• Assessing PDL-1 and PD-1 in NoneSmall Cell Lung Cancer: A Novel Immunoscore Approach 

      Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rakaee, Mehrdad; Al-Saad, Samer; Hald, Sigurd; Andersen, Sigve; Richardsen, Elin; Ness, Nora; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-10-05)
      Novel immune biomarkers could complement the TNM classification for nonesmall cell cancer (NSCLC), improving the prognostic accuracy. The present study evaluated the prognostic significance of the immune checkpoint molecules programmed cell death protein 1 (PD-1) and PD-1 ligand (PD-L1) in 536 patients with stage I to IIIA NSCLC using an Immunoscore approach. Independently, and in combination, ...
    • CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases 

      Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rakaee, Mehrdad; Richardsen, Elin; Hald, Sigurd; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-07-13)
      The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 ...
    • Differential prognostic impact of platelet-derived growth factor receptor Expression in NSCLC 

      Kilvær, Thomas Karsten; Rakaee, Mehrdad; Hellevik, Turid; Vik, Jørg; de Petris, Luigi; Dønnem, Tom; Strell, Carina; Østman, Arne; Busund, Lill-Tove; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-15)
      Preclinical evidence suggests that stromal expression of platelet-derived growth factor receptors (PDGFRs) stimulates tumor development and diminishes intratumoral drug uptake. In non-small cell lung cancer (NSCLC), the clinical relevance of stromal PDGFR expression remains uncertain. Tumor specimens from 553 patients with primary operable stage I-IIIB NSCLC was obtained and tissue micro-arrays (TMA) ...
    • Digitally quantified CD8+ cells: the best candidate marker for an immune cell score in non-small cell lung cancer? 

      Paulsen, Erna-Elise; Andersen, Sigve; Rakaee, Mehrdad; Bremnes, Roy M.; Rasmussen Busund, Lill-Tove; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-10-09)
      The TNM classification is well established as a state-of-the-art prognostic and treatment-decision-making tool for non-small cell lung cancer (NSCLC) patients. However, incorporation of biological data may hone the TNM system. This article focuses on choosing and incorporating subsets of tissue-infiltrating lymphocyte (TIL), detected by specific immunohistochemistry and automatically quantified by ...
    • Estrogen receptors α and β and aromatase as independent predictors for prostate cancer outcome 

      Grindstad, Thea; Skjefstad, Kaja; Andersen, Sigve; Ness, Nora; Nordby, Yngve; Al-Saad, Samer; Fismen, Silje; Dønnem, Tom; Rakaee, Mehrdad; Busund, Lill-Tove; Bremnes, Roy M.; Richardsen, Elin (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-09-09)
      Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Tissue microarrays ...
    • Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort 

      Richardsen, Elin; Andersen, Sigve; Al-Saad, Samer; Rakaee, Mehrdad; Nordby, Yngve; Pedersen, Mona Irene; Ness, Nora; Grindstad, Thea K.W.; Movik, Ingeborg; Dønnem, Tom; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-15)
      The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related ...
    • Evaluation of the proliferation marker Ki-67 in a large prostatectomy cohort. 

      Richardsen, Elin; Andersen, Sigve; Al-Saad, Samer; Rakaee, Mehrdad; Nordby, Yngve; Pedersen, Mona Irene; Ness, Nora; Grindstad, Thea K.W.; Movik, Ingeborg; Dønnem, Tom; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-15)
      The tumor proliferation index marker Ki-67 is strongly associated with tumor cell proliferation, growth and progression, and is widely used in routine clinicopathological investigation. Prostate cancer is a complex multifaceted and biologically heterogeneous disease, and overtreatment of localized, low volume indolent tumors, is evident. Here, we aimed to assess Ki-67 expression and related ...
    • Expression of phosphatase of regenerating liver (PRL)-3, is independently associated with biochemical failure, clinical failure and death in prostate cancer 

      Andersen, Sigve; Richardsen, Elin; Rakaee, Mehrdad; Bertilsson, Helena; Bremnes, Roy; Børset, Magne; Busund, Lill-Tove; Slørdahl, Tobias (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-11-30)
      Background: Prostate cancer (PC) stratification needs new prognostic tools to reduce overtreatment. Phosphatase of regenerating liver (PRL-3) is a phosphatase found at high levels in several cancer types, where its expression is associated with survival. A recent PC cell line study has shown it to be involved in PC growth and migration. <br>Methods: We used a monoclonal antibody to evaluate ...
    • High expression of miR-17-5p in tumor epithelium is a predictor for poor prognosis for prostate cancer patients 

