المؤلفون: Heerma van Voss, Marise R., Schrijver, Willemijne A M E, Ter Hoeve, Natalie D., Hoefnagel, Laurien D., Manson, Quirine F., van der Wall, Elsken, Raman, Venu, van Diest, Paul J., Dutch Distant Breast Cancer Metastases Consortium, Distant Breast Cancer Metastases Consortium

المساهمون: Pathologie patiënten zorg, UMC Utrecht, Cancer, Cancer Center Patiëntenzorg, Trialsecretariaat Medische Oncologie

مصطلحات موضوعية: Brain metastasis, Breast cancer, DDX3, DDX3X, DEAD box RNA helicases, Metastasis, Oncology, Cancer Research, Journal Article, Research Support, Non-U.S. Gov't

الوصف: Metastatic breast cancer remains one of the leading causes of death in women and identification of novel treatment targets is therefore warranted. Functional studies showed that the RNA helicase DDX3 promotes metastasis, but DDX3 expression was never studied in patient samples of metastatic cancer. In order to validate previous functional studies and to evaluate DDX3 as a potential therapeutic target, we investigated DDX3 expression in paired samples of primary and metastatic breast cancer. Samples from 79 breast cancer patients with distant metastases at various anatomical sites were immunohistochemically stained for DDX3. Both cytoplasmic and nuclear DDX3 expression were compared between primary and metastatic tumors. In addition, the correlation between DDX3 expression and overall survival was assessed. Upregulation of cytoplasmic (28%; OR 3.7; p = 0.002) was common in breast cancer metastases, especially in triple negative (TN) and high grade cases. High cytoplasmic DDX3 levels were most frequent in brain lesions (65%) and significantly correlated with high mitotic activity and triple negative subtype. In addition, worse overall survival was observed for patients with high DDX3 expression in the metastasis (HR 1.79, p = 0.039). Overall, we conclude that DDX3 expression is upregulated in distant breast cancer metastases, especially in the brain and in TN cases. In addition, high metastatic DDX3 expression correlates with worse survival, implying that DDX3 is a potential therapeutic target in metastatic breast cancer, in particular in the clinically important group of TN patients.

وصف الملف: image/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/351258Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/351258Test

المؤلفون: Schrijver, Willemijne A.M.E., Schuurman, Karianne G., Van Rossum, Annelot, Peeters, Ton, Hoeve, Natalie Ter, Zwart, Wilbert, van Diest, Paul J., Moelans, Cathy B., Dutch Distant Breast Cancer Metastases Consortium

المساهمون: Pathologie mortuarium en obductie, Pathologie, Cancer

مصطلحات موضوعية: Breast cancer, Distant metastases, Effusions, Receptor conversion, Oncology, Journal Article

الوصف: Discordance in estrogen receptor alpha (ERa), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive. We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization. Data were coupled to clinical variables and treatment history. ERa, PR and AR receptor status converted from positive in the primary tumor to negative in the effusion metastases or vice versa in 25-30%, 30-35% and 46-51% of cases for the 1% and 10% thresholds for positivity, respectively. 19-25% of patients converted clinically relevant from "ERa+ or PR+" to ERa-/PR- and 3-4% from ERa-/PR- to "ERa+ or PR+". For HER2, conversion was observed in 6% of cases. Importantly, receptor conversion for ERa (p = 0.058) and AR (p < 0.001) was more often seen in patients adjuvantly treated with endocrine therapy. Analogous to this observation, HER2-loss was more frequent in patients adjuvantly treated with trastuzumab (p < 0.001). Alike solid distant metastases, receptor conversion for ERa, PR, AR and HER2 is a frequent phenomenon in peritoneal and pleural effusion metastases. Adjuvant endocrine and trastuzumab therapy imposes an evolutionary selection pressure on the tumor, leading to receptor loss in effusion metastases. Determination of receptor status in malignant effusion specimens will facilitate endocrine treatment decisionmaking at this lethal state of the disease, and is hence recommended whenever possible.

وصف الملف: image/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/355883Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/355883Test

المؤلفون: Jiwa, Laura S, van Diest, Paul J, Hoefnagel, Laurien D, Wesseling, Jelle, Wesseling, Pieter, Dutch Distant Breast Cancer Metastases Consortium, Moelans, Cathy B

مصطلحات موضوعية: Claudin-4, CAIX, GLUT-1, Receptor conversion, Breast cancer

الوصف: Background Several studies have shown that the immunophenotype of distant breast cancer metastases may differ significantly from that of the primary tumor, especially with regard to differences in the level of hormone receptor protein expression, a process known as receptor conversion. This study aimed to compare expression levels of several membrane proteins between primary breast tumors and their corresponding distant metastases in view of their potential applicability for molecular imaging and drug targeting. Methods Expression of Claudin-4, EGFR, CAIX, GLUT-1 and IGF1R was assessed by immunohistochemistry on tissue microarrays composed of 97 paired primary breast tumors and their distant (non-bone) metastases. Results In both the primary cancers and the metastases, Claudin-4 was most frequently expressed, followed by GLUT-1, CAIX and EGFR. From primary breast cancers to their distant metastases there was positive to negative conversion, e.g. protein expression in the primary tumor with no expression in its paired metastasis, in 6%, 19%, 12%, 38%, and 0% for Claudin-4 (n.s), GLUT-1 (n.s), CAIX (n.s), EGFR (n.s) and IGF1R (n.s) respectively. Negative to positive conversion was seen in 65%, 47%, 43%, 9% and 0% of cases for Claudin-4 (p = 0.049), GLUT-1 (p = 0.024), CAIX (p = 0.002), EGFR (n.s.) and IGF1R (n.s.) respectively. Negative to positive conversion of Claudin-4 in the metastasis was significantly associated with tumor size (p = 0.015), negative to positive conversion of EGFR with negative PR status (p = 0.046) and high MAI (p = 0.047) and GLUT-1 negative to positive conversion with (neo)adjuvant chemotherapy (p = 0.039) and time to metastasis formation (p = 0.034). CAIX and GLUT-1 expression in the primary tumor were significantly associated with high MAI (p = 0.008 and p = 0.038 respectively). Conclusion Claudin-4 is frequently expressed in primary breast cancers but especially in their metastases and is thereby an attractive membrane bound molecular imaging and drug target. Conversion in ...

