• 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, ...
    • Cancer associated fibroblasts in stage I-IIIA NSCLC: Prognostic impact and their correlations with tumor molecular markers 

      Kilvær, Thomas Karsten; Rakaeekhanehkenari, Mehrdad; Hellevik, Turid; Al-Saad, Samer; Paulsen, Erna-Elise; Busund, Lill-Tove; Dønnem, Tom; Martinez, Inigo Zubiavrre (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-08-07)
      Background Cancer Associated Fibroblasts (CAFs) are thought to regulate tumor growth and metastasis. Fibroblast Activating Protein 1 (FAP-1) is a marker for fibroblast activation and by many recognized as the main marker of CAFs. Alpha Smooth Muscle Actin (α-SMA) is a general myofibroblast marker, and can be used to identify CAFs. This study investigates the prognostic impact of FAP-1 and α-SMA ...
    • CD45RO+ Memory T Lymphocytes – a Candidate Marker for TNM-Immunoscore in Squamous Non-Small Cell Lung Cancer 

      Paulsen, Erna-Elise; Kilvær, Thomas Karsten; Rakaeekhanehkenari, Mehrdad; Johansen Maurseth, Ramona; Al-Saad, Samer; Hald, Sigurd; Al-Shibli, Khalid; Andersen, Sigve; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M.; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11)
      Tumor-infiltrating lymphocytes (TILs) are vital in limiting cancer progression and may supplement the TNM classification. CD45RO+ memory TILs show major prognostic impact in various malignancies but have not been extensively explored in non–small cell lung cancer (NSCLC). In this study, we aimed to evaluate their potential in a NSCLC TNM-Immunoscore. Tissue microarrays were constructed from tumor ...
    • 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) ...
    • Fibroblast growth factor 2 orchestrates angiogenic networking in non-GIST STS patients 

      Kilvær, Thomas Karsten; Valkov, Andrey Yurjevich; Sørbye, Sveinung Wergeland; Smeland, Eivind; Bremnes, Roy M.; Busund, Lill-Tove; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      Non-gastrointestinal stromal tumor soft-tissue sarcomas (non-GIST STSs) constitute a heterogeneous group of tumors with poor prognosis. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor-1 (FGFR-1), in close interplay with platelet-derived growth factor-B (PDGF-B) and vascular endothelial growth factor receptor-3 (VEGFR-3), are strongly involved in angiogenesis. This study ...
    • A gender specific improved survival related to stromal miR-143 and miR-145 expression in non-small cell lung cancer 

      Skjefstad, Kaja Konstanse; Johannessen, Charles; Grindstad, Thea K.W.; Kilvær, Thomas Karsten; Paulsen, Erna Elise; Pedersen, Mona Irene; Dønnem, Tom; Andersen, Sigve; Bremnes, Roy M.; Richardsen, Elin; Al-Saad, Samer; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-04)
      Micro RNAs (miRNA) are small non-coding RNAs that post-transcriptionally regulate gene expression. Dysregulation of miRNA cluster 143/145 has been reported in several malignancies, but their role in non-small cell lung cancer (NSCLC) remains elusive. This study investigates the prognostic impact of miR-143 and miR-145 in primary tumors and metastatic lymph nodes in NSCLC tissue. Tissue from 553 ...
    • High expression of CD20+ lymphocytes in soft tissue sarcomas is a positive prognostic indicator 

      Sørbye, Sveinung Wergeland; Kilvær, Thomas Karsten; Valkov, Andrey Yurjevich; Dønnem, Tom; Smeland, Eivind; Al-Shibli, Khalid Ibrahim; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel, 2012)
      The immune status is important in cancer patients. Tissue microarrays from 249 patients with soft tissue sarcomas were constructed. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+, CD20+ and CD45+ lymphocytes in tumors. High density of CD20+ lymphocytes is an independent positive prognostic indicator for these patients.
    • High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I–III Colon Cancer 

      Selven, Hallgeir; Rasmussen Busund, Lill-Tove; Andersen, Sigve; Pedersen, Mona Irene; Lombardi, Ana Paola Giometti; Kilvær, Thomas Karsten (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-02-24)
      Colon cancer is a common malignancy and a major contributor to human morbidity and mortality. In this study, we explore the expression and prognostic impact of IRS-1, IRS-2, RUNx3, and SMAD4 in colon cancer. Furthermore, we elucidate their correlations with miRs 126, 17-5p, and 20a-5p, which are identified as potential regulators of these proteins. Tumor tissue from 452 patients operated for stage ...
    • High expression of microRNA‑126 relates to favorable prognosis for colon cancer patients 

