Anders Berglund

CUNY Graduate Center, New York City, New York, United States

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Publications (48)215.05 Total impact

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    ABSTRACT: Patient safety is of the utmost importance in health care. The patient safety culture in an institution has great impact on patient safety. To enhance patient safety and to design strategies to reduce medical injuries, there is a current focus on measuring the patient safety culture. The aim of the present study was to describe the patient safety culture in an ED at two different hospitals before and after a Quality improvement (QI) project that was aimed to enhance patient safety.
    BMC Health Services Research 07/2014; 14(1):296. · 1.77 Impact Factor
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    ABSTRACT: Abstract Background. Commonly used inhalational hypnotics, such as sevoflurane, are pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and anti-oxidative. A few clinical studies have indicated similar effects in patients. We examined the possible association between patient survival after radical cancer surgery and the use of sevoflurane or propofol anaesthesia. Patients and methods. Demographic, anaesthetic, and surgical data from 2,838 patients registered for surgery for breast, colon, or rectal cancers were included in a database. This was record-linked to regional clinical quality registers. Cumulative 1- and 5-year overall survival rates were assessed using the Kaplan-Meier method, and estimates were compared between patients given propofol (n = 903) or sevoflurane (n = 1,935). In a second step, Cox proportional hazard models were calculated to assess the risk of death adjusted for potential effect modifiers and confounders. Results. Differences in overall 1- and 5-year survival rates for all three sites combined were 4.7% (p = 0.004) and 5.6% (p < 0.001), respectively, in favour of propofol. The 1-year survival for patients operated for colon cancer was almost 10% higher after propofol anaesthesia. However, after adjustment for several confounders, the observed differences were not statistically significant. Conclusion. Propofol anaesthesia might be better in surgery for some cancer types, but the retrospective design of this study, with uneven distributions of several confounders, distorted the picture. These uncertainties emphasize the need for a randomized controlled trial.
    Upsala journal of medical sciences. 05/2014;
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    ABSTRACT: Abstract Objective. In countries with widespread prostate cancer screening there has been strong stage migration, but little is known about changes within clinical risk categories. Such data are important for the proper interpretation of studies that recruited cases in an earlier era. The purpose of this study was to examine stage migration between and within clinical risk categories. Material and methods. Using the population-based National Prostate Cancer Register (NPCR) of Sweden, changes in the distribution of prostate-specific antigen (PSA), Gleason score, tumor stage and volume overall between and within clinical risk categories were examined in 120 228 prostate cancer cases diagnosed from 1998 to 2011. Results. Between 1998 and 2011, there was a two-fold increase in the proportion of low-risk prostate cancer (stage T1/T2, Gleason score 2-6 and PSA <10 ng/ml), from 14% to 28%, and more than a two-fold decrease in the proportion of metastatic disease, from 25% to 11%. The proportion of men in the low-risk category with T1c tumors increased two-fold, from 36% to 71%, and PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%. The proportion of men with less than 25% of cores involved with cancer increased from 41% to 52% between 2003-2006 and 2007-2011. Conclusions. Low-risk cases today have substantially lower tumor volume and PSA levels than low-risk cases diagnosed in 1998, indicating that outcomes in studies that recruited cases in previous decades represent worst case scenarios.