العلاقة: http://www.biomedcentral.com/1471-2407/14/864Test

الإتاحة: http://www.biomedcentral.com/1471-2407/14/864Test

المؤلفون: Hoefnagel, L. D. C., van der Groep, P., van de Vijver, M. J., Boers, J. E., Wesseling, P., Wesseling, J., Dutch Distant Breast Cancer Metastases Consortium, van der Wall, E., van Diest, P. J.

مصطلحات موضوعية: Original article

الوصف: Background We studied discordance in estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between multiple distant metastases from the same breast cancer patient. Material and methods Multiple distant metastases from 55 female patients were stained for ERα, PR and HER2 by immunohistochemistry and in situ hybridization for confirmation of the HER2 status. Results Different metastatic sites within the same patient showed discordance in ERα receptor status in 7.3% or 10.9% of patients (using a 10% or 1% threshold for positivity, respectively). For PR, 29.1% or 30.9% of patients showed discordance. Taking ERα and PR together, 36.4% of cases (both thresholds) showed discrepancy between metastases. In 10.9% (10% threshold) or 14.5% of patients (1% threshold), such discordance could have clinical consequences with regard to hormonal treatment. For HER2, there was 3.6% discordance on the immunohistochemical level but 0% on the gene level. Conclusion In a significant proportion of metastatic breast cancer patients, discordance in ERα and PR receptor status between different metastatic sites was observed. This implies that multiple metastases may need to be biopsied to optimally reassess receptors.

وصف الملف: text/html

العلاقة: http://annonc.oxfordjournals.org/cgi/content/short/mdt390v1Test; http://dx.doi.org/10.1093/annonc/mdt390Test

الإتاحة: https://doi.org/10.1093/annonc/mdt390Test
http://annonc.oxfordjournals.org/cgi/content/short/mdt390v1Test

المؤلفون: Heerma van Voss, Marise R., Schrijver, Willemijne A M E, Ter Hoeve, Natalie D., Hoefnagel, Laurien D., Manson, Quirine F., van der Wall, Elsken, Raman, Venu, van Diest, Paul J., Dutch Distant Breast Cancer Metastases Consortium, Distant Breast Cancer Metastases Consortium

المساهمون: Targeted Gynaecologic Oncology (TARGON)

المصدر: Clinical & Experimental Metastasis, 34(1), 85–92. Springer Netherlands
Clinical & Experimental Metastasis, 34(1), 85-92. SPRINGER
Clinical & Experimental Metastasis

مصطلحات موضوعية: 0301 basic medicine, CA15-3, Oncology, Cancer Research, PROTEIN, Triple Negative Breast Neoplasms, DEAD box RNA helicases, Metastasis, DEAD-box RNA Helicases, 0302 clinical medicine, Breast cancer, Surgical oncology, Neoplasm Metastasis, Non-U.S. Gov't, Brain Neoplasms, Research Support, Non-U.S. Gov't, INHIBITOR, General Medicine, Prognosis, Metastatic breast cancer, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, DDX3X, Female, Research Paper, medicine.medical_specialty, BRAIN METASTASES, REQUIREMENT, Research Support, Disease-Free Survival, 03 medical and health sciences, Internal medicine, MOTILITY, DDX3, medicine, Journal Article, Humans, THERAPEUTIC TARGET, IDENTIFICATION, business.industry, MUTATIONS, Brain metastasis, Cancer, RNA HELICASE DDX3, medicine.disease, 030104 developmental biology, CELLS, business

الوصف: Metastatic breast cancer remains one of the leading causes of death in women and identification of novel treatment targets is therefore warranted. Functional studies showed that the RNA helicase DDX3 promotes metastasis, but DDX3 expression was never studied in patient samples of metastatic cancer. In order to validate previous functional studies and to evaluate DDX3 as a potential therapeutic target, we investigated DDX3 expression in paired samples of primary and metastatic breast cancer. Samples from 79 breast cancer patients with distant metastases at various anatomical sites were immunohistochemically stained for DDX3. Both cytoplasmic and nuclear DDX3 expression were compared between primary and metastatic tumors. In addition, the correlation between DDX3 expression and overall survival was assessed. Upregulation of cytoplasmic (28%; OR 3.7; p = 0.002) was common in breast cancer metastases, especially in triple negative (TN) and high grade cases. High cytoplasmic DDX3 levels were most frequent in brain lesions (65%) and significantly correlated with high mitotic activity and triple negative subtype. In addition, worse overall survival was observed for patients with high DDX3 expression in the metastasis (HR 1.79, p = 0.039). Overall, we conclude that DDX3 expression is upregulated in distant breast cancer metastases, especially in the brain and in TN cases. In addition, high metastatic DDX3 expression correlates with worse survival, implying that DDX3 is a potential therapeutic target in metastatic breast cancer, in particular in the clinically important group of TN patients. Electronic supplementary material The online version of this article (doi:10.1007/s10585-016-9832-8) contains supplementary material, which is available to authorized users.

وصف الملف: image/pdf; application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::226fe1a2129c071a0618870083853ddeTest