.005) and harbor more KRAS mutations (P=0.02). In all stages, High tumor budding was correlated with poorer overall survival (P=0.04) and decreased relapse-free survival with a difference close to significance ((P=0.09). we concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. Conclusions: Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.

scholarly journals Stroma AReactive Invasion Front Areas (SARIFA)—A New Easily to Determine Biomarker in Colon Cancer—Results of a Retrospective Study

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4880
Author(s):  
Benedikt Martin ◽  
Bianca Grosser ◽  
Lana Kempkens ◽  
Silvia Miller ◽  
Svenja Bauer ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Tumor Stroma ◽  
Prognostic Indicator ◽  
Tumor Budding ◽  
Cancer Specific Survival ◽  
Invasion Front ◽  
Group A ◽  
Group B

Many studies have used histomorphological features to more precisely predict the prognosis of patients with colon cancer, focusing on tumor budding, poorly differentiated clusters, and the tumor–stroma ratio. Here, we introduce SARIFA: Stroma AReactive Invasion Front Area(s). We defined SARIFA as the direct contact between a tumor gland/tumor cell cluster (≥5 cells) and inconspicuous surrounding adipose tissue in the invasion front. In this retrospective, single-center study, we classified 449 adipose-infiltrative adenocarcinomas (not otherwise specified) from two groups based on SARIFA and found 25% of all tumors to be SARIFA-positive. Kappa values between the two pathologists were good/very good: 0.77 and 0.87. Patients with SARIFA-positive tumors had a significantly shorter colon-cancer-specific survival (p = 0.008, group A), absence of metastasis, and overall survival (p < 0.001, p = 0.003, group B). SARIFA was significantly associated with adverse features such as pT4 stage, lymph node metastasis, tumor budding, and higher tumor grade. Moreover, SARIFA was confirmed as an independent prognostic indicator for colon-cancer-specific survival (p = 0.011, group A). SARIFA assessment was very quick (<1 min). Because of low interobserver variability and good prognostic significance, SARIFA seems to be a promising histomorphological prognostic indicator in adipose-infiltrative adenocarcinomas of the colon. Further studies should validate our results and also determine whether SARIFA is a universal prognostic indicator in solid cancers.

scholarly journals The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer

2019 ◽  
Vol 26 (13) ◽  
pp. 4397-4404 ◽  
Author(s):  
Hester C. van Wyk ◽  
Antonia Roseweir ◽  
Peter Alexander ◽  
James H. Park ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Evaluation Method ◽  
Venous Invasion ◽  
Staging System ◽  
Consensus Conference ◽  
Tumor Budding ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
The Relationship

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC.

scholarly journals Tumor Budding, uPA, and PAI-1 in Colorectal Cancer: Update of a Prospective Study

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Bruno Märkl ◽  
Jochen Hardt ◽  
Simon Franz ◽  
Tina Schaller ◽  
Gerhard Schenkirsch ◽  
...  
Keyword(s):  
Distant Metastases ◽  
Tumor Budding ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Grade ◽  
Cancer Specific Survival ◽  
Tissue Samples ◽  
Colon Cancers ◽  
Validation Set ◽  
A Prospective Study ◽  
Pai 1

Aims. The prognostic role of the proteases uPA and PAI-1, as well as tumor budding, in colon cancer, has been investigated previously.Methods. We provide 6-year follow-up data and results of the validation set. The initial test set and validation set consisted of 55 colon cancers and 68 colorectal cancers, respectively. Tissue samples were analyzed for uPA and PAI-1 using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Tumor budding was analyzed on cytokeratin-stained slides. Survival analyses were performed using cut-offs that were determined previously.Results. uPA was not prognostic for outcome. PAI-1 showed a trend towards reduced cancer specific survival in PAI-1 high-grade cases (68 versus 83 months;P=0.091). The combination of high-grade PAI-1 and tumor budding was associated with significantly reduced cancer specific survival (60 versus 83 months;P=0.021). After pooling the data from both sets, multivariate analyses revealed that the factors pN-stage, V-stage, and a combination of tumor budding and PAI-1 were independently prognostic for the association with distant metastases.Conclusions. A synergistic adverse effect of PAI-1 and tumor budding in uni- and multivariable analyses was found. PAI-1 could serve as a target for anticancer therapy.

Interobserver variability in the H&E-based assessment of tumor budding in pT3/4 colon cancer: does it affect the prognostic relevance?

2018 ◽  
Vol 473 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Benedikt Martin ◽  
Eva Schäfer ◽  
Elzbieta Jakubowicz ◽  
Patrick Mayr ◽  
Regina Ihringer ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Interobserver Variability ◽  
Tumor Budding ◽  
Prognostic Relevance

scholarly journals Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial

2019 ◽  
Vol 37 (22) ◽  
pp. 1886-1894 ◽  
Author(s):  
Hideki Ueno ◽  
Megumi Ishiguro ◽  
Eiji Nakatani ◽  
Toshiaki Ishikawa ◽  
Hiroyuki Uetake ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Model ◽  
Controlled Trial ◽  
Multivariable Analysis ◽  
Consensus Conference ◽  
Stage Ii ◽  
Tumor Budding ◽  
Predictive Values ◽  
Stage Ii Colon Cancer

PURPOSE The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899 ). PATIENTS AND METHODS Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients’ registration. RESULTS Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P < .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum ( P < .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

Prognostic significance of K- ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with dukes C colon cancer

2001 ◽  
Vol 44 (3) ◽  
pp. 358-363 ◽  
Author(s):  
W. A. Bleeker ◽  
V. M. Hayes ◽  
A. Karrenbeld ◽  
R. M. W. Hofstra ◽  
E. Verlind ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Tp53 Mutations ◽  
Dukes C

Prognostic Significance and Correlation with Survival of bcl-2 and TGF-β RII in Colon Cancer

2003 ◽  
Vol 48 (12) ◽  
pp. 2284-2289 ◽  
Author(s):  
Gregory Kouraklis ◽  
John Kakisis ◽  
Stamatios Theoharis ◽  
Antonia Tzonou ◽  
Andromachi Glinavou ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Significance
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