    Scandinavian journal of urology. 03/2014;
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    ABSTRACT: Claudins (CLDNs) are central components of tight junctions that regulate epithelial-cell barrier function and polarity. Altered CLDN expression patterns have been demonstrated in numerous cancer types and lineage-specific CLDNs have been proposed as therapy targets. The objective of this study was to assess which fraction of patients with non-small-cell-lung cancer (NSCLC) express CLDN6 and CLDN18 isoform 2 (CLDN18.2). Protein expression of CLDN6 and CLDN18.2 was examined by immunohistochemistry on a tissue microarray (n = 355) and transcript levels were supportively determined based on gene expression microarray data from fresh-frozen NSCLC tissues (n = 196). Both were analyzed with regard to frequency, distribution, and association with clinical parameters. Immunohistochemical analysis of tissue sections revealed distinct membranous positivity of CLDN6 (6.5%) and CLDN18.2 (3.7%) proteins in virtually non-overlapping subgroups of adenocarcinomas and large-cell carcinomas. Pneumocytes and bronchial epithelial cells were consistently negative. Corresponding to the protein expression, in subsets of non-squamous lung carcinoma high mRNA levels of CLDN6 (7-16%) and total CLDN18 (5-12%) were observed. Protein expression correlated well with total mRNA expression of the corresponding gene (rho = 0.4-0.8).CLDN18.2 positive tumors were enriched among slowly proliferating, thyroid transcription factor 1 (TTF-1)-negative adenocarcinomas, suggesting that isoform-specific CLDN expression may delineate a specific subtype. Noteworthy, high CLDN6 protein expression was associated with worse prognosis in lung adenocarcinoma in the univariate (HR: 1.8; p = 0.03) and multivariate COX regression model (HR: 1.9; p = 0.02). These findings encourage further clinical exploration of targeting ectopically activated CLDN expression as a valuable treatment concept in NSCLC. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 03/2014; · 6.20 Impact Factor
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    ABSTRACT: Background. Few studies to date have described the clinical features of malignant melanoma in young adulthood. Also, little is known about patterns of care in young patients. We examined and compared clinical characteristics, management and survival between young adult (15-39 years) and older adult melanoma patients in Central Sweden. Material and methods. Patients diagnosed with invasive malignant melanoma between 1997 and 2011 were identified in the Regional Quality Register of Cutaneous Malignant Melanoma in Central Sweden, a population-based register covering a source population of about two million. Data on clinical characteristics, management and survival were retrieved and compared according to age at diagnosis. Results. Of 5915 patients included in the study, 584 (9.9%) were between 15 and 39 years of age at diagnosis. Compared with older patients, young adult patients were more likely to be female, with higher proportions of thin, non-ulcerated melanomas, superficial spreading melanoma and melanomas located on the lower extremity. Young adults had shorter waiting times for surgical procedures and a higher proportion received surgical treatment according to guidelines. Overall, young patients had better relative survival than older patients. Age-related survival differences varied by stage of disease at diagnosis, and were most prominent in stage II disease. Conclusion. The observed differences in clinical characteristics, management and survival between young adult and older melanoma patients call for an improved understanding of not only disease etiology but also factors driving management decisions. A better understanding of these differences may help improve care and prognosis for melanoma patients of all ages.
    Acta oncologica (Stockholm, Sweden) 12/2013; · 2.27 Impact Factor
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    ABSTRACT: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC). Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect. Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms. The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting. NCT00598156.
    Annals of Oncology 06/2013; · 7.38 Impact Factor
  • Stacy Loeb, Anders Berglund, Pär Stattin
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    ABSTRACT: PURPOSE: Prior studies have reported underutilization of deferred treatment (i.e. active surveillance or watchful waiting) for low-risk prostate cancer in the United States. Our objective was to examine contemporary trends in active surveillance and watchful waiting in the nationwide Swedish prostate cancer registry. We also examined factors associated with selection of deferred management, which might provide insight into the rational diffusion of this important management strategy. MATERIALS AND METHODS: We identified 57,713 men with very low-risk (T1c, Gleason ≤6, PSA <10 ng/ml, PSA density <0.20 ng/ml/cc, ≤2 positive biopsy cores or <25% of cores positive), low-risk (T1-T2, Gleason ≤6, and PSA <10), and intermediate-risk prostate cancer (T1-T2, Gleason 7 and/or PSA 10-20) in the Prostate Cancer database Sweden (PCBaSe) from 1998-2011. Subclassification of very low-risk disease, and active surveillance versus watchful waiting was possible beginning in 2007. We examined primary treatment selection by risk group, and used logistic regression to evaluate factors associated with deferred treatment. RESULTS: Overall, 13,272 (46%) men with low-risk and 8,695 (30%) with intermediate-risk prostate cancer chose deferred treatment. Since 2007, 59%, 41%, and 16% of very low, low and intermediate-risk prostate cancer chose active surveillance. Age was by far the strongest determinant of deferred treatment. Education, marital status and comorbidity were significantly but weakly associated with deferring treatment. CONCLUSIONS: Deferred treatment for low and intermediate-risk prostate cancer was frequently utilized in Sweden. Dissociating diagnosis from treatment in men with a low risk of progression can decrease the rate of overtreatment.
