Heikki Joensuu

Helsinki University Central Hospital, Helsinki, Uusimaa, Finland

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Publications (507)3482.36 Total impact

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    ABSTRACT: Metastatic gastrointestinal stromal tumour (GIST) is generally an incurable disease with variable response to imatinib. We aimed to develop prognostic nomograms to predict overall survival (OS) and progression-free survival (PFS) for patients treated with imatinib. Nomograms were developed in a training cohort (n=330) of patients treated in a randomised trial (EORTC-ISG-AGITG 62005 phase III study) using Cox regression models, and validated in patients (n=236) treated in routine clinical care from six referral centres. Nomogram performance was assessed by calculating the c statistic. A classification based on the nomograms' scores was generated to group patients according to risk. Nomogram risk factors for OS and PFS were size of the largest metastasis, tumour genotype, primary tumour mitotic count, haemoglobin and blood neutrophil count at commencement of imatinib. The nomograms predicted survival with a c statistic of 0.75 (training) and 0.62 (validation) for OS, and 0.69 (training) and 0.62 (validation) for PFS. When tested in the validation cohort, the nomograms discriminated well the high and intermediate risk from low risk patients (hazard ratio [HR] for OS 3.83, 95% confidence interval [CI] 1.71-8.56; and 2.48, 95% CI 1.12-5.50; for PFS 2.84, 95% CI 1.66-4.87; and 1.45, 95% CI 0.87-2.41, respectively). The nomograms predicted the risk of GIST progression and death with good discrimination of risk groups, and may be of value for patient counselling and risk stratification. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 03/2015; 51(7). DOI:10.1016/j.ejca.2015.02.015 · 4.82 Impact Factor
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    ABSTRACT: Mutated KIT and platelet-derived growth factor alpha gene (PDGFRA) drive GI stromal tumor (GIST) oncogenesis, but the clinical significance of their single mutations is known incompletely. We identified 11 population-based series of patients with GIST through a literature search and pooled individual data from 3,067 patients treated with macroscopically complete tumor excision. Mutation analysis was done from 1,505 tumors. We analyzed associations between KIT and PDGFRA mutations and recurrence-free survival (RFS) in the subsets in which patients were treated with surgery alone. We identified 301 different single mutations in KIT and 33 in PDGFRA. Patients with PDGFRA mutations had more favorable RFS than those with KIT mutations (hazard ratio, 0.34; P = .004). Only one of the 35 GISTs with KIT exon 11 duplication mutations recurred. Patients with deletions of only one codon of KIT exon 11 had better RFS than those with another deletion type, and some KIT exon 11 substitution mutations (Trp557Arg, Val559Ala, and Leu576Pro) were also associated with favorable RFS. Patients with an identical mutation had greatly variable outcomes depending on the standard prognostic factors, notably, mitotic count. Commonly used risk stratification schemes tended to overestimate the risk for recurrence in subgroups with prognostically favorable mutations. GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11 duplication mutation or deletion of one codon have favorable RFS with surgery alone and are usually not candidates for adjuvant therapy. © 2015 by American Society of Clinical Oncology.
  • British Journal of Cancer 11/2014; 112(1):44-51. DOI:10.1038/bjc.2014.552 · 4.82 Impact Factor
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    ABSTRACT: Pregnancy, parity and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n=1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. Odds ratios were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 (4th vs. 1st quartile OR 1.60 (1.07-2.39); ptrend=0.01), and inversely associated with breast cancer diagnosed at age ≥40 (4th vs. 1st quartile OR 0.71 (0.51-1.00); ptrend=0.02). Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER) and progesterone receptor (PR) negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER+/PR+ disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER-/PR- breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor negative cancers is needed to further characterize this association.
    Cancer Research 10/2014; 74(23). DOI:10.1158/0008-5472.CAN-14-2150 · 9.28 Impact Factor
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    ABSTRACT: Objective Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Methods and Materials Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO2 laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Results Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Conclusions Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.