      Selven, Hallgeir; Rasmussen Busund, Lill-Tove; Bremnes, Roy M.; Andersen, Sigve; Kilvær, Thomas Karsten (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-05)
      miR-126 has been identified both as a tumor suppressor and an oncogene in different types of cancer. The aim of this study was to investigate the prognostic impact of miR-126-expression in colon cancer patients. Tumor tissue from 452 patients operated for stage I–III colon cancer was retrospectively collected and tissue microarrays were constructed. miR-126 expression was evaluated by in situ ...
    • High expression of miR-17-5p and miR-20a-5p predicts favorable disease-specific survival in stage I-III colon cancer 

      Selven, Hallgeir; Kilvær, Thomas Karsten; Andersen, Sigve; Rasmussen Busund, Lill-Tove; Pedersen, Mona Irene; Lombardi, Ana Paola (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-30)
      In many types of cancer, microRNAs (miRs) are aberrantly expressed. The aim of this study was to explore the prognostic impact of miR-17-5p and miR-20a-5p in colon cancer. Tumor tissue from 452 stage I-III colon cancer patients was retrospectively collected and tissue microarrays constructed. miR-17-5p and miR-20a-5p expression was evaluated by in situ hybridization and analyzed using digital ...
    • 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 ...
    • 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 ...
    • Lymphangiogenic Markers and Their Impact on Nodal Metastasis and Survival in Non-Small Cell Lung Cancer--A Structured Review with Meta-Analysis. 

      Kilvær, Thomas Karsten; Paulsen, Erna-Elise; Hald, Sigurd; Wilsgaard, Tom; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-08-25)
      Background In non-small cell lung cancer (NSCLC), nodal metastasis is an adverse prognostic factor. Several mediating factors have been implied in the development of nodal metastases and investigated for predictive and prognostic properties in NSCLC. However, study results differ. In this structured review and meta-analysis we explore the published literature on commonly recognized pathways for ...
    • 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: ...
    • 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. ...
    • Profiling of VEGFs and VEGFRs as prognostic factors in soft tissue sarcoma: VEGFR-3 is an independent predictor of poor prognosis 

      Smeland, E; Kilvær, Thomas Karsten; Valkov, Andrey Yurjevich; Sørbye, Sveinung Wergeland; Bremnes, Roy M.; Busund, Lill-Tove Rasmussen; Dønnem, Tom (Journal article; Tidsskriftartikkel; Peer reviewed, 2010)
    • Prognostic effect of intratumoral neutrophils across histological subtypes of non-small cell lung cancer 

      Rakaee, Mehrdad; Busund, Lill-Tove; Paulsen, Erna-Elise; Richardsen, Elin; Al-Saad, Samer; Andersen, Sigve; Dønnem, Tom; Bremnes, Roy M.; Kilvær, Thomas Karsten (Journal article; Tidsskriftartikkel; Peer reviewed, 2016)
      Recent data indicate that tumor-associated neutrophils (TANs) serve a dual role in tumor progression and regression. CD66b is a neutrophil marker and has been associated with patient outcome in various cancers. However, its clinical impact in non-small cell lung cancer (NSCLC) remains controversial. 536 NSCLC patients, of which 172 harbored lymph node metastases, were included in this study. Tissue ...
    • The prognostic impact of Akt isoforms, PI3K and PTEN related to female steroid hormone receptors in soft tissue sarcomas 

      Valkov, Andrey Yurjevich; Kilvær, Thomas Karsten; Sørbye, Sveinung Wergeland; Dønnem, Tom; Smeland, Eivind; Bremnes, Roy M.; Busund, Lill-Tove (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)
      The PI3K/Akt pathway is involved in cellular survival pathways by inhibiting apoptotic processes and stimulating cell growth and proliferation. Its negative prognostic value has been proven in many types of cancer. In soft tissue sarcomas, the expression profiles of the PI3K/Akt pathway components are poorly defined and their significance uncertain. We aimed to investigate the prognostic impact of ...