placeholder
and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Proceed order?

Export
Filter
Document type
Language
Year
  • 1
    Language: English
    In: International journal of molecular sciences, 2019-04-02, Vol.20 (8), p.1830
    Description: The granted European patent EP 2 561 890 describes a procedure for an immunological treatment of cancer. It is based on the principles of the HLA-supported communication of implantation and pregnancy. These principles ensure that the embryo is not rejected by the mother. In pregnancy, the placenta, more specifically the trophoblast, creates an interface between the embryo/fetus and the maternal immune system. Trophoblasts do not express the original HLA identification of the embryo/fetus (HLA-A to -DQ), but instead show the non-classical HLA groups E, F, and G. During interaction with specific receptors of NK cells (e.g., killer-immunoglobulin-like receptors (KIR)) and lymphocytes (lymphocyte-immunoglobulin-like receptors (LIL-R)), the non-classical HLA groups inhibit these immunocompetent cells outside pregnancy. However, tumors are known to be able to express these non-classical HLA groups and thus make use of an immuno-communication as in pregnancies. If this occurs, the prognosis usually worsens. This patent describes, in a first step, the profiling of the non-classical HLA groups in primary tumor tissue as well as metastases and recurrent tumors. The second step comprises tailored antibody therapies, which is the subject of this patent. In this review, we analyze the underlying mechanisms and describe the currently known differences between HLA-supported communication of implantation and that of tumors.
    Subject(s): Biochemistry & Molecular Biology ; Physical Sciences ; Chemistry ; Life Sciences & Biomedicine ; Chemistry, Multidisciplinary ; Science & Technology ; Immunotherapy - methods ; Tumor Escape ; Europe ; Humans ; HLA Antigens - immunology ; HLA Antigens - genetics ; Immune System - cytology ; Neoplasms - therapy ; Neoplasms - genetics ; Immune System - metabolism ; Neoplasms - immunology ; Immune System - immunology ; Neoplasms - pathology ; granted European patent ; individualized antibody therapy ; immune evasion ; cancer ; HLA profiling ; Review ; HLA-F ; HLA-G ; HLA-E
    ISSN: 1422-0067
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Language: English
    In: Clinical epigenetics, 2017, Vol.9 (1), p.46-46
    Description: The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary tumor can be used to predict CIMP status of metastatic disease, which is relevant for patient management as well as for understanding the biology of CIMP CRCs. We assessed the CIMP status of 70 pairs of primary CRC and matched metastases using a CRC-specific panel of five markers ( , , , , and ) where CIMP positive was defined as 3/5 positive markers at a percent methylated reference threshold of ≥10%. Concordance was compared using the Fisher's exact test and  〈 0.05 was considered significant. Sixty-nine of the pairs (98.6%) showed concordant CIMP status in the primary tumor and matched metastasis; five (7.0%) of the pairs were concordantly CIMP positive. Only one pair (1.4%) had divergent CIMP status, demonstrating CIMP positivity (4/5 markers positive) in the primary tumor, while the matched metastasis was CIMP negative (0 markers positive). CIMP status is generally concordant between primary CRCs and matched metastases. Thus, CIMP status in the primary tumor is maintained in matched metastases and can be used to inform CIMP-based therapy options for the metastases.