    International journal of radiation oncology, biology, physics 10/2014; 90(2):255–260. DOI:10.1016/j.ijrobp.2014.06.032 · 4.18 Impact Factor
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    Haematologica 10/2014; 99(10):e193-6. DOI:10.3324/haematol.2014.108258 · 5.87 Impact Factor
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    ABSTRACT: Objectives To evaluate the clinical significance of hypertension, neutropenia and thrombocytopenia as possible new biomarkers of sunitinib efficacy in non-trial metastatic renal cell carcinoma (mRCC) patients.Materials and methods181 consecutive mRCC patients were treated with sunitinib. Thirty-nine (22%) patients received sunitinib 50 mg/day 4 weeks on/ 2 weeks off, 80 patients (44%) 37.5 mg/day continuously and 62 (34%) 25 mg/day continuously as their starting dose. Treatment-induced adverse events (AE) and their impact on outcome were analysed on multiple sunitinib doses.ResultsDuring sunitinib treatment 60 patients (33%) developed ≥grade 2 hypertension, 88 (49%) ≥grade 2 neutropenia and 135 (75%) ≥grade 1 thrombocytopenia. These AEs were associated significantly with longer progression-free survival (PFS; 15.7 vs. 6.7; 14.6 vs. 6.9; 10.4 vs. 4.2 months, respectively; P <0.0001) and overall survival (OS; 37.5 vs 16.2; 33.7 vs. 13.2; 22.3 vs 13.2 months, respectively, P ≤0.008). Although only neutropenia was associated with a significantly improved PFS and OS in all sunitinib doses, a similar trend was also seen with hypertension and thrombocytopenia in all sunitinib doses. In multivariate analysis, hypertension and neutropenia were significantly associated with PFS and OS and thrombocytopenia was significantly associated with PFS. In a 12-week landmark analysis, hypertension and thrombocytopenia were significantly associated with PFS and OS. Patients who developed all three AEs (a favourable biomarker profile) had significantly better outcome than patients without these AEs (a poor biomarker profile); response rate 47% vs 4%, median PFS 27.1 vs 3.5 months and OS not reached vs 5.3 months (each P <0.0001).Conclusion Hypertension, neutropenia and thrombocytopenia were all biomarkers of sunitinib efficacy patients with mRCC. Our results may help to individualize sunitinib dosing during therapy based on these common sunitinib-related AEs.
    BJU International 09/2014; DOI:10.1111/bju.12940 · 3.13 Impact Factor
  • Heikki Joensuu
    The Lancet Oncology 08/2014; 15(10). DOI:10.1016/S1470-2045(14)70342-0 · 24.73 Impact Factor
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    ABSTRACT: BACKGROUND Little is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib.METHODS Risk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high-risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months.RESULTSFive factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence-free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5-year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P < .001 for each comparison).CONCLUSIONS The scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence. Cancer 2014 © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
    Cancer 08/2014; 120(15). DOI:10.1002/cncr.28669 · 4.90 Impact Factor
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    ABSTRACT: A number of genetic variants have been linked to increased risk of breast cancer. Little is, however, known about the prognostic significance of hereditary factors. Here, we investigated the frequency and prognostic significance of two ERBB4 promoter region variants, -782G>T (rs62626348) and -815A>T (rs62626347), in a cohort of 1010 breast cancer patients. The frequency of nine previously described somatic ERBB4 kinase domain mutations was also analyzed. Clinical material used in the study consisted of samples from the phase III, adjuvant, FinHer breast cancer trial involving 1010 women. Tumor DNA samples were genotyped for ERBB4 variants and somatic mutations using matrix-assisted laser desorption ionization/time of flight mass spectrometry. Paraffin-embedded tumor sections from all patients were immunohistochemically stained for ErbB4 expression. Association of ERBB4 genotype to distant disease-free survival (DDFS) was assessed using Kaplan-Meier and Cox regression analyses. Genotyping was successful for 91-93% of the 1010 samples. Frequencies observed for the ERBB4 variants were 2.5% and 1.3% for -782G>T and -815A>T, respectively. Variant -815A>T was significantly associated with poor survival (HR = 2.86 [95% CI 1.15-6.67], P = 0.017). In contrast, variant -782G>T was associated with well-differentiated cancer (P = 0.019). Two (0.2%) ERBB4 kinase domain mutations were found, both of which have previously been shown to be functional and promote cancer cell growth in vitro. These data present the germ-line ERBB4 variant -815A>T as a novel prognostic marker in high-risk early breast cancer and indicate the presence of rare but potentially oncogenic somatic ERBB4 mutations in breast cancer.