    The Journal of urology 05/2013; · 4.02 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate whether longitudinal changes in health-related quality of life (HRQoL) among breast cancer patients vary by prediagnosis occupational status or postdiagnosis changes in working time. METHODS: We identified 1573 patients in the Breast Cancer Quality Register of Central Sweden and asked them to participate in a longitudinal questionnaire study. A total of n = 841 women completed three questionnaires within a mean time of 4, 16, and 38 months postdiagnosis. Generalized estimating equation models were used to examine changes in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the Breast Cancer-Specific Quality of Life Questionnaire subscales stratified by prediagnosis occupational status and postdiagnosis changes in working time. RESULTS: Over time, the proportion of employed women reporting good functioning increased more, and the proportion reporting a high level of symptoms decreased more compared with women on sick leave/disability pension and retirement pensioners (p < 0.001). The latter two also showed a worsening in several subscales (p < 0.05). Among employed women, more consistent improvements in role and social functioning were observed among those with an increase/no change in working time than among those who had decreased it or stopped working (p < 0.05). A decrease in the proportion reporting pain was observed among women with an increase/no change in working time compared with women with decreased working time, among whom the proportion reporting pain increased (p = 0.008). CONCLUSIONS: Being employed prediagnosis and resuming work to the same extent as prior to the breast cancer diagnosis are associated with consistent improvements in HRQoL. These results highlight the importance of interventions to improve HRQoL and policies to support return to work following diagnosis. Copyright © 2013 John Wiley & Sons, Ltd.
    Psycho-Oncology 04/2013; · 3.51 Impact Factor
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    ABSTRACT: A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma-infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.
    Cancer Letters 01/2013; · 4.26 Impact Factor
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    ABSTRACT: A prognostic impact of immunoglobulin kappa C (IGKC) expression has been described in cancer. We analysed the influence of B-cell and plasma cell markers, as well as IGKC expression, in non-small lung cancer (NSCLC) using immunohistochemistry on a tissue microarray. IGKC protein expression was independently associated with longer survival, with particular impact in the adenocarcinoma subgroup. Moreover, a correlation was seen with CD138+ cells, but not with CD20. CD138 expression revealed a comparable association with survival. In conclusion, IGKC expression in stroma-infiltrating plasma cells is a prognostic marker in NSCLC, supporting emerging treatment concepts that exploit the humoral immune response.
    Cancer letters 01/2013; · 4.86 Impact Factor
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    ABSTRACT: Background: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multi-gene signatures in clinical practice is unclear and the biological importance of individual genes is difficult to assess as the published signatures virtually do not overlap Methods: Here we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data was used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level p<0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n=860). RESULTS: The meta-analysis revealed 14 genes that were significantly associated with survival (p<0.001) with a false discovery rate <1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from two independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup. CONCLUSIONS: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics.
    Clinical Cancer Research 10/2012; · 7.84 Impact Factor
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    ABSTRACT: To investigate associations between comorbidity burden, management, and mortality in women with breast cancer. A total of 42,646 women diagnosed with breast cancer between 1992 and 2008 were identified in two Clinical Quality Registers in Central Sweden. Breast cancer-specific, conditional breast cancer, competing-cause and all-cause mortality were estimated in relation to comorbidity burden assessed by the Charlson comorbidity index. All analyses were stratified by stage at diagnosis using competing risk analyses, and all-cause mortality was estimated as a function of follow-up time. Following adjustment for age and calendar period, breast conserving surgery was significantly less likely to be offered to women with severe comorbidity (OR 0.63; 95 % CI 0.58-0.69). Similarly, the proportion treated with radiotherapy, tamoxifen, or chemotherapy was lower in women with severe compared to those with no comorbidity. In women with early stage disease, breast cancer-specific mortality was higher among patients with severe comorbidity (sHR 1.47; 95 % CI 1.11-1.94). In all stages of breast cancer, conditional breast cancer and competing-cause mortality were elevated in women with severe comorbidity. For all stages, the relative risk of all-cause mortality between women with severe versus no comorbidity varied by time since diagnosis, and was most pronounced at early follow-up. Comorbidity affects treatment decisions and mortality. In women with early stage breast cancer, severe comorbidity was associated not only with conditional breast cancer, competing-cause and all-cause mortality, but also breast cancer-specific mortality. The observed differences in breast cancer-specific mortality may be due to less extensive treatment, impaired tumor defense and differences in general health status and lifestyle factors.
    Breast Cancer Research and Treatment 07/2012; 135(1):281-9. · 4.47 Impact Factor
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    ABSTRACT: Study Type - Prognosis inception (cohort) Level of Evidence 2 What's known on the subject? and What does the study add? There are two randomized controlled trials showing that radiotherapy can be beneficial for men with locally advanced prostate cancer. The present study confirms the importance of curative treatment for men with high-risk prostate cancer. OBJECTIVE: •  To investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL. MATERIALS AND METHODS: •  Patients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age ≤75 years were identified in the National Prostate Cancer Register of Sweden. •  Data on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register. •  Following adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis. RESULT: •  A total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria. •  The cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent. •  For the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL. CONCLUSION: •  Treatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL.