    Subject(s): Suppressor of Cytokine Signaling 1 Protein - genetics ; Basic Helix-Loop-Helix Transcription Factors - genetics ; Colorectal Neoplasms - genetics ; Epigenesis, Genetic ; Humans ; Middle Aged ; Male ; Nerve Tissue Proteins - genetics ; DNA Methylation ; Neoplasm Metastasis ; Phenotype ; Insulin-Like Growth Factor II - genetics ; Core Binding Factor Alpha 3 Subunit - genetics ; CpG Islands ; Adult ; Female ; Aged ; Biomarkers, Tumor - genetics ; Calcium Channels, T-Type - genetics ; Colorectal Neoplasms - pathology ; Medical research ; Pathogenesis ; Colorectal carcinoma ; Colorectal cancer ; Oncology ; Genomes ; Metastasis ; Patients ; Cancer therapies ; Metastases ; Irinotecan ; Chemotherapy ; Colon cancer ; Medical prognosis ; DNA methylation ; Biomarkers ; Mutation ; Insulin-like growth factor II ; Deoxyribonucleic acid--DNA ; Runx3 protein ; CpG islands ; Biomarker ; Metastatic ; CIMP
    ISSN: 1868-7075
    ISSN: 1868-7083
    E-ISSN: 1868-7083
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: SpringerLink Contemporary (1997 - Present)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Histopathology, 2015-09, Vol.67 (3), p.368-377
    Description: Aims Due to the growing number of somatostatin receptor (SSTR) targeting analogues and radiopeptides used for the diagnosis and therapy of neuroendocrine neoplasms (NEN), the assessment of SSTR subtype status has increasingly gained predictive value. In pathology, the SSTR protein levels are detected routinely by immunohistochemistry (IHC); however, a lack of a standardized evaluation system persists. Thus, in the present investigation, three well‐established semi‐quantitative scoring systems [immunoreactive score (IRS), human epidermal growth factor receptor 2 (HER2)/neu score, H score] used commonly for SSTR‐IHC evaluation in NEN were compared. Methods and results A total of 240 formalin‐fixed, paraffin‐embedded tumour samples from 90 patients with bronchopulmonary NEN were examined by IHC and quantitative reverse transcription–polymerase chain reaction (qRT–PCR) for SSTR1, 2A, 3, 4 and 5 expression. Using both methods, SSTR1, 2A and 5 were the most frequently expressed subtypes. For all SSTR subtypes, all three scores correlated well with each other and with qRT–PCR data. However, the IRS was the most meaningful score with the best correlation to mRNA levels. Conclusions Because a unified IHC scoring system for SSTR analysis is needed urgently to optimize the theranostics of NEN, among the scores tested, the IRS seems to be the most suitable according to our results. It provides sufficient accuracy combined with high practicability.
    Subject(s): lung ; immunoreactive score ; H score ; receptors/somatostatin ; HER2/neu score ; neuroendocrine tumours ; immunohistochemistry ; Lung Neoplasms - genetics ; Neuroendocrine Tumors - pathology ; Neuroendocrine Tumors - metabolism ; Bronchial Neoplasms - genetics ; Humans ; Lung Neoplasms - metabolism ; RNA, Messenger - genetics ; Receptor, ErbB-2 - metabolism ; Lung Neoplasms - pathology ; RNA, Messenger - metabolism ; Receptors, Somatostatin - classification ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Neoplasm - metabolism ; Neuroendocrine Tumors - genetics ; Immunohistochemistry - methods ; Receptors, Somatostatin - genetics ; Bronchial Neoplasms - pathology ; Biomarkers, Tumor - metabolism ; RNA, Neoplasm - genetics ; Biomarkers, Tumor - genetics ; Receptors, Somatostatin - metabolism ; Bronchial Neoplasms - metabolism ; Immunohistochemistry ; Comparative analysis ; Tumors
    ISSN: 0309-0167
    E-ISSN: 1365-2559
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Cancer Immunology, Immunotherapy, 2018-03, Vol.67 (3), p.403-412
    Description: Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p 〈 0.0001), CD3/PDL1 (ρ: 0.5728, p 〈 0.0001) and CD3/PD1 (ρ: 0.7005, p 〈 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.
    Subject(s): Immunology ; Prognosis ; Medicine & Public Health ; NMIBC ; Oncology ; Cancer Research ; mRNA ; PD1 ; PDL1 ; Cancer patients ; Messenger RNA ; Patient outcomes ; Analysis ; Oncology, Experimental ; Research ; Bladder cancer ; Formaldehyde ; Cancer
    ISSN: 0340-7004
    E-ISSN: 1432-0851
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Breast cancer research and treatment, 2014-06, Vol.145 (2), p.295-305
    Description: Glycosylation of cellular proteins has important impact on their stability and functional properties, and glycan structures strongly influence cell adhesion. Many enzymes are involved in glycoconjugate synthesis and degradation, but there is only limited information about their role in breast cancer progression. Therefore, we retrieved RNA expression data of 202 glycosylation genes generated by microarray analysis (Affymetrix HG-U133A) in a cohort of 194 mammary carcinomas with long-term follow-up information. After univariate and multivariate Cox regression analysis, genes with independent prognostic value were identified. These were further analysed by Kaplan-Meier analysis and log-rank tests, and their prognostic value was validated in a second cohort of 200 tumour samples from patients without systemic therapy. In our first cohort, we identified 24 genes with independent prognostic value, coding for sixteen anabolic and eight catabolic enzymes. Functionally, these genes are involved in all important glycosylation pathways, namely O-glycosylation, N-glycosylation, O-fucosylation, synthesis of glycosaminoglycans and glycolipids. Eighteen genes also showed prognostic significance in chemotherapy-treated patients. In the second cohort, six of the 24 relevant genes were of prognostic significance (FUT1, FUCA1, POFUT1, MAN1A1, RPN1 and DPM1), whereas a trend was observed for three additional probesets (GCNT4, ST3GAL6 and UGCG). In a stratified analysis of molecular subtypes combining both cohorts, great differences appeared suggesting a predominant role of N-glycosylation in luminal cancers and O-glycosylation in triple-negative ones. Correlations of gene expression with metastases of various localizations point to a role of glycan structures in organ-specific metastatic spread. Our results indicate that various glycosylation reactions influence progression and metastasis of breast cancer and might thus represent potential therapeutic targets.
