Laboratory for Pathology Oost Nederland

Hengelo, Netherlands

Laboratory for Pathology Oost Nederland

Hengelo, Netherlands
SEARCH FILTERS
Time filter
Source Type

Cuppens T.,Catholic University of Leuven | Annibali D.,Catholic University of Leuven | Coosemans A.,Catholic University of Leuven | Coosemans A.,Leuven Cancer Institute | And 33 more authors.
Clinical Cancer Research | Year: 2017

Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. Experimental Design: We investigated the expression of several druggable targets (phospho-S6S240 ribosomal protein, PTEN, PDGFR-a, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6S240, was tested in patient-derived xenograft (PDX) leiomyosarcoma models. Results: In uterine sarcomas and STUMPs, S6S240 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade (P = 0.001) and recurrence (P = 0.019), as shown by logistic regression. In addition, p-S6240 correlated with shorter progression-free survival (P = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6240 expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6240 in response prediction to PI3K/mTOR inhibition. Conclusions: Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6240 expression is a potential predictive biomarker for response to treatment. © 2017 American Association for Cancer Research.


Jobsen J.J.,Spectrum | van der Palen J.,Spectrum | van der Palen J.,University of Twente | Brinkhuis M.,Laboratory for Pathology Oost Nederland | And 3 more authors.
Breast Cancer Research and Treatment | Year: 2015

The aim of the present study is to look at the mitotic activity index (MAI) as a prognostic factor in a prospective population-based cohort of lymph node-negative invasive breast cancer patients. Analyses were based on 2,048 breast-conserving therapies in 1,971 patients, node-negative, and without any form of adjuvant systemic therapy with long-term follow-up. The 15-year distant metastases-free survival (DMFS) for women ≤55 years was 88.3 % for low MAI values (≤12) versus 73.4 % for high MAI values (>12); (HR 2.8; 95 % CI 1.8–4.4; p < 0.001). Multivariate analyses for DMFS showed significance for MAI. For MAI and Bloom–Richardson grading, by performing a likelihood ratio test, we showed the statistical significance for both. For women >55-years, the MAI was not an independent significant factor. We also confirmed the above findings for disease-specific survival. When multi-gene assays are not available, the MAI remains a robust prognostic marker in women younger than 55 years of age with early node-negative breast cancer. © 2014, Springer Science+Business Media New York.


Jobsen J.J.,Spectrum | Van Der Palen J.,Spectrum | Van Der Palen J.,University of Twente | Baum M.,University College London | And 3 more authors.
British Journal of Cancer | Year: 2013

Background:To investigate the issue of timing of radiation therapy (RT) after lumpectomy in relation to recurrences and outcome.Methods:Analysis was done on 1107 breast-conserving therapies (BCT) with 1070 women, all without lymph node metastasis and without any adjuvant systemic therapy. Timing was defined as time from lumpectomy till RT. Patients were categorised into tertiles: <45 days, 45-56 days, and 57-112 days.Results:Local control did not show a difference between the tertiles. The distant metastasis-free survival as well as the disease-specific survival showed a decreased outcome starting the RT to early after the lumpectomy.Conclusion:The results of this cohort study further refines the hypothesis that timing of RT in BCT might have an impact on outcome. It suggests that a randomised trial in timing of RT in BCT seems necessary to give a definite answer. © 2013 Cancer Research UK.


Jobsen J.J.,Spectrum | Van Der Palen J.,Spectrum | Van Der Palen J.,University of Twente | Brinkhuis M.,Laboratory for Pathology Oost Nederland | And 3 more authors.
Acta Oncologica | Year: 2016

Background. The aim of this study is to analyze the impact of first degree relative (FDR) of young breast cancer patients. Methods. Data were used from our prospective population-based cohort study which started in 1983. The family history (FH) was registered with regard to FDR: the presence or absence of invasive breast cancer in none vs. one or more FDRs at any age. Results. A total of 1109 women, ≤50 years with 1128 breast conserving treatments was seen. The incidence of FDR was 17.0% for one FDR and 3.2% ≥2 FDR. The three groups, none, 1 or ≥2 FDR, were comparable. The local failure rate is comparable for all three groups. Women with a positive FH and metachronous bilateral breast cancer (MBBC) showed a lower local failure (HR 0.2; 95% CI 0.05-0.8). A positive FH was an independent predictor for a better disease-specific survival (HR 0.6; 95% CI 0.4-0.9). Conclusion. A positive FH, based on FDR implies a better prognosis in relation to survival for young women treated with BCT. In contrast to no FH for FDR, MBBC in women with a positive FH was not associated with an increased risk of local recurrence. © 2015 Taylor & Francis.


