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Henriksson, Roger
Publications (10 of 190) Show all publications
Bartek, J. J., Förander, P., Thurin, E., Wangerid, T., Henriksson, R., Hesselager, G. & Jakola, A. S. (2019). Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study. Frontiers in Neurology, 10, Article ID 43.
Open this publication in new window or tab >>Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study
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2019 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 43Article in journal (Refereed) Published
Abstract [en]

Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009–2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 ± 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (< 4 vs. ≥4 cm), those with ≥4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (< 65 years) vs. elderly (≥65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
vestibular schwannoma, neurosurgery, outcome, complications, stereotactic radiosurgery, hematoma, infection, neurological deficit
National Category
Neurology Surgery
Identifiers
urn:nbn:se:umu:diva-156596 (URN)10.3389/fneur.2019.00043 (DOI)000457162000001 ()
Funder
Swedish Research Council, 2017-00944
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
Faraz, M., Herdenberg, C., Holmlund, C., Henriksson, R. & Hedman, H. (2018). A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors. Journal of Biological Chemistry, 293(9), 3421-3435
Open this publication in new window or tab >>A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors
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2018 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 9, p. 3421-3435Article in journal (Refereed) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors. The effects of the shRNAs on the ability of LRIG1 to down-regulate platelet-derived growth factor receptor α expression were evaluated. On the basis of these results, we present an LRIG1 protein interaction network with many newly identified components. The network contains the apparently functionally important LRIG1-interacting proteins RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, and LRIG3, together with GLRX3, PTPRK, and other proteins. In silico analyses of The Cancer Genome Atlas data sets revealed consistent correlations between the expression of the transcripts encoding LRIG1 and its interactors ZBTB16 and PTPRK and inverse correlations between the transcripts encoding LRIG1 and GLRX3. We further studied the LRIG1 function–promoting paraoxonase PON2 and found that it co-localized with LRIG1 in LRIG1-transfected cells. The proposed LRIG1 protein interaction network will provide leads for future studies aiming to understand the molecular functions of LRIG1 and the regulation of growth factor signaling.

Place, publisher, year, edition, pages
The American Society for Biochemistry and Molecular Biology, 2018
Keywords
LRIG1, PDGFRA, PON2, PTPRK, ZBTB16, platelet-derived growth factor-C (PDGF-C), protein expression, protein-protein interaction, receptor tyrosine kinase, yeast two-hybrid
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-147386 (URN)10.1074/jbc.M117.807487 (DOI)000426562800032 ()29317492 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-06-09Bibliographically approved
Sharp, L., Westman, B., Olofsson, A., Leppänen, A. & Henriksson, R. (2018). Access to supportive care during and after cancer treatment and the impact of socioeconomic factors. Acta Oncologica, 57(10), 1303-1310
Open this publication in new window or tab >>Access to supportive care during and after cancer treatment and the impact of socioeconomic factors
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 10, p. 1303-1310Article in journal (Refereed) Published
Abstract [en]

Background: Sweden's national cancer strategy points out several areas of cancer care that need improvements. Among them the need for supportive care resources to be accessible through the entire cancer trajectory and the reduction of socioeconomic inequalities. The aim of this study was to compare the patient-reported access to supportive care in the Stockholm-Gotland region between patients diagnosed in 2014 and 2016. The aim was also to describe how socioeconomic and other demographic factors impact access to supportive care.

Material and methods: All patients with gynaecological, head and neck, haematological and upper gastrointestinal cancers diagnosed in the Stockholm-Gotland regions were identified through the Swedish Cancer Registries. Data were collected via a questionnaire on demographic, socioeconomic factors and patients' perception (n=1872) of access to supportive care. Data were summarized using descriptive statistics and logistic regression was used for relevant variables.

Results: Access to some supportive care resources, such as contact nurses (CNs) and individual written care plans (IWCPs) had significantly improved from 2014 to 2016. The proportion of patients that had received information about patient advocacy groups (PAGs) had also improved but remained on a relatively low level (29 and 35%, respectively). The proportion of patients being refereed to palliative care (PC) did not change between 2014 and 2016. In total, 10% of the patients reported to having received information on second medical opinion (SMO). Patients that had undergone multimodality cancer treatment were more likely to report access to supportive care, and those with lower education levels were more likely to have access to CNs and IWCPs.

