Research Group in Molecular Pathology

A.    Human Papilloma Virus (HPV).

HPV infection is involved in development of cancer in the uterine cervix as well as in vagina and vulva of women. In both sexes, HPV causes cancer in the anal and ear, nose and neck (ENT) regions. Our research projects are partly focused on the pathogenesis of HPV in cervical cancer, and partly on the rising incidence of HPV in ENT cancers. Subprojects:

1. HPV types involved in the progression from initial infection to high-grade cellular lesions in uterine cervix. This is a clinical retrospective follow-up study of about 1000 women in Western Norway, who are under surveillance for equivocal or low-grade cervical lesions.
2. Quality control of HPV testing in women with equivocal or low-grade cervical lesions.
3. HPV types involved in recurrent high-grade cervical lesions, a post-conisation study.
4. HPV types involved in high-grade cervical lesions including cancer. This is a pan-European multicenter study with local REK approval and funding through GlaxoSmithKline.
5. Role of HPV in pathogenesis of oral cancer, especially in back of tongue and pharyngeal tonsillar cancer. In recent years, HPV has surfaced as a major player in the pathogenesis of ENT cancer. Patients with ENT-cancer caused by HPV infection have a better long-term survival after treatment than HPV-negative ENT cancers. This a collaborative research project lead by prof. Aarstad at the ENT Department at Haukeland University Hospital.

 B.    Lymphomas.

Our lymphoma studies are focused on molecular diagnostic parameters in lymphomas, including immunoglobulin clonal rearrangements and other molecular prognostic biomarkers.

Subprojects:

1. Role of immunoglobulin molecular analysis in lymphomas. This study aims to validate current diagnostic approaches and to improve the clinical molecular analysis employed in the diagnosis of lymphoma, including detection of bone marrow affection and early detection of residual disease. This is a PhD project for Ellen Berget, MD.
2. Prognostic molecular biomarkers in lymphomas, especially in follicular lymphomas.

 C.    Sarcomas.

Sarcomas are a diverse group of malign spindle cell tumors that sometimes also affect children. In these tumors, very distinct molecular genetic aberrations occur that are important for diagnosis, prognosis and treatment options. Subprojects:

1. Molecular analysis in lipomas, atypical lipomas, and liposarcomas. This is a quality assurance study to improve the molecular diagnosis, obtaining better discrimination of benign from low-grade and high-grade lipomatous soft tissue tumors.
2. Mutational analysis in gastro-intestinal stromal tumors (GISTs). Over the past few years a number of activating gene mutations have been discovered in the KIT and PDGFB genes. New treatment strategies have become available in which the response to therapy depends on the type of mutations involved.

D. Non-small cell lung cancer.

1. Haugland HK, Jebsen NL, Mannelqvist M, Skar R, Eide J, Øvrebø K, Horn A, Jensen DK, Monge OR, Lilleng PK. Treatment of patients with gastrointestinal stromal tumour with imatinib mesylate. [Norwegian]. Tidsskrift for Den norske legeforening 2005; 125: 868-72.
   
    
2. Costea DE, Kulasekara KK, E. Neppelberg,  Johannessen AC, Vintermyr OK.Species-specific  fibroblasts required for triggering invasiveness of partially transformed oral keratinocytes. Am. J. Pathol. 2006; 168: 1889-97.
   
    
3. Steigen SE, Bjerkehagen B, Haugland HK, Nordrum IS, Løberg EM, Isaksen V, Eide TJ, Nielsen TO. Diagnostic and prognostic markers for gastrointestinal stromal tumors in Norway. Mod. Pathol. 2008; 21: 46-53.
   
    
4. Lukandu O, Costea DE, Neppelberg E, Johannessen AC, Vintermyr OK. Khat (Catha edulis) induces reactive oxygen species and apoptosis in normal human oral keratinocytes and fibroblasts. Toxicological Sci. 2008; 103: 311-324.
   
    
5. Vintermyr OK, Skar R, Iversen OE, Haugland HK. Usefulness of HPV test on cell sample from the cervix. [Norwegian]. Tidsskrift for Den norske legeforening 2008; 128: 171-173.
   
    
6. Kalungi S, Steine SJ, Wabinga H, Bostad L, Molven A. pRb2/p130 protein expression and RBL2 mutation analysis in Burkitt lymphoma from Uganda. BMC Clin. Path. 2009; 9: 6 (1-7).
   
    
7. Kalungi S, Wabinga H, Molven A, Bostad L. Lymphomas diagnosed in Uganda during the HIV/AIDS pandemic. East Afr. Med. J. 2009; 86: 226-32.
   