Jobsen J.,Spectrum | Van Der Palen J.,Spectrum | Van Der Palen J.,University of Twente | Riemersma S.,Laboratory for Pathology Oost Nederland | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2014

Purpose To analyze the incidence and prognostic factors of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) in a large, population-based, single-center study with long-term follow-up. Methods and Materials We analyzed 3595 cases in which BCT was performed in 3824 women with stage I or II breast cancer. The incidence of IBTR was analyzed over time and was based on IBTR as first event. Results The 15-year local relapse-free survival was 90.9%. The hazard estimates for IBTR showed a time course with 2 peaks, the first at approximately 5 years and the second, twice as high, at 12 years. Stratifying subjects by age and margin status showed that, for women ≤40 years old with negative margins, adjuvant systemic therapy led to a 5-fold reduced risk of recurrence compared to none, and the presence of lymph vascular space invasion (LVSI) had a 3-fold increased risk compared to its absence. For women >40 years old, the presence of LVSI (hazard ratio [HR] 2.5) and the presence of lobular carcinoma in situ in the lumpectomy specimen (HR 2.3) were the only 2 risk factors. Conclusions We demonstrated a pattern in risk of IBTR over time, with 2 peaks, first at approximately 5 years and a second, much higher peak at approximately 12 years, especially for women ≤40 years old. For women ≤40 years old with tumor-free resection margins, we noted that the absence of adjuvant systemic therapy and the presence of LVSI were independent prognostic factors of IBTR. For women >40 years old, the presence of LVSI and the presence of lobular carcinoma in situ were independent risk factors. © 2014 Elsevier Inc. All rights reserved.


Jobsen J.J.,Spectrum | Van Der Palen J.,Spectrum | Van Der Palen J.,University of Twente | Brinkhuis M.,Laboratory for Pathology Oost Nederland | And 3 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2012

Purpose: The optimal sequence of radiotherapy and chemotherapy in breast-conserving therapy is unknown. Methods and Materials: From 1983 through 2007, a total of 641 patients with 653 instances of breast-conserving therapy (BCT), received both chemotherapy and radiotherapy and are the basis of this analysis. Patients were divided into three groups. Groups A and B comprised patients treated before 2005, Group A radiotherapy first and Group B chemotherapy first. Group C consisted of patients treated from 2005 onward, when we had a fixed sequence of radiotherapy first, followed by chemotherapy. Results: Local control did not show any differences among the three groups. For distant metastasis, no difference was shown between Groups A and B. Group C, when compared with Group A, showed, on univariate and multivariate analyses, a significantly better distant metastasis-free survival. The same was noted for disease-free survival. With respect to disease-specific survival, no differences were shown on multivariate analysis among the three groups. Conclusion: Radiotherapy, as an integral part of the primary treatment of BCT, should be administered first, followed by adjuvant chemotherapy. © 2012 Elsevier Inc.


PubMed | Laboratory for Pathology Oost Nederland, Leiden University, University of Twente, Spectrum and Ziekenhuis Groep Twente
Type: Journal Article | Journal: International journal of radiation oncology, biology, physics | Year: 2014

To analyze the incidence and prognostic factors of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) in a large, population-based, single-center study with long-term follow-up.We analyzed 3595 cases in which BCT was performed in 3824 women with stage I or II breast cancer. The incidence of IBTR was analyzed over time and was based on IBTR as first event.The 15-year local relapse-free survival was 90.9%. The hazard estimates for IBTR showed a time course with 2 peaks, the first at approximately 5 years and the second, twice as high, at 12 years. Stratifying subjects by age and margin status showed that, for women 40 years old with negative margins, adjuvant systemic therapy led to a 5-fold reduced risk of recurrence compared to none, and the presence of lymph vascular space invasion (LVSI) had a 3-fold increased risk compared to its absence. For women >40 years old, the presence of LVSI (hazard ratio [HR] 2.5) and the presence of lobular carcinoma in situ in the lumpectomy specimen (HR 2.3) were the only 2 risk factors.We demonstrated a pattern in risk of IBTR over time, with 2 peaks, first at approximately 5 years and a second, much higher peak at approximately 12 years, especially for women 40 years old. For women 40 years old with tumor-free resection margins, we noted that the absence of adjuvant systemic therapy and the presence of LVSI were independent prognostic factors of IBTR. For women >40 years old, the presence of LVSI and the presence of lobular carcinoma in situ were independent risk factors.

Loading Laboratory for Pathology Oost Nederland collaborators
Loading Laboratory for Pathology Oost Nederland collaborators