Conclusion: Access to some of the supportive care resources have shown improvements in the Stockholm-Gotland region but further efforts are required, especially regarding access to PC, information about PAGs and SMOs.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-153840 (URN)10.1080/0284186X.2018.1484157 (DOI)000448595500004 ()29947281 (PubMedID)
Available from: 2018-12-11 Created: 2018-12-11 Last updated: 2018-12-11Bibliographically approved
Sjöström, O., Silander, G., Syk, I., Henriksson, R., Melin, B. S. & Hellquist, B. N. (2018). Disparities in colorectal cancer between Northern and Southern Sweden – a report from the new RISK North database. Acta Oncologica, 57(12), 1622-1630
Open this publication in new window or tab >>Disparities in colorectal cancer between Northern and Southern Sweden – a report from the new RISK North database
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 12, p. 1622-1630Article in journal (Refereed) Published
Abstract [en]

Background: Geographic cancer health disparities have been reported in Sweden. The disparities are not fully understood, but may be attributed to differences in exposure to risk factors as well as differences in health care, socioeconomics and demography. The aim of this study was to describe the new nationwide population based RISK North database and its potential by analysing health disparities in colorectal cancer between Northern and Southern Sweden.

Methods: Cancer-specific data from the National Cancer Quality Registers for colorectal, gastric and oesophageal cancer and brain tumours were linked to several nationwide registers hereby creating a new database – RISK North. To exemplify the potential of RISK North, we analyzed differences in colorectal cancer incidence, mortality and survival in relation to gender, age, cohabitation and education between Northern and Southern Sweden 2007–2013.

Results: In colon cancer, the age-adjusted incidence per 100.000 was lower in Northern than Southern Sweden, 35.9 in the North vs. 41.1 in the South (p < .01); mortality rates were 11.0 vs. 12.2 (p < .01). For rectal cancer, incidence rates were 17.6 vs. 19.7 (p < .01) and mortality rates 5.33 vs. 5.89 (p = .07), respectively. The largest difference in incidence was demonstrated for colon cancer among individuals >79 years old (190. vs. 237, i.e., ∼20%). Survival in colon cancer was higher in Southern Sweden, HR 0.92 (0.87–0.98) adjusted for age, gender, co-habiting, education and m-stage at diagnosis. No difference in survival was seen for rectal cancer.

Conclusions: The new RISK North database enabled analysis of cancer disparities between Northern and Southern Sweden. The incidence of colorectal cancer were lower in the North of Sweden whereas colon cancer survival was higher in the South. These differences can be further analysed utilising the RISK North database.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-155108 (URN)10.1080/0284186X.2018.1497300 (DOI)000453867800005 ()30280619 (PubMedID)
Funder
Swedish Research CouncilVästerbotten County Council
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-01-14Bibliographically approved
Karlsson, T., Kvarnbrink, S., Holmlund, C., Botling, J., Micke, P., Henriksson, R., . . . Hedman, H. (2018). LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease. Lung Cancer, 125, 174-184
Open this publication in new window or tab >>LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease
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2018 (English)In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 125, p. 174-184Article in journal (Refereed) Published
Abstract [en]

Objectives: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises the integral membrane proteins LRIG1, LRIG2 and LRIG3. LRIG1 is frequently down-regulated in human cancer, and high levels of LRIG1 in tumor tissue are associated with favorable clinical outcomes in several tumor types including non-small cell lung cancer (NSCLC). Mechanistically, LRIG1 negatively regulates receptor tyrosine kinases and functions as a tumor suppressor. However, the details of the molecular mechanisms involved are poorly understood, and even less is known about the functions of LRIG2 and LRIG3. The aim of this study was to further elucidate the functions and molecular interactions of the LRIG proteins.

Materials and methods: A yeast two-hybrid screen was performed using a cytosolic LRIG3 peptide as bait. In transfected human cells, co-immunoprecipitation and co-localization experiments were performed. Proximity ligation assay was performed to investigate interactions between endogenously expressed proteins. Expression levels of LMO7 and LIMCH1 in normal and malignant lung tissue were investigated using qRT-PCR and through in silico analyses of public data sets. Finally, a clinical cohort comprising 355 surgically treated NSCLC cases was immunostained for LMO7.

Results: In the yeast two-hybrid screen, the two paralogous proteins LMO7 and LIMCH1 were identified as interaction partners to LRIG3. LMO7 and LIMCH1 co-localized and co-immunoprecipitated with both LRIG1 and LRIG3. Endogenously expressed LMO7 was in close proximity of both LRIG1 and LRIG3. LMO7 and LIMCH1 were highly expressed in normal lung tissue and down-regulated in malignant lung tissue. LMO7 immunoreactivity was shown to be a negative prognostic factor in LRIG1 positive tumors, predicting poor patient survival.