    PLoS ONE 07/2014; 9(7):e102388. DOI:10.1371/journal.pone.0102388 · 3.53 Impact Factor
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    ABSTRACT: Introduction In Finland, a total of 98 glioma patients, 59 with malignant glioma recurrence after surgery and 39 who had undergone surgery for newly diagnosed glioblastoma, were treated with L-BPA-F-mediated BNCT in 1999 to 2011. Normal-brain-toblood (N/B) and tumor-to-blood (T/B) 10B concentration ratios of 1 and 3.5, respectively, were assumed in dose calculations. A correlation between the calculated tumor doses and survival was not found, suggesting an incorrect estimation of the dose. In this study, the T/B and tumor-to-normal-brain (T/N) ratios are estimated using a closed 3-compartment pharmacokinetic model based on the measured blood 10B concentrations. Patients and Methods Published average rate constants obtained from 8F-BPA-PET studies, and validated for a slow intravenous L-BPA-F infusion, were applied to predict the tumor and the normal brain 10B uptake based on the 3-compartment model and the measured blood 10B levels. Altogether 22 patients with recurrent glioma, treated within a clinical trial, were evaluated using their individual measured blood 10B concentration curves. The patients received a 290 to 450 mg/kg dose of L-BPA-F administered as a 2-hour intravenous infusion. Neutron irradiation was initiated 46 to 144 minutes after the end of infusion. The 10B concentrations of peripheral venous blood samples collected at 20-minute intervals were analyzed with inductively ICP-AES. The first blood sample was taken immediately before the initiation of the L-BPA F-infusion (the baseline sample), and the last one immediately after the completion of neutron irradiation. Results and conclusions According to the 3-compartment model, the T/B ratios reached their peaks of 2.3 to 3.1 at the time of the last blood sample taken after irradiation, consequently being lower during irradiation. The model predicts differing pharmacokinetics for the brain tissue and the blood, which results in distinct T/N and T/B concentration ratio curves. The highest T/N ratio of 1.9 to 2.0 was obtained at the end of the L-BPA-F infusion, and the ratio decreased thereafter gradually to 1.5 to 1.6. Instead of examining the T/N ratio, the ratio of tumor-to-combination of 1/3 blood + 2/3 the normal brain tissue T/(1/3B+2/3N) has been proposed to be examined, as the vascular endothelium may be the main target of BNCT damage. The highest T/(1/3B+2/3N) of 1.8 to 2.0 were observed 70 to 130 minutes after end of the L-BPA F-infusions, which was the time range within which all patients received neutron irradiation. The model suggests that the treated patients received a lower tumor dose than previously predicted due to considerably lower 10B levels in the tumor. The patient doses will be re-evaluated according to the 10B levels estimated here.
