BACKGROUND: Triple-negative breast carcinomas (TNBC) are a heterogeneous group of tumors with mostly aggressive behaviour and poor prognosis. In association with their aggressive behavior and chemoresistance to treatment, the concept of epithelial-mesenchymal transition (EMT) has come to the fore. CD9 and CD29 proteins are associated with EMT and may play a role in TNBC progression. Our aim was to investigate association of these markers with the lymph node metastasis, tumor grade, proliferative activity, and patient survival. PATIENTS AND METHODS: Our cohort consisted of 66 TNBC patients without neoadjuvant therapy, aged 26-81 years. The pathological tumor stages ranged from pT1b to pT3 and histological grades ranged from II to III, according to the Bloom-Richardson system. Immunohistochemical evaluation of CD9, CD29, E-cadherin, vimentin, androgen receptor and Ki-67 expression was performed semiquantitatively using the H-score. Expression of the proteins was statistically evaluated in relation to the clinicopathological parameters and survival of the patients. RESULTS: We observed lower expression of CD9 in lymph node metastases compared to the primary tumor (P = 0.021). The CD29 expression in primary tumor was significantly lower in patients with lymph node metastases compared to patients without cancer dissemination (P = 0.03). Neither CD9 nor CD29 protein expression was associated with breast cancer-specific survival (BCSS). Lower expression of E-cadherin at the periphery of the primary tumor was associated with worse BCSS (P = 0.038). Neither grade nor the presence of lymph node metastases reached significant association with the BCSS. Lower expression of E-cadherin at the periphery was also associated with higher Ki67 (Rs -0.26) and vimentin (Rs -0.33). CONCLUSION: Decreased protein expression of CD9 and CD29 were associated with lymph node metastasis growth, however, their association with survival was not proved. Lower expression of E-cadherin at the periphery of the primary tumor was associated with high proliferation and poor breast cancer-specific survival.
- Klíčová slova
- CD29, CD9, E-cadherin, epithelial-mesenchymal transition, triple-negative breast cancer,
- MeSH
- antigeny CD9 * metabolismus MeSH
- dospělí MeSH
- epitelo-mezenchymální tranzice * MeSH
- imunohistochemie MeSH
- kadheriny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy * MeSH
- nádorové biomarkery * metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- triple-negativní karcinom prsu * patologie metabolismus mortalita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD9 * MeSH
- CD9 protein, human MeSH Prohlížeč
- kadheriny MeSH
- nádorové biomarkery * MeSH
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.
- Klíčová slova
- juvenile idiopathic arthritis (JIA), recommendation, uveitis,
- MeSH
- dítě MeSH
- juvenilní artritida * komplikace diagnóza terapie MeSH
- lidé MeSH
- mladý dospělý MeSH
- uveitida * diagnóza epidemiologie etiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Evropa MeSH
- Slovenská republika epidemiologie MeSH
E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high-grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c-erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.
- MeSH
- axila MeSH
- duktální karcinom prsu metabolismus MeSH
- imunohistochemie MeSH
- invazivní růst nádoru MeSH
- kadheriny metabolismus MeSH
- lidé MeSH
- lobulární karcinom metabolismus MeSH
- lymfatické metastázy MeSH
- nádory prsu metabolismus patologie MeSH
- prognóza MeSH
- receptor erbB-2 metabolismus MeSH
- receptory pro estrogeny metabolismus MeSH
- receptory progesteronu metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kadheriny MeSH
- receptor erbB-2 MeSH
- receptory pro estrogeny MeSH
- receptory progesteronu MeSH
The aim of our study was to assess the ERBB2 and TOP2A gene status in breast carcinoma tissue using fluorescence in situ hybridization (FISH) and to compare their amplification with immunohistochemistry assay (IHC) of the ERBB2, resp. topoisomerase IIalpha proteins. TOP2A status is important in tailored treatment as topoisomerase IIalpha is the molecular target for topoisomerase IIalpha inhibitors. This study was conducted to determine whether the methods are equivalent in their assessment of TOP2A status and to correlate the genetic findings with basic tumor and disease characteristics. Locus specific ERBB2, TOP2A genes and chromosome 17 centromeres (CEP17) probes were hybridized to 72 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with non-metastatic breast carcinoma (M0). The ERBB2, TOP2A and CEP17 signals were counted and gene numbers per nucleus or per CEP17 were calculated, respectively. Sections were also stained with commercial polyclonal antibody (HercepTestTM), anti-topoisomerase IIalpha monoclonal antibody (clone SWT3D1) and scored for the presence of membrane/nuclear staining. ERBB2 amplification was found in 20.3%, ERBB2 and TOP2A co-amplification was detected in 14.5% of cases. Deletion of the ERBB2/TOP2A gene was found in 1.4/2.8% of sections, respectively. Concordance of FISH and IHC techniques in the evaluation of ERBB2 and TOP2A status was found in 88.4% and 66.7%, respectively. The low concordance of FISH versus IHC in the evaluation of TOP2A status was mainly due to the presence of TOP2A amplified tumors in IHC negative or weakly positive specimens. Topoisomerase IIalpha expression was increased in bigger tumors, although direct correlation with tumor grading was not found. ERBB2 amplification was found in more aggressive breast cancers with grades 2 and 3, respectively. Interestingly, chromosome 17 polysomy was more frequently observed among older women (>55 years), suffering usually from less aggressive disease. Our results confirm the high concordance of the ERBB2 and TOP2A gene co-amplification in breast carcinoma. Differences between FISH and IHC in the case of ERBB2 gene status were found only in IHC 2+ sections as reported in the literature. However, our study points to the importance of FISH examination of TOP2A gene status in all tumors with ERBB2 amplification.
- MeSH
- amplifikace genu MeSH
- antigeny nádorové genetika MeSH
- DNA vazebné proteiny genetika MeSH
- DNA-topoisomerasy typu II genetika MeSH
- dospělí MeSH
- geny erbB-2 * MeSH
- hybridizace in situ fluorescenční * MeSH
- imunohistochemie * MeSH
- karcinom genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu genetika MeSH
- proteiny vázající poly-ADP-ribosu MeSH
- reprodukovatelnost výsledků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antigeny nádorové MeSH
- DNA vazebné proteiny MeSH
- DNA-topoisomerasy typu II MeSH
- proteiny vázající poly-ADP-ribosu MeSH
- TOP2A protein, human MeSH Prohlížeč