    Subject(s): Prognosis ; METASTASIS ; SELECTIN LIGANDS ; HYALURONAN ; Glycosylation ; Breast cancer ; COLON-CARCINOMA CELLS ; ADHESION ; THERAPY ; ALPHA-L-FUCOSE ; Glycan genes ; O-GLYCANS ; EXPRESSION ; PROGRESSION ; Microarray analysis ; Medicine & Public Health ; Oncology ; alpha-L-Fucosidase - genetics ; Fucosyltransferases - genetics ; Lymph Nodes - pathology ; Humans ; Gene Expression Regulation, Neoplastic ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Sialyltransferases - genetics ; Mannosyltransferases - genetics ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Enzymes - genetics ; Breast Neoplasms - mortality ; Female ; Mannosidases - genetics ; Biomarkers, Tumor - genetics ; Enzymes - metabolism ; Cohort Studies ; Enzymes ; Glycosaminoglycans ; RNA ; Genes ; Development and progression ; Plant lipids ; Gene expression ; Membrane lipids ; Chemotherapy ; DNA microarrays ; Analysis ; Genetic aspects ; Health aspects ; Cancer
    ISSN: 0167-6806
    E-ISSN: 1573-7217
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: BMC cancer, 2017-02-13, Vol.17 (1), p.124-124
    Description: Proliferation may predict response to neoadjuvant therapy of breast cancer and is commonly assessed by manual scoring of slides stained by immunohistochemistry (IHC) for Ki-67 similar to ER and PgR. This method carries significant intra- and inter-observer variability. Automatic scoring of Ki-67 with digital image analysis (qIHC) or assessment of MKI67 gene expression with RT-qPCR may improve diagnostic accuracy. Ki-67 IHC visual assessment was compared to the IHC nuclear tool (AperioTM) on core biopsies from a randomized neoadjuvant clinical trial. Expression of ESR1, PGR and MKI67 by RT-qPCR was performed on RNA extracted from the same formalin-fixed paraffin-embedded tissue. Concordance between the three methods (vIHC, qIHC and RT-qPCR) was assessed for all 3 markers. The potential of Ki-67 IHC and RT-qPCR to predict pathological complete response (pCR) was evaluated using ROC analysis and non-parametric Mann-Whitney Test. Correlation between methods (qIHC versus RT-qPCR) was high for ER and PgR (spearman´s r = 0.82, p 〈 0.0001 and r = 0.86, p 〈 0.0001, respectively) resulting in high levels of concordance using predefined cut-offs. When comparing qIHC of ER and PgR with RT-qPCR of ESR1 and PGR the overall agreement was 96.6 and 91.4%, respectively, while overall agreement of visual IHC with RT-qPCR was slightly lower for ER/ESR1 and PR/PGR (91.2 and 92.9%, respectively). In contrast, only a moderate correlation was observed between qIHC and RT-qPCR continuous data for Ki-67/MKI67 (Spearman's r = 0.50, p = 0.0001). Up to now no predictive cut-off for Ki-67 assessment by IHC has been established to predict response to neoadjuvant chemotherapy. Setting the desired sensitivity at 100%, specificity for the prediction of pCR (ypT0ypN0) was significantly higher for mRNA than for protein (68.9% vs. 22.2%). Moreover, the proliferation levels in patients achieving a pCR versus not differed significantly using MKI67 RNA expression (Mann-Whitney p = 0.002), but not with qIHC of Ki-67 (Mann-Whitney p = 0.097) or vIHC of Ki-67 (p = 0.131). Digital image analysis can successfully be implemented for assessing ER, PR and Ki-67. IHC for ER and PR reveals high concordance with RT-qPCR. However, RT-qPCR displays a broader dynamic range and higher sensitivity than IHC. Moreover, correlation between Ki-67 qIHC and RT-qPCR is only moderate and RT-qPCR with MammaTyper® outperforms qIHC in predicting pCR. Both methods yield improvements to error-prone manual scoring of Ki-67. However, RT-qPCR was significantly more specific.