    16th International Congress on Neutron Capture Therapy 2014 (http://icnct16.org/), Helsinki; 06/2014
  • Cancer Research 03/2014; 73(24 Supplement):S6-03-S6-03. DOI:10.1158/0008-5472.SABCS13-S6-03 · 9.28 Impact Factor
  • Cancer Research 03/2014; 73(24 Supplement):S1-05-S1-05. DOI:10.1158/0008-5472.SABCS13-S1-05 · 9.28 Impact Factor
  • Cancer Research 03/2014; 73(24 Supplement):P1-08-06-P1-08-06. DOI:10.1158/0008-5472.SABCS13-P1-08-06 · 9.28 Impact Factor
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    ABSTRACT: We have previously shown the prognostic importance of tumor infiltrating lymphocytes (TILs) in newly-diagnosed triple-negative breast cancer (TNBC) using tumor samples from a large clinical trial cohort. In this study, we aimed to validate these findings and also investigate associations with trastuzumab benefit in HER2-overexpressing disease (HER2+). A prospective-retrospective study was conducted using samples from the FinHER adjuvant, phase III trial that enrolled 1010 early-stage BC patients, 778 of whom were HER2-non-amplified. Those with HER2+ disease (n=232) were randomized to 9 weeks of trastuzumab or no trastuzumab in addition to chemotherapy. Two pathologists independently quantified stromal TILs in 935 (92·6%) available slides. The primary endpoint of distant disease-free survival (DDFS) and interactions with trastuzumab were studied in Cox regression models. Confirming our previous findings in TNBC (n=134), each 10% increase in TILs located in the stroma was significantly associated with decreased distant recurrence in TNBC; for DDFS hazard-ratio adjusted for clinic-pathological factors: 0·77; 95%CI 0·61-0·98,P=0·02. In HER2+ BC (n=209), each 10% increase in lymphocytic infiltration was significantly associated with decreased distant recurrence in patients randomized to the trastuzumab arm (DDFS Pinteraction=0·025). Higher levels of TILs present at diagnosis were significantly associated with decreased distant recurrence rates in primary TNBC. This data confirms our previous data and further support that TILs should be considered a robust prognostic factor in this BC subtype. We also report for the first time an association between higher levels of TILs and increased trastuzumab benefit in HER2+ disease. Further research into why some TN and HER2+ BCs can or cannot generate a host anti-tumor immune response and how trastuzumab can favorably alter the immune microenvironment is warranted.
    Annals of Oncology 03/2014; 25(8). DOI:10.1093/annonc/mdu112 · 6.58 Impact Factor
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    Mark Barok, Heikki Joensuu, Jorma Isola
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    ABSTRACT: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and generally well tolerated when administered as a single agent to treat advanced breast cancer. Efficacy has now been demonstrated in randomized trials as first line, second line, and later than the second line treatment of advanced breast cancer. T-DM1 is currently being evaluated as adjuvant treatment for early breast cancer. It has several mechanisms of action consisting of the anti-tumor effects of trastuzumab and those of DM1, a cytotoxic anti-microtubule agent released within the target cells upon degradation of the human epidermal growth factor receptor-2 (HER2)-T-DM1 complex in lysosomes. The cytotoxic effect of T-DM1 likely varies depending on the intracellular concentration of DM1 accumulated in cancer cells, high intracellular levels resulting in rapid apoptosis, somewhat lower levels in impaired cellular trafficking and mitotic catastrophe, while the lowest levels lead to poor response to T-DM1. Primary resistance of HER2-positive metastatic breast cancer to T-DM1 appears to be relatively infrequent, but most patients treated with T-DM1 develop acquired drug resistance. The mechanisms of resistance are incompletely understood, but mechanisms limiting the binding of trastuzumab to cancer cells may be involved. The cytotoxic effect of T-DM1 may be impaired by inefficient internalization or enhanced recycling of the HER2-T-DM1 complex in cancer cells, or impaired lysosomal degradation of trastuzumab or intracellular trafficking of HER2. The effect of T-DM1 may also be compromised by multidrug resistance proteins that pump DM1 out of cancer cells. In this review we discuss the mechanism of action of T-DM1 and the key clinical results obtained with it, the combinations of T-DM1 with other cytotoxic agents and anti-HER drugs, and the potential resistance mechanisms and the strategies to overcome resistance to T-DM1.
    Breast cancer research: BCR 03/2014; 16(2):R22. DOI:10.1186/bcr3621 · 5.88 Impact Factor
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    ABSTRACT: Background: Prokineticin-1 (PROK1) and prokineticin-2 (PROK2) are chemokine-like proteins that may influence cancer growth by regulating host defence and angiogenesis. Their significance in viral infection-associated cancer is incompletely understood. We studied prokineticins in Merkel cell carcinoma (MCC), a skin cancer linked with Merkel cell polyomavirus (MCPyV) infection. Methods: Carcinoma cell expression of PROK1 and PROK2 and their receptors (PROKR1 and PROKR2) was investigated with immunohistochemistry, and tumour PROK1 and PROK2 mRNA content with quantitative PCR from 98 MCCs. Subsets of tumour infiltrating leukocytes were identified using immunohistochemistry. Results: Merkel cell polyomavirus-positive MCCs had higher than the median PROK2 mRNA content, whereas MCPyV-negative MCCs contained frequently PROK1 mRNA. Cancers with high tumour PROK2 mRNA content had high counts of tumour infiltrating macrophages (CD68+ and CD163+ cells). Patients with higher than the median PROK2 mRNA content had 44.9% 5-year survival compared with 23.5% among those with a smaller content (hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.34–0.84; P=0.005), whereas the presence of PROK1 mRNA in tumour was associated with unfavourable survival (P=0.052). Conclusions: The results suggest that prokineticins are associated with MCPyV infection and participate in regulation of the immune response in MCC, and may influence outcome of MCC patients.