    BJU International 07/2012; · 3.05 Impact Factor
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    ABSTRACT: To study the effect of a dietary intervention on acute gastrointestinal side effects and other aspects of health-related quality of life (HRQOL) in prostate cancer patients referred to radiotherapy. A total of 130 patients were randomly assigned to one of two groups: an intervention group (IG, n=64), instructed to reduce their intake of insoluble dietary fibres and lactose, a standard care group (SC, n=66), instructed to continue their normal diet. Gastrointestinal side effects and other aspects of HRQOL were evaluated from baseline up to 2 months after completed radiotherapy, using the EORTC QLQ-C30 and QLQ-PR25 and the study-specific Gastrointestinal Side Effects Questionnaire (GISEQ). A scale indicating adherence to dietary instructions was developed from a Food Frequency Questionnaire (FFQ), with lower scores representing better compliance. Descriptive and inferential statistical analyses were conducted. There was an interaction effect between randomization and time in the FFQ Scores (p<0.001), indicating that both groups followed their assigned dietary instructions. The dietary intervention had no effect on gastrointestinal side effects or other aspects of HRQOL. During radiotherapy, the percentage of patients with bowel symptoms and bloated abdomen was lower in IG compared to SC, but the between-group differences were not statistically significant. During radiotherapy, the percentage of patients with bowel symptoms, urinary symptoms, pain, fatigue and diminished physical and role functioning increased in both groups. The dietary intervention had no effect on gastrointestinal side effects or other aspects of HRQOL. The tendency towards lower prevalence of bowel symptoms in IG may indicate some positive effect of the dietary intervention, but methodological refinements, clearer results and longer follow-up are needed before the value of diet change can be established with certainty.
    Radiotherapy and Oncology 05/2012; 103(3):333-40. · 4.52 Impact Factor
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    ABSTRACT: When diagnosed with breast cancer, most women's lives change as well as their perspectives on and appreciation of life. The aim of the present study was to evaluate whether psychosocial support intervention could influence health-related quality of life (HRQOL) and fatigue during the first year after diagnosis. Of 382 patients with newly diagnosed breast cancer, 191 patients were randomized to an intervention group and 191 patients were randomized to a routine control group. The intervention group received support intervention that lasted 1 week on a residential basis, followed by 4 days of follow-up 2 months later. The support intervention included informative educational parts, relaxation training, mental visualization, and nonverbal communication. HRQOL was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BR23 questionnaires and fatigue with the Norwegian version of the fatigue scale at baseline and at 2, 6, and 12 months after intervention. There was a time-dependent improvement in both functional and symptom scales between baseline and 12 months as measured by the EORTC QLQ-C30 and BR23 questionnaires and there was a decrease in fatigue between baseline and after 2 months with further improvement up to 12 months in both groups, but there were no differences between the intervention and control groups at any point in time. HRQOL improves and symptoms of fatigue decrease over time, but we could not see any additional effect from the rehabilitation program in this setting.
    Supportive Care in Cancer 05/2012; 20(12):3325-34. · 2.09 Impact Factor
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    ABSTRACT: Healthcare professionals have shown concern about performing mouth-to-mouth ventilation due to the risks to themselves with the procedure. However, little is known about healthcare professionals' fears and attitudes to start CPR and the impact of training. To examine whether there were any changes in the attitudes among healthcare professionals to performing CPR from before to after training. Healthcare professionals from two Swedish hospitals were asked to answer a questionnaire before and after training. The questions were relating to physical and mental discomfort and attitudes to CPR. Statistical analysis used was generalized McNemar's test. Overall, there was significant improvement in 10 of 11 items, reflecting various aspects of attitudes to CPR. All groups of health care professionals (physicians, nurses, assistant nurses, and "others" = physiotherapists, occupational therapists, social welfare officers, psychologists, biomedical analysts) felt more secure in CPR knowledge after education. In other aspects, such as anxiety prior to a possible cardiac arrest, only nurses and assistant nurses improved.The concern about being infected, when performing mouth to mouth ventilation, was reduced with the most marked reduction in physicians (75%; P < 0.001). In this hospital-based setting, we found a positive outcome of education and training in CPR concerning healthcare professionals' attitudes to perform CPR. They felt more secure in their knowledge of cardiopulmonary resuscitation. In some aspects of attitudes to resuscitation nurses and assistant nurses appeared to be the groups that were most markedly influenced. The concern of being infected by a disease was low.