    Subject(s): Carcinoma, Ductal, Breast - genetics ; Carcinoma, Lobular - pathology ; Receptors, Estrogen - metabolism ; Prognosis ; Receptor, ErbB-2 - genetics ; Humans ; Receptor, ErbB-2 - metabolism ; Ki-67 Antigen - metabolism ; Receptors, Progesterone - genetics ; Immunoenzyme Techniques ; Breast Neoplasms - metabolism ; Receptors, Progesterone - metabolism ; Carcinoma, Ductal, Breast - drug therapy ; Neoplasm Grading ; Carcinoma, Lobular - genetics ; Carcinoma, Ductal, Breast - pathology ; Female ; Neoadjuvant Therapy ; Carcinoma, Ductal, Breast - metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Estrogen - genetics ; RNA, Messenger - genetics ; Breast Neoplasms - drug therapy ; Randomized Controlled Trials as Topic ; Breast Neoplasms - genetics ; Ki-67 Antigen - genetics ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Breast Neoplasms - pathology ; ROC Curve ; Carcinoma, Lobular - drug therapy ; Carcinoma, Lobular - metabolism ; Neoplasm Staging ; Clinical Trials, Phase II as Topic ; MammaTyper ; Image analysis ; neoadjuvant ; Immunohistochemistry (IHC) ; Prediction ; Pathologic complete response ; Breast cancer ; mRNA ; Ki67 ; RT-qPCR
    ISSN: 1471-2407
    E-ISSN: 1471-2407
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Breast cancer research : BCR, 2018-02-26, Vol.20 (1), p.15-15
    Description: The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer. The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab. Breast cancer CD4, FOXP3, and CXCL13 contents were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and their influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates in the entire cohort and in selected molecular subgroups. Interactions between variables were analyzed using Cox regression. The triple-negative breast cancer (TNBC) subset of the HE10/97 randomized trial was used for confirmation. High CXCL13 was associated with favorable DDFS in univariable analysis, and independently in multivariable analysis (HR 0.44, 95% CI 0.29-0.67, P ≤ 0.001), most strongly in TNBC (HR 0.39, 95% CI 0.19-0.79, P = 0.009). No significant interaction with chemotherapy or trastuzumab administration was detected. Neither tumor CD4 content nor FOXP3 content was associated with DDFS. The favorable prognostic influence of CXCL13 was confirmed in the HE10/97 trial patient population with TNBC (HR 0.30, 95% CI 0.09-0.93; P = 0.038). The results provide a high level of evidence that humoral immunity influences the survival outcomes of patients with early breast cancer, in particular of those with TNBC. The study reports retrospective biomarker analyses in the prospective FinHer trial and the prospective HE10/97 trial. ISRCTN76560285 . Registered on 18 March 2005. ACTRN12611000506998 . Registered on 16 May 2011.
    Subject(s): Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Chemokine CXCL13 - genetics ; Prognosis ; Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Trastuzumab - administration & dosage ; Lymphocytes, Tumor-Infiltrating - drug effects ; Forkhead Transcription Factors - genetics ; Triple Negative Breast Neoplasms - drug therapy ; Vinorelbine - administration & dosage ; Disease-Free Survival ; Docetaxel - administration & dosage ; Triple Negative Breast Neoplasms - genetics ; Chemotherapy, Adjuvant - adverse effects ; Triple Negative Breast Neoplasms - pathology ; Adult ; Female ; Aged ; Biomarkers, Tumor - genetics ; CD4-Positive T-Lymphocytes ; CD4 Antigens - genetics ; Care and treatment ; Lymphocytes ; Analysis ; Breast cancer ; Research ; T cells ; Immune system ; Tumor-infiltrating lymphocytes ; Humoral
    ISSN: 1465-542X
    ISSN: 1465-5411
    E-ISSN: 1465-542X
    Source: BioMedCentral Open Access
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: British journal of cancer, 2018-03-20, Vol.118 (6), p.847-856
    Description: Alterations in protein glycosylation have been related to malignant transformation and tumour progression. We recently showed that low mRNA levels of Golgi alpha-mannosidase MAN1A1 correlate with poor prognosis in breast cancer patients. We analysed the role of MAN1A1 on a protein level using western blot analysis (n=105) and studied the impact of MAN1A1-related glycosylation on the prognostic relevance of adhesion molecules involved in breast cancer using microarray data (n=194). Functional consequences of mannosidase inhibition using the inhibitor kifunensine or MAN1A1 silencing were investigated in breast cancer cells in vitro. Patients with low/moderate MAN1A1 expression in tumours showed significantly shorter disease-free intervals than those with high MAN1A1 levels (P=0.005). Moreover, low MAN1A1 expression correlated significantly with nodal status, grading and brain metastasis. At an mRNA level, membrane proteins ALCAM and CD24 were only significantly prognostic in tumours with high MAN1A1 expression. In vitro, reduced MAN1A1 expression or mannosidase inhibition led to a significantly increased adhesion of breast cancer cells to endothelial cells. Our study demonstrates the prognostic role of MAN1A1 in breast cancer by affecting the adhesive properties of tumour cells and the strong influence of this glycosylation enzyme on the prognostic impact of some adhesion proteins.