    British Journal of Cancer 02/2014; 110(6). DOI:10.1038/bjc.2014.20 · 4.82 Impact Factor
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    ABSTRACT: Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade IV) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT-imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared to the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3), as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histological grade of the tumor suggesting MDGI as a novel marker for malignant gliomas.
    Molecular Cancer Therapeutics 02/2014; 13(4). DOI:10.1158/1535-7163.MCT-13-0684 · 6.11 Impact Factor
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    ABSTRACT: Mutations of the tumor suppressor TP53 are present in many forms of human cancer and are associated with increased tumor cell invasion and metastasis. Several mechanisms have been identified for promoting dissemination of cancer cells with TP53 mutations, including increased targeting of integrins to the plasma membrane. Here, we demonstrate a role for the filopodia-inducing motor protein Myosin-X (Myo10) in mutant p53-driven cancer invasion. Analysis of gene expression profiles from 2 breast cancer data sets revealed that MYO10 was highly expressed in aggressive cancer subtypes. Myo10 was required for breast cancer cell invasion and dissemination in multiple cancer cell lines and murine models of cancer metastasis. Evaluation of a Myo10 mutant without the integrin-binding domain revealed that the ability of Myo10 to transport β1 integrins to the filopodia tip is required for invasion. Introduction of mutant p53 promoted Myo10 expression in cancer cells and pancreatic ductal adenocarcinoma in mice, whereas suppression of endogenous mutant p53 attenuated Myo10 levels and cell invasion. In clinical breast carcinomas, Myo10 was predominantly expressed at the invasive edges and correlated with the presence of TP53 mutations and poor prognosis. These data indicate that Myo10 upregulation in mutant p53-driven cancers is necessary for invasion and that plasma-membrane protrusions, such as filopodia, may serve as specialized metastatic engines.
    The Journal of clinical investigation 02/2014; 124(3). DOI:10.1172/JCI67280 · 13.77 Impact Factor

Publication Stats

23k Citations
3,482.36 Total Impact Points

Institutions

  • 1996–2015
    • Helsinki University Central Hospital
      • Department of Oncology
      Helsinki, Uusimaa, Finland
  • 1996–2014
    • University of Helsinki
      • • Department of Oncology
      • • Molecular/Cancer Biology Laboratory
      • • Department of Medical Genetics
      Helsinki, Uusimaa, Finland
  • 2006–2008
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
    • The Ohio State University
      • Pathology
      Columbus, OH, United States
  • 2007
    • University of Toronto
      Toronto, Ontario, Canada
  • 1995–2003
    • Uppsala University
      Uppsala, Uppsala, Sweden
  • 2000
    • Tampere University Hospital (TAUH)
      Tammerfors, Province of Western Finland, Finland
    • New York University
      • Department of Cell Biology
      New York City, NY, United States
  • 1999
    • University of Oulu
      Uleoborg, Oulu, Finland
  • 1988–1998
    • University of Turku
      • • Department of Oncology and Radiotherapy
      • • Department of Surgery
      • • Department of Pathology
      Turku, Province of Western Finland, Finland
  • 1986–1997
    • Turku University Hospital
      • Department of Obstetrics and Gynecology
      Turku, Western Finland, Finland
  • 1994
    • Turku PET Centre
      Turku, Province of Western Finland, Finland
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 1992–1994
    • Kuopio University Hospital
      • Radiotherapy Unit
      Kuopio, Northern Savo, Finland
  • 1993
    • Finnish Cancer Registry, Helsinki
      Helsinki, Southern Finland Province, Finland