    
8. Mangseth K, Helgeland L, Klos J, Molven A, Vintermyr OK. Improved diagnostic segregation of mantle cell lymphoma by determination of cyclin D1/D3 expression ratio in formalin-fixed tissue. Diagn. Mol. Pathol. 2009; 18: 150-5.
   
    
9. Berget E, Helgeland L, Molven A, Vintermyr OK. Detection of clonality in follicular lymphoma using formalin fixed, paraffin embedded tissue samples and BIOMED-2 immunoglobulin primers. J. Clin. Path. 2011; 64: 37-41.
   
    
10. Haugland HK, Casati B, Dørum LM, Bjugn R. Template reporting matters--a nationwide study on histopathology reporting on colorectal carcinoma resections. Hum. Pathol. 2011; 42: 36-40.
    
     
11. Revheim ME, Hole KH, Bruland OS, Haugland HK, Hall KS, Seierstad T. DW MRI for evaluation of treatment response to imatinib in a rectal gastrointestinal stromal tumour. Acta Oncol. 2011; 50: 148-50.
    
     
12. Trønnes H, Haugland HK, Békássy AN, Helle SI, Sorbye H. Small cell lung cancer in a 14-year-old girl. J. Pediatr. Hematol. Oncol. 2012; 34: e86-8.
    
     
13. Søreide K, Sandvik OM, Søreide JA, Gudlaugsson E, Mangseth K, Haugland HK. Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib naïve adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: relation to tumour-biological risk-profile and long-term outcome. Clin. Transl. Oncol. 2012; 14: 619-29.
    
     
14. Brustugun OT, Helland Å, Fjellbirkeland L, Kleinberg L, Ariansen S, Jebsen P, Scott H, Dønnem T, Bremnes R, Berg T, Grønberg BH, Dai HY, Wahl SG, Mangseth K, Helgeland L. Mutation testing for non-small-cell lung cancer. [Norwegian]. Tidsskrift for Den norske legeforening 2012; 132: 952-5.
    
     
15. Berget E, Helgeland L, Lehmann AK, Smievoll AI, Vintermyr OK, Mørk SJ. Primary diffuse large B-cell lymphoma of the dura without systemic recurrence after diagnosis and successful therapy. Acta Oncol. 2013; 52: 1047-9.
    
     
16. Talasila KM, Soentgerath A, Euskirchen P, Rosland GV, Wang J, Huszthy PC, Prestegarden L, Skaftnesmo KO, Sakariassen PO, Eskilsson E, Stieber D, Keunen O, Brekka N, Moen I, Nigro JM, Vintermyr OK, Lund-Johansen M, Niclou S, Mørk SJ, Enger PO, Bjerkvig R, Miletic H. EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis.Acta Neuropathol. 2013; 125: 683-98.
    
     
17. Bredholt T, Ersvær E, Erikstein BS, Sulen A, Reikvam H, Aarstad HJ, Johannessen AC, Vintermyr OK, Bruserud Ø, Gjertsen BT. Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine. BMC Pharmacol. Toxicol. 2013, 11;14:35.
    
     
18. Talasila KM, Brekka N, Mangseth K, Stieber D, Evensen L, Rosland GV, Torsvik A, Wagner M, Niclou SP, Mahesparan R, Vintermyr OK, Bjerkvig R, Nigro JM, Miletic H. Tumor versus Stromal Cells in Culture-Survival of the Fittest? PLoS One. 2013 Dec 2;8(12):e81183.
    
     
19. Budal EB, Haugland HK, Skar R, Maehle BO, Bjørge T, Vintermyr OK. HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway. Cancer Med. 2014 (in press).
    
     
20. Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, Cherniack AD, Ambrogio L, Cibulskis K, Bertelsen B, Romero-Cordoba S, Treviño V, Vazquez-Santillan K, Guadarrama AS, Wright AA, Rosenberg MW, Duke F, Kaplan B, Wang R, Nickerson E, Walline HM, Lawrence MS, Stewart C, Carter SL, McKenna A, Rodriguez-Sanchez IP, Espinosa-Castilla M, Woie K, Bjorge L, Wik E, Halle MK, Hoivik EA, Krakstad C, Gabiño NB, Gómez-Macías GS, Valdez-Chapa LD, Garza-Rodríguez ML, Maytorena G, Vazquez J, Rodea C, Cravioto A, Cortes ML, Greulich H, Crum CP, Neuberg DS, Hidalgo-Miranda A, Escareno CR, Akslen LA, Carey TE, Vintermyr OK, Gabriel SB, Barrera-Saldaña HA, Melendez-Zajgla J, Getz G, Salvesen HB, Meyerson M. Landscape of genomic alterations in cervical carcinomas. Nature. 2014 (in press).