    Subject(s): Prognosis ; Antigens, CD - biosynthesis ; Humans ; Middle Aged ; Fetal Proteins - metabolism ; Mannosidases - metabolism ; RNA, Messenger - metabolism ; Antigens, CD - genetics ; Cell Movement - physiology ; Antigens, CD - metabolism ; Breast Neoplasms - metabolism ; Breast Neoplasms - enzymology ; Neoplasm Metastasis ; Female ; Mannosidases - genetics ; Cell Adhesion Molecules, Neuronal - metabolism ; RNA, Messenger - genetics ; Cell Proliferation - physiology ; Kaplan-Meier Estimate ; Survival Rate ; Glycosylation ; Fetal Proteins - biosynthesis ; Blotting, Western ; Cell Adhesion Molecules, Neuronal - genetics ; Disease-Free Survival ; Mannosidases - biosynthesis ; Breast Neoplasms - pathology ; Cell Adhesion - physiology ; Cell Adhesion Molecules, Neuronal - biosynthesis ; Cell Line, Tumor ; Fetal Proteins - genetics ; Apoptosis - physiology ; Molecular Diagnostics ; mannosidase ; metastasis ; breast cancer ; MAN1A1 ; adhesion ; N-glycosylation
    ISSN: 0007-0920
    E-ISSN: 1532-1827
    Source: Nature Open Access
    Source: Nature Journals Online
    Source: PubMed Central
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Breast cancer research and treatment, 2013-01, Vol.137 (1), p.57-67
    Description: High proliferation rates are characteristic of cancer, and proliferation markers make up the majority of genes included in RNA-based prognostic gene signatures applied for breast cancer patients. Based on prior data on differences in molecular subgroups of breast cancer, we hypothesized that the significance of single proliferation markers might differ in luminal, Her2-positive and triple-negative subtypes. Therefore, we compared mRNA expression data of Ki67, TOP2A, and RacGAP1 using a pool of 562 Affymetrix U133A microarrays from breast cancer samples. “Luminal,” “triple-negative,” and “Her2-positive” subcohorts were defined by ESR1 and ERBB2 mRNA expression using pre-defined cut-offs. The analysis of the three potential proliferation markers revealed subtype-specific differences: in luminal carcinomas, expression of all three markers was a significant indictor of early recurrence in univariate and multivariate analysis, but RacGAP1 was superior to Ki67 and TOP2A in significance. In triple-negative tumors, only Ki67 was a significant and independent marker, whereas none of the markers showed a significant prognostic impact in Her2-positive cases. Within the group of luminal carcinomas, the proliferation markers had different impact depending on the treatment of patients: in untreated patients, Ki67, TOP2A, and RacGAP1 were significant and independent prognostic markers. In chemotherapy-treated patients, overexpression of all three markers was predictive for early recurrence, but only RacGAP1 retained significance in multivariate analysis. In contrast, RacGAP1 was the only predictive proliferation marker in the endocrine treatment group. These data point to subtype-specific differences in the relevance of proliferation-associated genes, and RacGAP1 might be a strong prognostic and predictive marker in the luminal subgroup.
