Ropponen KM, Eskelinen MJ, Lipponen PK, Alhava PK, Kosma VMPrognostic value of tumour-infiltrating lymphocytes (TILs) in colorectal cancer. J Pathol 182: 318-324

Department of Pathology and Forensic Medicine, University of Kuopio, Finland.
The Journal of Pathology (Impact Factor: 7.43). 07/1997; 182(3):318-24. DOI: 10.1002/(SICI)1096-9896(199707)182:3<318::AID-PATH862>3.0.CO;2-6
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Clinical follow-up data of 276 colorectal adenocarcinoma patients treated in Kuopio University Hospital between 1976 and 1986 and followed up for a mean of 14 years were analysed. The clinical findings were correlated with tumour-infiltrating lymphocytes (TILs) and with histological and quantitative factors including nuclear parameters and volume-corrected mitotic index. In univariate survival analysis, TNM classification, Dukes' stage, histological grade, and TILs were significant predictors of survival. TNM classification, Dukes' stage, and TILs also predicted recurrence-free survival. In multivariate analysis, TILs were an independent prognostic factor of survival in all cases, as well as in patients with T1-4N0-3M0 and T1-4N1-3M1. TILs also independently predicted recurrence-free survival. TILs can provide important prognostic information in colorectal cancer to be used in evaluating for adjuvant therapy in different tumour stages.

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    • "In recent studies, normalisation of an initial lymphocytopenia in breast cancer patients treated with chemotherapy leads to an increased clinical outcome (Nieto et al, 2004), and an elevated lymphocyte count was significantly associated with prolonged OS in patients with multiple myeloma (Ege et al, 2008). In colorectal cancer patients, tumour-infiltrating lymphocytes have been shown to be independent prognostic factors of survival in all clinical stages (Ropponen et al, 1997). Furthermore, lymphocytosis was found to be significantly associated with increased OS in metastatic colorectal cancer patients (Leitch et al, 2007). "
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    ABSTRACT: Background: Inflammation has a critical role in the pathogenesis and progression of cancer. Recently, the derived neutrophil to lymphocyte ratio (absolute count of neutrophils divided by the absolute white cell count minus the absolute count of neutrophils; dNLR) has been shown to influence clinical outcome in various cancer entities. In this study, we analysed the dNLR with clinical outcome in stage II and III colon cancer patients. Methods: Three-hundred and seventy-two patients with stage II and III colon cancer were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportion analyses were calculated for time to recurrence (TTR) and overall survival (OS). Results: In univariate analysis, the elevated preoperative dNLR was significantly associated with decreased TTR (hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.57–3.6, P<0.001) and remained significant in multivariate analysis. Patients with dNLR >3 had a median TTR of 83 months, and patients with dNLR ⩽3 showed a median TTR of 132 months. In OS analysis, a dNLR >2.2 was significantly associated with decreased OS in univariate (HR 1.85, 95% CI 1.11–3.08, P=0.018) and multivariate analysis. Patients with dNLR >2.2 showed a median OS of 121 months, and patients with dNLR ⩽2.2 had a median OS of 147 months. Conclusion: The dNLR may be an independent prognostic marker for TTR and OS in patients with stage II and III colon cancer. Independent validation of our findings is warranted.
    British Journal of Cancer 07/2013; 109(2). DOI:10.1038/bjc.2013.346 · 4.84 Impact Factor
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    • "In cancer, the host response, like the intra- or peritumoral inflammation reaction or desmoplasia, can predict better prognosis [6-8]. Theoretically, some matrix-degrading proteinases may play a defensive role by supporting the immune/inflammatory response. "
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    ABSTRACT: Background Matrix metalloproteinases (MMPs) play a role in cancer progression by degrading extracellular matrix and basement membranes, assisting in tumour neovascularization and in supporting immune response in cancer. Methods We studied the prognostic value of immunohistochemical expression of MMP-2, MMP-8, and MMP-9 in a series of 619 colorectal cancer patients using tissue microarray specimens. Results Of the samples, 56% were positive for MMP-2, 78% for MMP-8, and 60% for MMP-9. MMP-9 associated with low WHO grade (p < 0.001). In univariate analysis of Dukes’ B tumours, MMP-9 negativity associated with poor survival (p = 0.018), and MMP-9 positivity was an independent prognostic marker in multivariate analysis of these tumours (p = 0.034). Conclusion Negative MMP-9 expression can predict poor prognosis in Dukes’ B colorectal tumours and may prove useful for identifying patients, who should be offered adjuvant treatment.
    BMC Clinical Pathology 12/2012; 12(1):24. DOI:10.1186/1472-6890-12-24
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    • "TILs were less numerous than in early stages (Dukes stages A and B) [21]. Follicular and paracortical hyperplasia in local lymphatic nodes are also an important prognostic factor in colorectal cancer. "
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    ABSTRACT: Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.
    Clinical and Developmental Immunology 11/2011; 2011(2):174149. DOI:10.1155/2011/174149 · 2.93 Impact Factor
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