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Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates and appears highly promising as a supplement to the tumor-node-metastasis (TNM) classification of various tumors. In colorectal cancer, an international task force has initiated prospective multicenter studies aiming to implement TNM-Immunoscore (TNM-I) in a routine clinical setting. In breast cancer, recommendations for the evaluation of tumor-infiltrating lymphocytes (TILs) have been proposed by an international working group. Regardless of promising results, there are potential obstacles related to implementing TNM-I into the clinic. Diverse methods may be needed for different malignancies and even within each cancer entity. Nevertheless, a uniform approach across malignancies would be advantageous. In nonsmall-cell lung cancer (NSCLC), there are several previous reports indicating an apparent prognostic importance of TILs, but studies on TILs in a TNM-I setting are sparse and no general recommendations are made. However, recently published data is promising, evoking a realistic hope of a clinical useful NSCLC TNM-I. This review will focus on the TNM-I potential in NSCLC and propose strategies for clinical implementation of a TNM-I in resected NSCLC. [ABSTRACT FROM AUTHOR]

Background: Platelet-derived growth factors (PDGFs) and vascular endothelial growth factors and their receptors [platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs)] are related to both angiogenesis and lymphangiogenesis and are important targets in new cancer treatment strategies. We aimed to study the PDGFs/PDGFRs and correlations with lymph node metastasis (LNM) and investigate the prognostic impact of the co-expression of PDGF-B and VEGFR-3 and its correlation with LNM. Patients and methods: Tumor tissue samples from 335 resected patients with stage I–IIIA non-small-cell lung cancer (NSCLC) were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers PDGF-A, PDGF-B, PDGF-C, PDGF-D, PDGFR-a, PDGFR-b, VEGFR-3 and D2-40. Results: There were 232 N0 and 103 N+ patients (76 N1 and 27 N2). In multivariate analyses, high tumor cell PDGFA expression (P = 0.017) correlated with LNM. Tumor cell co-expression of VEGFR-3 and PDGF-B correlated with nodal metastasis and was an independent indicator of poor prognosis (hazard ratio 4.8, confidence interval 95% 2.80–8.31, P < 0.001). Conclusion: Tumor cell PDGF-A expression correlates with LNM, and the co-expression of PDGF-B and VEGFR-3 is strongly associated with poor survival in NSCLC patients. [ABSTRACT FROM AUTHOR]

Vimentin, nuclear factor-κB (NF-κB) p105, fascin, E-cadherin, TGF-β, Par6 and atypical PKC are molecular markers that play an important role in cell differentiation. Herein, we investigate their prognostic impact in primary non-small-cell carcinoma (NSCLC). Tumour tissue samples from 335 resected patients with stage I–IIIA were used. Tissue microarrays were constructed from duplicate cores of both neoplastic cells and stromal cells and were immunohistochemically evaluated. In univariate analyses, high tumour epithelial cell expressions of NF-κB p105 (P=0.02) and E-cadherin (P=0.03) were positive prognostic indicators for disease-specific survival (DSS), whereas high tumour epithelial cell expression of vimentin (P=0.001) was a negative prognostic indicator. High expression of NF-κB p105 (P=0.001) and Par6 (P=0.0001) in the stromal compartment correlated with a good prognosis. In multivariate analyses, the tumour epithelial cell expression of NF-κB p105 (P=0.0001) and vimentin (P=0.005) and the stromal cell expression of NF-κB p105 (P=0.007) and Par6 (P=0.0001) were independent prognostic factors for DSS. High expression of NF-κB p105 and low expression of vimentin in tumour epithelial cells are independent predictors of better survival in primary NSCLC. In stromal cells, high expressions of NF-κB p105 and Par6 are both favourable independent prognostic indicators.British Journal of Cancer (2008) 99, 1476–1483. doi:10.1038/sj.bjc.6604713 www.bjcancer.com Published online 14 October 2008 [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF, p < 0.001) and clinical failure (CF, p = 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32–2.67, p < 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is a highly heterogenous disease and one of the leading causes of mortality in developed countries. Recently, studies have shown that expression of immune checkpoint proteins are directly or indirectly repressed by microRNAs (miRs) in many types of cancers. The great advantages of using miRs based therapy is the capacity of these short transcripts to target multiple molecules for the same- or different pathways with synergistic immune inhibition effects. miR-424 has previously been described as a biomarker of poor prognosis in different types of cancers. miR-424 is also found to target both the CTLA-4/CD80- and PD-1/PD-L1 axis. In the present study, the clinical significance of miR-424-3p expression in PC tissue was evaluated. Naïve radical prostatectomy specimens from 535 patients was used for tissue microarray construction. In situ hybridization was used to evaluate the expression of miR-424-3p and immunohistochemistry was used for CTLA-4 protein detection. In univariate- and multivariate analyses, low expression of miR-424-3p was significant associated with clinical failure-free survival, (p = 0.004) and p = 0.018 (HR:0.44, CI95% 0.22–0.87). Low expression of miR-424-3p also associated strongly with aggressive phenotype of PC. This highlight the importance of miR-424-3p as potential target for therapeutic treatment in prostate cancer. [ABSTRACT FROM AUTHOR]