    Subject(s): TOP2A ; Medicine & Public Health ; Molecular subgroups ; RacGAP1 ; Oncology ; Breast cancer ; Proliferation ; Ki67 ; Multivariate Analysis ; Carcinoma, Lobular - pathology ; Receptors, Estrogen - metabolism ; Cell Proliferation ; Prognosis ; Humans ; Middle Aged ; Receptor, ErbB-2 - metabolism ; Ki-67 Antigen - metabolism ; GTPase-Activating Proteins - metabolism ; RNA, Messenger - metabolism ; Carcinoma, Ductal, Breast - mortality ; Carcinoma, Lobular - mortality ; Breast Neoplasms - metabolism ; Receptors, Progesterone - metabolism ; Breast Neoplasms - therapy ; DNA-Binding Proteins - metabolism ; Poly-ADP-Ribose Binding Proteins ; Carcinoma, Lobular - therapy ; Aged, 80 and over ; Antigens, Neoplasm - metabolism ; Biomarkers, Tumor - metabolism ; Adult ; Carcinoma, Ductal, Breast - pathology ; Female ; Retrospective Studies ; Carcinoma, Ductal, Breast - metabolism ; Antigens, Neoplasm - genetics ; DNA Topoisomerases, Type II - metabolism ; Gene Expression ; RNA, Messenger - genetics ; Kaplan-Meier Estimate ; Proportional Hazards Models ; Treatment Outcome ; DNA-Binding Proteins - genetics ; Carcinoma, Ductal, Breast - therapy ; Disease-Free Survival ; Ki-67 Antigen - genetics ; Breast Neoplasms - pathology ; Breast Neoplasms - mortality ; DNA Topoisomerases, Type II - genetics ; Aged ; Biomarkers, Tumor - genetics ; Carcinoma, Lobular - metabolism ; GTPase-Activating Proteins - genetics ; Chemotherapy ; RNA ; Analysis ; Cancer
    ISSN: 0167-6806
    E-ISSN: 1573-7217
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Virchows Archiv : an international journal of pathology, 2017-03, Vol.470 (3), p.267-274
    Description: Differential expression of cytokeratins (CK) is a characteristic feature of chemoresistant luminal (KRT20) and chemosensitive intrinsic aggressive basal (KRT5) subtypes in muscle-invasive bladder cancer (MIBC). We investigated mRNA expression of KRT5 and KRT20 and its predictive value in stage pT1 bladder cancer. In retrospective analysis of clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder, a single-step RT-qPCR was used to measure mRNA expression. Furthermore, immunohistochemical (IHC) staining of CK20, panCK, and MIB1 was performed. Valid measurements were obtained from 231 samples out of a series of 284 patients. Spearman correlation revealed significant associations between mRNA and protein expression of KRT20/CK20 (ρ 0.6096, p 〈 0.0001) and MKI67/MIB1 (ρ 0.5467, p 〈 0.0001). A positive correlation was found between MKI67 and KRT20 expression (ρ 0.3492, p 〈 0.0001), while MKI67 and KRT5 were negatively correlated (ρ −0.1693, p = 0.01). High KRT20 expression (≥40.26) was significantly associated with worse recurrence free survival (RFS) (p = 0.001), progression-free survival (PFS) (p = 0.0003), and cancer specific survival (CSS) (p = 0.0414). The combination of high KRT20 expression and low KRT5 expression (〈36.83) was associated with unfavorable RFS (p = 0.0038) and PFS (p = 0.0003) and proved to be the only independent predictor for RFS (p = 0.0055) and PFS (p = 0.0023) in multivariate analysis. KRT20 mRNA determination was superior to CK20 protein estimation with regard to RFS and PFS prediction. KRT20 and KRT5 mRNA quantification can predict recurrence and progression of stage pT1 NMIBC reflecting basal and luminal subtypes of MIBC and is superior to CK20 protein expression determined by IHC.
    Subject(s): Pathology ; Cytokeratin ; Molecular subtypes ; Medicine & Public Health ; NMIBC ; mRNA ; KRT5 ; KRT20 ; Carcinoma, Transitional Cell - mortality ; Immunohistochemistry ; Urinary Bladder Neoplasms - mortality ; Prognosis ; Keratin-5 - biosynthesis ; Biomarkers, Tumor - analysis ; Humans ; Middle Aged ; Kaplan-Meier Estimate ; Proportional Hazards Models ; RNA, Messenger - analysis ; Male ; Reverse Transcriptase Polymerase Chain Reaction ; Neoplasm Recurrence, Local - pathology ; Disease-Free Survival ; Keratin-5 - analysis ; Carcinoma, Transitional Cell - pathology ; Keratin-20 - analysis ; Urinary Bladder Neoplasms - pathology ; Female ; Keratin-20 - biosynthesis ; Aged ; Retrospective Studies ; Keratin ; Messenger RNA ; Bladder cancer ; Analysis ; Formaldehyde
    ISSN: 0945-6317
    E-ISSN: 1432-2307
    Source: Alma/SFX Local Collection
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...