Conclusion: These findings suggest that LMO7 and LIMCH1 physically interact with LRIG proteins and that expression of LMO7 is of clinical importance in NSCLC.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Non-small cell lung cancer, Lung cancer, Prognosis, LRIG1, LRIG3, LMO7, LIMCH1
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-154070 (URN)10.1016/j.lungcan.2018.09.017 (DOI)000450378500025 ()30429017 (PubMedID)
Funder
Swedish Cancer SocietyThe Kempe FoundationsVästerbotten County Council
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12Bibliographically approved
Mao, F., Holmlund, C., Faraz, M., Wang, W., Bergenheim, T., Kvarnbrink, S., . . . Hedman, H. (2018). Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma. Oncogenesis, 7, Article ID 13.
Open this publication in new window or tab >>Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma
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2018 (English)In: Oncogenesis, E-ISSN 2157-9024, Vol. 7, article id 13Article in journal (Refereed) Published
Abstract [en]

Recently, a genome-wide association study showed that a single nucleotide polymorphism (SNP) —rs11706832—in intron 2 of the human LRIG1 (Leucine-rich repeats and immunoglobulin-like domains 1) gene is associated with susceptibility to glioma. However, the mechanism by which rs11706832 affects glioma risk remains unknown; additionally, it is unknown whether the expression levels of LRIG1 are a relevant determinant of gliomagenesis. Here, we investigated the role of Lrig1 in platelet-derived growth factor (PDGF)-induced experimental glioma in mice by introducing mono-allelic and bi-allelic deletions of Lrig1 followed by inducing gliomagenesis via intracranial retroviral transduction of PDGFB in neural progenitor cells. Lrig1 was expressed in PDGFB-induced gliomas in wild-type mice as assessed using in situ hybridization. Intriguingly, Lrig1-heterozygous mice developed higher grade gliomas than did wild-type mice (grade IV vs. grade II/III, p = 0.002). Reciprocally, the ectopic expression of LRIG1 in the TB107 high-grade human glioma (glioblastoma, grade IV) cell line decreased the invasion of orthotopic tumors in immunocompromised mice in vivo and reduced cell migration in vitro. Concomitantly, the activity of the receptor tyrosine kinase MET was downregulated, which partially explained the reduction in cell migration. In summary, Lrig1 is a haploinsufficient suppressor of PDGFB-driven glioma, possibly in part via negative regulation of MET-driven cell migration and invasion. Thus, for the first time, changes in physiological Lrig1 expression have been linked to gliomagenesis, whereby the SNP rs11706832 may affect glioma risk by regulating LRIG1 expression.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147385 (URN)10.1038/s41389-017-0012-8 (DOI)000429469500001 ()29391393 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-06-09Bibliographically approved
Lindquist, D., Alsina, F. C., Herdenberg, C., Larsson, C., Höppener, J., Wang, N., . . . Hedman, H. (2018). LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer. International journal of oncology, 52(4), 1189-1197
Open this publication in new window or tab >>LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
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2018 (English)In: International journal of oncology, ISSN 1791-2423, Vol. 52, no 4, p. 1189-1197Article in journal (Refereed) Published
Abstract [en]

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.

Keywords
thyroid cancer, LRIG1, RET, C634R, M918T, MEN2A, MEN2B
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-145641 (URN)10.3892/ijo.2018.4273 (DOI)000427164400013 ()29436694 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-06-09Bibliographically approved
Westman, B., Kirkpatrick, L., Ebrahim, F., Henriksson, R. & Sharp, L. (2018). Patient-reported experiences on supportive care strategies following the introduction of the first Swedish national cancer strategy and in accordance with the new patient act. Acta Oncologica, 57(3), 382-392
Open this publication in new window or tab >>Patient-reported experiences on supportive care strategies following the introduction of the first Swedish national cancer strategy and in accordance with the new patient act
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 382-392Article in journal (Refereed) Published
Abstract [en]

Introduction: Several supportive care strategies are described in Swedish legislation and policy documents, such as the National Cancer Strategy and the Patient act. No previous systematic evaluation from a patient perspective has been performed. The aim of this study was to evaluate how these supportive care strategies are experienced by patients treated for cancer in the Stockholm-Gotland region.

Material and methods: In this cross-sectional study, we identified patients (diagnosed with gynaecological, haematological, upper gastrointestinal and head and neck cancer during 2014) from the Swedish Cancer Register. The European Organization of Research and Treatment of Cancer, EORTC, Quality of Life Questionnaires, QLQ-C30, Information QLQ-INFO25 and a study-specific questionnaire was used to collect data during follow-up after cancer treatment. We collected data on 869 cancer patients' perception of availability and access to supportive care strategies and how they were experienced.

