ABSTRACT
BACKGROUND/AIM: The aim of the present study was the evaluation of the influence of cancer stem cells and other parameters in stage IV colorectal cancer patients. MATERIALS AND METHODS: One hundred patients were retrospectively included in the study and 24 variables were examined for their relation with response to treatment and survival. RESULTS: A low ploidy score in the histology of colorectal cancer was associated with improvement of performance status and response to therapy. No significant correlations between the percentage of cancer stem cells from the same tissue and the remaining clinical parameters was revealed. In the multivariate analysis of all the examined parameters in Cox models, independent unfavorable prognostic factors were increased ploidy score, existence of bone metastases, use of epoetin, and existence of side-effects such as anorexia, mucositis, and weight loss. CONCLUSION: Our findings emphasize on the prognostic role of ploidy in advanced colorectal cancer, but further analysis is required to evaluate the role of cancer stem cells.
Subject(s)
Colorectal Neoplasms/pathology , Neoplastic Stem Cells/pathology , Ploidies , Prognosis , Adult , Aged , Anorexia/etiology , Anorexia/pathology , Colorectal Neoplasms/complications , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Female , Flow Cytometry , Humans , Male , Middle Aged , Mucositis/etiology , Mucositis/pathology , Neoplasm Metastasis , Neoplasm Staging , Proportional Hazards Models , Weight Loss/geneticsABSTRACT
Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Mutation/genetics , Proto-Oncogene Proteins B-raf/genetics , Class I Phosphatidylinositol 3-Kinases , Female , Humans , Male , Middle Aged , Neoplasm Staging , Phosphatidylinositol 3-Kinases/genetics , Prognosis , Proto-Oncogene Proteins p21(ras)/genetics , Retrospective StudiesABSTRACT
OBJECTIVE: To identify changes in peripheral immune responses in patients with metastatic colorectal cancer (mCRC) treated with irinotecan/5-fluorouracil/leucovorin (IFL) alone or in combination with cetuximab (C-IFL). METHODS: Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (n = 20) and patients with mCRC receiving treatment with either IFL (n = 30) or C-IFL (n = 30) were tested for cytokine production upon polyclonal stimulation with anti-CD3 monoclonal antibody, T cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR) and T regulatory cell (Treg) frequency. The respective results were evaluated over two treatment cycles and further assessed in relation to response to treatment. RESULTS: PBMCs prior to treatment exhibited significantly lower production of IL-2, IFN-γ, IL-12 and IL-18 cytokines and lower auto-MLR responses, whereas Treg frequency, IL-4, IL-10 cytokines were increased compared to healthy donors. During treatment, IL-2, IFN-γ, IL-12, IL-18 and auto-MLR responses increased, while Treg frequency and IL-10 secretion decreased significantly compared to the baseline. Responders to treatment exhibited a significantly higher increase in IL-2, IFN-γ, IL-12 and IL-18 production and auto-MLR responses, and higher decrease in IL-4, IL-10 secretion and Treg frequency. Among all patient subgroups analysed, responders to C-IFL demonstrated significantly higher increase in auto-MLR responses, IL-12 and IL-18 secretion and higher decrease in Treg frequency. CONCLUSION: The disturbed immune parameters observed in patients with mCRC at presentation can be significantly improved during treatment with IFL and this effect can be potentiated by the addition of cetuximab. Monitoring of the peripheral immune system function could be used as surrogate marker in predicting treatment-related outcome.