      Støen, Maria Jenvin; Andersen, Sigve; Rakaee, Mehrdad; Pedersen, Mona Irene; Ingebriktsen, Lise Martine; Bremnes, Roy M.; Dønnem, Tom; Lombardi, Ana Paola; Kilvær, Thomas Karsten; Rasmussen Busund, Lill-Tove; Richardsen, Elin (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-05)
      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 ...
    • High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence 

      Nordby, Yngve; Richardsen, Elin; Rakaee, Mehrdad; Ness, Nora; Dønnem, Tom; Patel, Hitendra R.H.; Busund, Lill-Tove; Bremnes, Roy M.; Andersen, Sigve (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-24)
      Due to a lack of sufficient diagnostic tools to predict aggressive disease, there is a significant overtreatment of patients with prostate cancer. Platelet derived growth factors (PDGFs) and their receptors (PDGFRs) are key regulators of mesenchymal cells in the tumor microenvironment, and has been associated with unfavorable outcome in several other cancers. Herein, we aimed to investigate the ...
    • Immune Infiltration and Clinical Outcome in Non-Small Cell Lung Cancer 

      Rakaee, Mehrdad (Doctoral thesis; Doktorgradsavhandling, 2019-03-12)
      Lung cancer is the cancer responsible for the most deaths worldwide. Treatment is multimodal and based on information specific to the tumor (histology, stage, biology and genetics aberrations) and patient-related factors. During the last decade, the arrival of novel targeted therapies and immunotherapy, has led to a paradigm shift in the management of lung cancer. In this regard, assessment of tumor ...
    • The impact of MET, IGF-1, IGF1R expression and EGFR mutations on survival of patients with non-small-cell lung cancer 

      Al-Saad, Samer; Richardsen, Elin; Kilvær, Thomas Karsten; Dønnem, Tom; Andersen, Sigve; Rakaee, Mehrdad; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-07-25)
      Introduction: <br> To compare the efficacy of silver in situ hybridization (SISH) and immunohistochemistry (IHC) in detecting MET and IGF1R alterations and to investigate their prevalence and prognostic significance. A possible correlation between MET receptor expression, MET gene alterations and the two most frequent occurring EGFR gene mutations was also investigated. <br>Materials and ...
    • Impact of microvessel patterns and immune status in NSCLC: a non-angiogenic vasculature is an independent negative prognostic factor in lung adenocarcinoma 

      Paulsen, Erna-Elise; Andersen, Sigve; Rakaee, Mehrdad; Pedersen, Mona Irene; Lombardi, Ana Paola; Pøhl, Mette; Kilvær, Thomas Karsten; Rasmussen Busund, Lill-Tove; Pezzella, Francesco; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-04-26)
      Introduction: Non-small cell lung carcinomas (NSCLC) exhibit different microvessel patterns (MVPs). Basal (BA), diffuse (DA) and papillary (PA) patterns show signs of angiogenesis (new blood vessels), while an alveolar pattern indicates that tumors are co-opting existing normal vessels (non-angiogenic alveolar, NAA). NAA tumor growth is known to exist in NSCLC, but little is known about its prognostic ...
    • Interplay of immune and kidney resident cells in the formation of tertiary lymphoid structures in lupus nephritis 

      Jamaly, Simin; Rakaee, Mehrdad; Abdi, Reza; tsokos, George; Fenton, Kristin Andreassen (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-27)
      Kidney involvement confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis (LN) involves diverse mechanisms instigated by elements of the autoimmune response which alter the biology of kidney resident cells. Processes in the glomeruli and in the interstitium may proceed independently albeit crosstalk between the two is ...
    • Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer 

      Richardsen, Elin; Andersen, Sigve; Al-Saad, Samer; Rakaee, Mehrdad; Nordby, Yngve; Pedersen, Mona Irene; Ness, Nora; Ingebriktsen, Lise; Fassina, Ambrogio; Tasken, Kristin Austlid; Millls, Ian; Dønnem, Tom; Bremnes, Roy M.; Rasmussen Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-23)
      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 ...
    • Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial 