Results: Among the supportive care strategies suggested in the legislation and policy documents, just over half of the patients (n=393, 53%) reported that they had access to a contact nurse, while 43% (n=312) had received an individual written care plan and 16% (n=137) had been referred to palliative care. Only 29% (n=218) of the patients reported that they had received information about patient advocacy groups and 8% (n=62) on medical second opinions from their cancer care team.

Discussion: The supportive care strategies suggested in Swedish legislation and policy documents may be useful but are only available for some patients. The implementation goals for the National Cancer Strategy and the Swedish Patient act have not been reached.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-144966 (URN)10.1080/0284186X.2017.1418089 (DOI)000423754200012 ()29276836 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-06-09Bibliographically approved
Ellingson, B. M., Abrey, L. E., Garcia, J., Chinot, O., Wick, W., Saran, F., . . . Cloughesy, T. F. (2018). Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide, and bevacizumab or placebo. Neuro-Oncology, 20(11), 1525-1535
Open this publication in new window or tab >>Post-chemoradiation volumetric response predicts survival in newly diagnosed glioblastoma treated with radiation, temozolomide, and bevacizumab or placebo
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2018 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, no 11, p. 1525-1535Article in journal (Refereed) Published
Abstract [en]

Background. In the current study we used contrast-enhanced T1 subtraction maps to test whether early changes in enhancing tumor volume are prognostic for overall survival (OS) in newly diagnosed glioblastoma (GBM) patients treated with chemoradiation with or without bevacizumab (BV). Methods. Seven hundred ninety-eight patients (404 BV and 394 placebo) with newly diagnosed GBM in the AVAglio trial (NCT00943826) had baseline MRI scans available, while 337 BV-treated and 269 placebo-treated patients had > 4 MRI scans for response evaluation. The volume of contrast-enhancing tumor was quantified and used for subsequent analyses. Results. A decrease in tumor volume during chemoradiation was associated with a longer OS in the placebo group (hazard ratio [HR] = 1.578, P < 0.0001) but not BV-treated group (HR = 1.135, P = 0.4889). Results showed a higher OS in patients on the placebo arm with a sustained decrease in tumor volume using a post-chemoradiation baseline (HR = 1.692, P = 0.0005), and a trend toward longer OS was seen in BV-treated patients (HR = 1.264, P = 0.0724). Multivariable Cox regression confirmed that sustained response or stable disease was prognostic for OS (HR = 0.7509, P = 0.0127) when accounting for age (P = 0.0002), KPS (P = 0.1516), postsurgical tumor volume (P < 0.0001), O6-methylguanine-DNA methyltransferase status (P < 0.0001), and treatment type (P = 0.7637) using the post-chemoradiation baseline. Conclusions. The post-chemoradiation timepoint is a better baseline for evaluating efficacy in newly diagnosed GBM. Early progression during the maintenance phase is consequential in predicting OS, supporting the use of progression-free survival rates as a meaningful surrogate for GBM.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
bevacizumab, clinical trials, GBM, glioblastoma, MRI, response assessment, T1 subtraction
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-153549 (URN)10.1093/neuonc/noy064 (DOI)000448665500012 ()29897562 (PubMedID)
Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2018-11-22Bibliographically approved
Dahlrot, R. H., Dowsett, J., Fosmark, S., Malmstrom, A., Henriksson, R., Boldt, H., . . . Kristensen, B. W. (2018). Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis. Neuropathology and Applied Neurobiology, 44(2), 172-184
Open this publication in new window or tab >>Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis
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2018 (English)In: Neuropathology and Applied Neurobiology, ISSN 0305-1846, E-ISSN 1365-2990, Vol. 44, no 2, p. 172-184Article in journal (Refereed) Published
Abstract [en]

Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status.

Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population‐based Region of Southern Denmark (RSD)‐cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM‐patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules.

Results: When divided at the median, patients with low expression of MGMT protein (AF‐low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS‐cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF‐low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF‐low had the best outcome; median OS 23.1 and 20.0 months, respectively.

Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour‐specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

Keywords
glioblastoma multiforme, glioma, image analysis, MGMT, O-6-methylguanine-DNA methyltransferase, ognosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-145602 (URN)10.1111/nan.12415 (DOI)000425641000006 ()28574607 (PubMedID)
Available from: 2018-04-17 Created: 2018-04-17 Last updated: 2018-06-09Bibliographically approved
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