Publications by authors named "P Smickova"

4 Publications

  • Page 1 of 1

LC3A positive "stone like structures" are differentially associated with survival outcomes and CD68 macrophage infiltration in patients with lung adenocarcinoma and squamous cell carcinoma.

Lung Cancer 2021 06 15;156:129-135. Epub 2021 Apr 15.

Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine and Dentistry, Palacký University, Olomouc, Czech Republic; Faculty of Medicine, University of Ostrava, Czech Republic. Electronic address:

Aims: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression.

Methods: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides.

Results: LC3A positive SLSs, were significantly associated with worse overall (OS) and disease-free survival (DFS) outcomes in patients with lung adenocarcinoma (LADC) (HR = 2.4, 95 %CI(.994-1.008, p = 0.029) and HR = 3.9, 95 %CI (1.002-1.014), p = 0.002 respectively), whilst it was associated with better OS and DFS in patients with lung squamous cell carcinoma (LUSC), with marginal significance (HR = .99, 95 %CI(.975-1.011),p = 0.042 and HR = .99, 95 %CI (.975-1.008), p = 0.026). Multivariate analysis showed that LC3A SLSs are independent poor prognostic factor only in patients with LADC. In addition, LC3A SLSs, were negatively associated with CD68 count in LADC, whilst there was a positive correlation in LSCC.

Conclusions: LC3A SLSs are differentially associated with the survival outcomes and CD68 count in LADC and LSCC. Further studies are justified for the understanding the underlying biological mechanisms of this phenomenon.
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http://dx.doi.org/10.1016/j.lungcan.2021.04.008DOI Listing
June 2021

Prognostic value of tumor-infiltrating lymphocytes (TILs) and their association with PD-L1 expression and DNA repair protein RAD51 in patients with resected non-small cell lung carcinoma.

Lung Cancer 2020 09 23;147:30-38. Epub 2020 Jun 23.

Department of Medical Oncology and Hematology, Cantonal Hospital, CH-9007, St. Gallen, Switzerland.

Objectives: DNA repair proteins have emerged as potential predictors for immunotherapy response alongside PD-L1 expression, tumor-infiltrating lymphocytes (TILs) and tumor mutational burden. We analyzed expression of PD-L1, TILs count and expression of the homologous recombination (HR) protein RAD51, as potential prognostic factors in patients with resected non-small-cell lung carcinoma (NSCLC).

Materials And Methods: Discovery set included 96 NSCLC patients from the University Hospital Olomouc (Czech Republic) and a replication set included 1109 NSCLC patients from University Hospital Zurich (Switzerland). Tissue microarrays (TMAs) were stained using the automated staining platform Ventana Benchmark Ultra with antibodies against RAD51,CD3, CD8, CD68 and PD-L1.

Results: Loss of nuclear RAD51 protein was associated with high TILs (r=-0.25, p = 0.01) and PD-L1 status (10.6 vs. 2.4 %, p = 0.012) in patients receiving neoadjuvant chemo-/radiotherapy (CT/RT). In silico analysis from the TCGA data set showed a negative relationship between RAD51 mRNA expression and CD45 (r = ‒0.422, p < 0.0001), CD68 (r = ‒0.326, p < 0.001), CD3 (r = ‒0.266, p < 0.001) and CD8 (r = ‒0.102, p < 0.001). RAD51 low/PD-L1 high patients were clustered as separate entity in the replication set and in TCGA dataset. High TILs status was significantly associated with improved OS in the replication set (unadjusted HR = 0.57, 95 % CI 0.42-0.76, p < 0.001). Similar results have been seen for CD3, CD8 and CD68.

Conclusions: In conclusion, RAD51 nuclear loss is weakly associated with increased TILs and high PD-L1 at the time of surgery in curatively resected NSCLC and after prior exposure to neoadjuvant chemo- or radiotherapy. Both high TILs and RAD51 nuclear loss were confirmed as independent prognostic factors in curatively resected NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2020.06.025DOI Listing
September 2020

Sphingosine kinase-1 predicts overall survival outcomes in non-small cell lung cancer patients treated with carboplatin and navelbine.

Oncol Lett 2019 Aug 7;18(2):1259-1266. Epub 2019 Jun 7.

Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, 77515 Olomouc, Czech Republic.

Sphingosine 1-phosphate (S1P) is a bioactive lipid metabolite associated with cancer cell proliferation, survival, migration and regulation of tumor angiogenesis in various cellular and animal models. Sphingosine kinase-1 (SphK1) and S1P lyase are the main enzymes that respectively control the synthesis and degradation of S1P. The present study analyzed the prognostic and predictive value of SphK1 and S1P lyase expression in patients with non-small cell lung cancer (NSCLC), treated with either surgery alone or in combination with adjuvant carboplatin and navelbine. Formalin-fixed, paraffin-embedded tissue samples from 176 patients with NSCLC were stained immunohistochemically using antibodies against SphK1 and S1P lyase, and their expression was correlated with all available clinicopathological factors. Increased expression of SphK1 was significantly associated with shorter overall and disease free survival in patients treated with adjuvant platinum-based chemotherapy. No prognostic relevance for S1P lyase expression was observed. Collectively, the results suggest that the immunohistochemical detection of SphK1 may be a promising predictive marker in NSCLC patients treated with adjuvant platinum-based chemotherapy.
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http://dx.doi.org/10.3892/ol.2019.10447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607215PMC
August 2019

Tumor autophagy is associated with survival outcomes in patients with resected non-small cell lung cancer.

Lung Cancer 2019 03 8;129:85-91. Epub 2019 Jan 8.

Laboratory of Molecular Pathology, Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentristy, Palacký University, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentristy, Palacký University, Olomouc, Czech Republic. Electronic address:

Objectives: LC3A protein is associated with autophagosomes, and LC3A immunohistochemistry (IHC) is used for the detection of autophagy activity. The aim of this study was to assess the prognostic value of LC3A expression in patients with resected non-small cell lung cancer (NSCLC).

Materials And Methods: We used tissue microarrays (TMAs) constructed from 116 resected stage IB-III NSCLC patients. Standard immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue sections using antibody against LC3A autophagic potein. Stained slides were scanned by Olympus dotSlide Digital Virtual Microscopy System (Japan) and the LC3A staining was evaluated digitally. Groups were compared using the Mann Whitney U test, and correlations were assessed using Spearman's rank test. Survival was calculated using Kaplan-Meier analysis. Primary study endpoint was overall survival (OS), secondardy study endpoint disease-free survival (DFS). Cut-off optimization for LC3A prognostic value was performed using the "cut-off finder' 'software (Charite, Berlin, Germany). In addition, the Kaplan Meier plotter (KmPlot) was used to assess the relationship between LC3A mRNA expression and clinical outcome (OS and DFS) in patients with NSCLC.

Results: From 116 patients, 88 tissue samples were available for final examination. No significant association was found between LC3A staining and other clinicopathological variables, including tumor grade, stage and histological subtype. A higher number of LC3A stone-like structures (SLSs) (>20), was significanly associated with poor OS (HR = 2.27, p = 0.011) and DFS (HR = 2.27, p = 0.003). A significant association between high LC3A mRNA and both a worse OS and worse DFS was found by KMPlot analysis in patients with stage I-III NSCLC.

Conslusion: This retrospective study suggests that SLSs as assessed by LC3A IHC as well as LC3A mRNA expression has a clinically relevant negative prognostic value in patients with resected NSCLC, and should be further investigated.
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http://dx.doi.org/10.1016/j.lungcan.2019.01.001DOI Listing
March 2019
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