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The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer
- Source :
- Annals of Surgical Oncology
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 581 Background: Tumour budding is an independent prognostic factor in colorectal cancer and has recently been defined by the International Consensus Conference on Tumour Budding. The aim was to use the ITBCC budding evaluation method to examine relationships between tumour budding, tumour factors, tumour microenvironment, gene expression profiles and survival in patients with primary operable CRC. Methods: Hematoxylin and Eosin (H&E) stained slides of 953 CRC patients, diagnosed between 1997 and 2007 were evaluated for tumour budding according to the ITBCC-criteria. The tumour microenvironment was evaluated using tumour stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumour inflammatory cell infiltrate. Differential gene expression was assessed using TempO-Seq gene expression profiling (BioSpyder Technologies Inc., CA, USA) using the Surrogate+Tox targeted panel (2,733 genes selected for biological diversity, maximal information content, and widespread pathway coverage). Results: High budding (n = 269/ 28%) was significantly associated with TNM stage (P < 0.001), venous invasion (P < 0.001), weak KM grade (P < 0.001), high TSP (P < 0.001) and reduced cancer specific survival (CSS) (HR = 5.04; 95% confidence interval [CI], 3.50-9.51; P < 0.001) and was independent of venous invasion, KM grade, and Ki67 proliferation index. RNA expression analysis was employed using TempO-Seq to determine differential gene expression between tumours with (n = 8) and without budding (n = 18). Three genes were identified as significantly differentially expressed: S100A2 (S100 calcium binding protein A2) was upregulated by 2.9 fold (padj < 0.00001); REG1A (regenerating family member 1 alpha) was downregulated by 4.7 fold (padj < 0.01) and LCN2 (lipocalin 2) was downregulated by 2.2 fold (padj < 0.01). Conclusions: Tumour budding stratifies patients’ survival in primary operable colorectal cancer and associates with differing gene expression profiles and factors of the tumour. Therefore, the ITBCC budding evaluation method should be used to assess tumour budding as supplement the TNM staging system and can help to further subdivide colorectal cancer into new prognostic groups.
- Subjects :
- Male
Oncology
Cancer Research
Prognostic factor
medicine.medical_specialty
Colorectal cancer
03 medical and health sciences
0302 clinical medicine
Tumor budding
Surgical oncology
Internal medicine
Tumor Microenvironment
medicine
Humans
Neoplasm Invasiveness
In patient
Prospective Studies
Stage (cooking)
Survival rate
Aged
Neoplasm Staging
030304 developmental biology
Colorectal Cancer
0303 health sciences
Tumor microenvironment
business.industry
Hazard ratio
Consensus conference
Middle Aged
Prognosis
medicine.disease
Survival Rate
030220 oncology & carcinogenesis
Cancer research
Tumour budding
T-stage
Female
Surgery
Colorectal Neoplasms
business
Subjects
Details
- ISSN :
- 15344681 and 10689265
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Annals of Surgical Oncology
- Accession number :
- edsair.doi.dedup.....05195c3a65f53697573353417f32d2b2