Inflammation and prognosis in colorectal cancer.
ABSTRACT Previous work has indicated that quantification of inflammatory cell reaction is of prognostic value in colorectal cancer. We evaluated the prognostic significance of inflammatory cell reaction patterns in colorectal cancer and developed a grading method which could be used in the routine assessment of tumours.
The intensity of overall inflammatory cell reaction, numbers of neutrophilic and eosinophilic granulocytes, lymphoid cells and macrophages in both the central region and the invasive margin were estimated in 386 colorectal cancer patients. Prognostic significance was analysed by uni- and multivariate analysis.
Our method for classification of inflammatory reaction was reliable. High-grade inflammation at the invasive margin in Dukes' stage A and B cancers (pT1-2N0 and pT3N0, respectively) was associated with better 5-year-survival (87.6%) than low-grade inflammation (47.0%).
Inflammatory cell response at the invasive border is a relevant prognostic indicator and could be easily incorporated into the routine evaluation of histopathological specimens.
- SourceAvailable from: Donald C McmillanBritish Journal of Cancer 10/2014; · 5.08 Impact Factor
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ABSTRACT: Purpose: Although tumor infiltrating lymphocytes have been associated with response to neoadjuvant therapy, measurement is typically subjective, semi-quantitative and does not differentiate between subpopulations. Here we describe a quantitative objective method for analyzing lymphocyte subpopulations and assess their predictive value. Methods: We develop a quantitative immunofluorescence (QIF) assay to measure stromal expression of CD3, CD8, and CD20 on one slide. We validate this assay by comparison to flow cytometry on tonsil and assess predictive value in breast cancer on a neoadjuvant cohort (n = 95). Then each marker is tested for prediction of pathologic complete response (pCR) compared to pathologist estimation of percentage lymphocyte infiltrate. Results: Lymphocyte percentage and CD3, CD8, and CD20 proportions were similar between flow cytometry and QIF on tonsil. Pathologist TIL count predicted pCR (p = 0.043, OR: 4.77[1.05-21.6]) despite fair interobserver reproducibility (kappa= 0.393). Stromal AQUA scores for CD3 (p = 0.023, OR: 2.51[1.13-5.57]), CD8 (p = 0.029, OR: 2.00[1.08-3.72]), and CD20 (p = 0.005, OR: 1.80[1.19-2.72]) predicted pCR in univariate analysis. CD20 AQUA score predicted pCR (p = 0.019, OR: 5.37[1.32-21.8]) independently of age, size, nuclear grade, nodal status, ER, PR, HER2, and Ki-67, whereas CD3, CD8, and pathologist estimation did not. Conclusions: We have developed and validated an objective, quantitative assay measuring tumor infiltrating lymphocytes in breast cancer. While this work provides analytic validity, future larger studies will be required to prove clinical utility.Clinical Cancer Research 09/2014; · 8.19 Impact Factor
- British Journal of Cancer 10/2014; · 4.82 Impact Factor