    Scandinavian Journal of Trauma Resuscitation and Emergency Medicine 04/2012; 20:26. · 1.68 Impact Factor
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    ABSTRACT: BACKGROUND: Survival after in-hospital cardiac arrest (CA) has been reported to be surprisingly low without any major improvement during the last decade. AIMS: The aim of this study is to evaluate the clinical impact (delay to defibrillation and survival after CA) of an intervention within 1 single hospital (Västerås, Sweden), including (1) a systematic education of all health care professionals in cardiopulmonary resuscitation and (2) the implementation of 18 automated external defibrillators. METHODS: Information was retrieved from the Swedish National Register of Cardiopulmonary Resuscitation. The differences between the 2 calendar periods were evaluated by χ(2) and Fisher exact tests. Logistic regression was used to control for potential confounders. RESULTS: In total, there were 73 in-hospital CAs before (12 months) and 133 after (18 months) the intervention. The overall delay to defibrillation was not reduced after the intervention, and the proportion of survivors to hospital discharge was 26% before and 32% after the intervention (P =.51). Cerebral function, however, was improved after the intervention (as judged by the cerebral performance categories score; P < .001). Thus, the proportion of survivors among all CA patients discharged with a cerebral performance scale score of 1 or 2 (good or acceptable cerebral function) increased from 20% to 32%. CONCLUSION: An intervention within 1 single hospital (systematic training of all health care professionals in cardiopulmonary resuscitation and implementation of automated external defibrillators) did not reduce treatment delay or increase overall survival. Our results, however, suggest indirect signs of an improved cerebral function among survivors.
    The American journal of emergency medicine 03/2012; · 1.54 Impact Factor
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    ABSTRACT: The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.
    International Journal of Cancer 03/2012; 131(10):2264-73. · 6.20 Impact Factor
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    ABSTRACT: Although the central role of the immune system for tumor prognosis is generally accepted, a single robust marker is not yet available. On the basis of receiver operating characteristic analyses, robust markers were identified from a 60-gene B cell-derived metagene and analyzed in gene expression profiles of 1,810 breast cancer; 1,056 non-small cell lung carcinoma (NSCLC); 513 colorectal; and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin-embedded tissue of 330 breast cancer patients. The cell types were identified with immunohistochemical costaining and confocal fluorescence microscopy. We identified immunoglobulin κ C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis-free survival across different molecular subtypes in node-negative breast cancer (n = 965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n = 845; P < 0.001). In addition, IGKC gene expression was prognostic in NSCLC and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin-embedded tissues of 330 breast cancer patients. Tumor-infiltrating plasma cells were identified as the source of IGKC expression. Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anticancer therapy. It could be validated in several independent cohorts and carried out similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.
    Clinical Cancer Research 02/2012; 18(9):2695-703. · 7.84 Impact Factor
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    ABSTRACT: PURPOSE: Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available. EXPERIMENTAL DESIGN: Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy. RESULTS: We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expression CONCLUSION: Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.
    Clinical Cancer Research 02/2012; · 7.84 Impact Factor

Publication Stats

549 Citations
215.05 Total Impact Points

Institutions

  • 2013
    • CUNY Graduate Center
      New York City, New York, United States
    • Technische Universität Dortmund
      Dortmund, North Rhine-Westphalia, Germany
  • 2009–2013
    • Karolinska Institutet
      • • Department of Medical Epidemiology and Biostatistics
      • • Institutionen för onkologi-patologi
      Solna, Stockholm, Sweden
  • 2008–2013
    • Uppsala University Hospital
      • Department of Oncology
      Uppsala, Uppsala, Sweden
    • Odense University Hospital
      • Department of Oncology - R
      Odense, South Denmark, Denmark
  • 2000–2012
    • Uppsala University
      • • Department of Immunology, Genetics and Pathology
      • • Department of Medical Sciences
      Uppsala, Uppsala, Sweden
  • 2011
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
  • 2010
    • Lund University
      • Department of Urology
      Lund, Skane, Sweden
  • 2004
    • Karolinska University Hospital
      • Department of Oncology
      Stockholm, Stockholm, Sweden