      Rakaee, Mehrdad; Andersen, S.; Giannikou, K.; Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rasmussen Busund, Lill-Tove; Berg, Thomas; Richardsen, Elin; Lombardi, Ana Paola; Adib, E.; Pedersen, Mona Irene; Tafavvoghi, Masoud; Wahl, Sissel Gyrid Freim; Petersen, R.H.; Bondgaard, A.L.; Yde, C.W.; Baudet, C.; Licht, P.; Lund-Iversen, Marius; Grønberg, Bjørn Henning; Fjellbirkeland, Lars; Helland, Åslaug; Pøhl, M.; Kwiatkowski, D.J.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-04-24)
      Background - We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail.<p> <p>Patients and methods - We developed a machine learning (ML)-based model to classify tumors into one of three categories: ...
    • MicroRNA 141 is associated to outcome and aggressive tumor characteristics in prostate cancer 

      Richardsen, Elin; Andersen, Sigve; Melbø-Jørgensen, Christian; Rakaee, Mehrdad; Ness, Nora; Al-Saad, Samer; Nordby, Yngve; Pedersen, Mona Irene; Dønnem, Tom; Bremnes, Roy M.; Rasmussen Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-01-23)
      A large number of miRNAs influence key cellular processes involved in prostate tumorigenesis. Previous studies have demonstrated high expression of miRNAs in human prostate cancer (PC) tissues and cell lines. In previous microarray data, we found miR-141 to be upregulated and miR-145 to be downregulated in PC. In this large PC cohort (n = 535), we explored the prognostic role of miR-141 and miR-145 ...
    • Overexpression of miR-20a-5p in Tumor Epithelium Is an Independent Negative Prognostic Indicator in Prostate Cancer — A Multi-Institutional Study 

      Stoen, Maria J.; Andersen, Sigve; Rakaee, Mehrdad; Pedersen, Mona I.; Ingebriktsen, Lise M.; Donnem, Tom; Lombardi, Ana P. G.; Kilvaer, Thomas K.; Busund, Lill-Tove R.; Richardsen, Elin (Master thesis; Mastergradsoppgave; Journal article; Tidsskriftartikkel; Peer reviewed, 2022-10-26)
      <p><i>Background:</i> MicroRNAs (miRs) have critical regulatory roles in cell functions, and are involved in prostate cancer tumorigenesis. miR-20a-5p is a member of the oncogenic miR-17-92 cluster. Overexpressed miR-20a-5p has been shown to increase both cell proliferation and cell migration in cancers. The aim of our cohort study was to evaluate the prognostic role of miR-20a-5p in prostate cancer. ...
    • Overexpression of mir-20a-5p in tumor epithelium is an independent negative prognostic indicator in prostate cancer—a multi-institutional study 

      Stoen, Maria J.; Andersen, Sigve; Rakaee, Mehrdad; Pedersen, Mona I.; Ingebriktsen, Lise M.; Dønnem, Tom; Lombardi, Ana P. G.; Kilvaer, Thomas K.; Rasmussen Busund, Lill-Tove; Richardsen, Elin (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-08-14)
      <i>Objective</i>: assessing the prognostic role of miR-20a-5p, in terms of clinical outcome, in a large multi-institutional cohort study.<br><br> <i>Methods</i>: Tissue microarrays from 535 patients’ prostatectomy specimens were constructed. In situ hybridization was performed to assess the expression level of miR-20a-5p in different tissue subregions: tumor stroma (TS) and tumor epithelium (TE). ...
    • The presence of intraepithelial CD45RO+ cells in resected lymph nodes with metastases from NSCLC patients is an independent predictor of disease-specific survival 

      Kilvær, Thomas Karsten; Paulsen, Erna-Elise; Rakaee, Mehrdad; Al-Saad, Samer; Johansen Maurseth, Ramona; Al-Shibli, Khalid; Bremnes, Roy M.; Busund, Lill-Tove; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-04-07)
      background: Operable non-small cell lung cancer (NSCLC) patients whose tumours have spread to regional or central lymph nodes at the time of diagnosis have dismal prognoses compared with those who have limited disease. The current TNM staging system for NSCLC poorly distinguishes patients with lymph-node metastases who will succumb to, and those who will eventually be cured from, their disease. ...