Local Inflammatory Response Can Predict Clinical Outcome in Patients with Curatively Resected Stage-IIB Colon Cancer: An Advanced Methodological Study

Abstract

Purpose

Although local inflammatory response (LIR) is a reliable survival marker in colon cancers (CCs), there is no consensus on its use in daily practice. We investigated the prognostic value of LIR in a highly homogeneous population with a well-designed methodology.

Methods

Eighty stage-IIB CC patients operated between 2002 and 2012 were included in the study. Standardization was investigated for extra-biopsy evaluation methods (magnification, staining, and counting). Model A was used for intra-biopsy evaluation methods (block, section, and focus). So, this study makes important contributions to the standardization of pathological evaluations.

Results

In method 1, the following analyzes showed more successful results for LIR: relationship with prognostic factors [tumour deposits (p=0.017), Crohn’s-like reaction (p=0.019), advanced grade, (p=0.012), positive surgical margin (p=0.019), perineural invasion (p=0.025), mismatch repair proteins-proficiency (p=0.031)], reproducibility of the study (Kappa=0.49–0.73, Intra-class correlation=0.442–0.724), and correlation of estimates (r=0.704). The cut-off value was also quite useful (area of under ROC=0.820 [0.694-0.920]). In univariate analysis, low LIR was related to poor overall survival (OS; p<0.001) and poor relapse-free survival (RFS, p=0.001) . Multivariate analysis confirmed that low LIR is an independent poor survival marker for OS (Hazard Ratio [HR]=1.32 [1.08-1.61, p=0.005) and RFS (HR=1.50 [1.22-1.85], p<0.001).

Conclusions

Our results showed that low LIR had an independent prognostic significance in stage -IIB CCs. We also recommend using model A and method 1 for successful results and standardization.

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Acknowledgements

We would like to thank the members of Kırıkkale University, Department of Pathology and Internal Medicine for their support and participation. All persons who have contributed to the paper approves for publication of this research.

Abbreviations

AJCC: American Joint Cancer Committee,LIR: Local inflammatory response, CC: Colorectal cancer, H&E: Hematoxylin and eosin, HPF: High-power field,SD: Standard deviation, IHC: Immunohistochemistry,CI: Confidence interval, SD: Standard deviation, ICC: Intra-Class Correlation Coefficient, HR: Hazard ratio, K: Kappa, OS: Overall survival, RFS: Relapse-free survival, MSI: Microsatellite instability, MMR: Mismatch repair proteins, Method 1: Using the ‘x20 objektive&IHC&quantitative’, Model A: Using the ‘deeply invasive blocks&hot-spot area&invasive margin’.

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The author is not associated with any organization or financial involvement that has a financial interest in the issue of the material discussed in the article.

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Correspondence to Mehmet Zengin.

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Zengin, M. Local Inflammatory Response Can Predict Clinical Outcome in Patients with Curatively Resected Stage-IIB Colon Cancer: An Advanced Methodological Study. Pathol. Oncol. Res. 26, 1805–1816 (2020). https://doi.org/10.1007/s12253-019-00758-2

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Keywords

  • Local inflammatory response
  • tumour biomarkers
  • colon cancers
  • stage -IIB