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1.
Oncology ; 101(4): 234-239, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36538913

RESUMEN

BACKGROUND/AIM: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare our institute experience with the data existing in the literature. MATERIALS AND METHODS: We included in our analysis 29 patients who received a diagnosis of PBA or SBA between 2006 and 2019. RESULTS: All patients received surgery as frontline treatment, but only 6 patients underwent to adjuvant treatment. Neoadjuvant chemotherapy was administered 2 patients. The preferred chemotherapeutic regimen was taxanes with or without gemcitabine and associated with anthracyclines. A lower median RFS and OS were reported in patients with PBA compared to those with SBA, but the difference observed was not statistically significant. Patients with PBA had a lower median age at the diagnosis (38 vs. 75). CONCLUSION: In our analysis, we have shown a lower median RFS and OS in patients with PBA compared with those with SBA, and a significantly younger age at diagnosis in patients affected by PBA.


Asunto(s)
Neoplasias de la Mama , Hemangiosarcoma , Humanos , Femenino , Hemangiosarcoma/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Antibióticos Antineoplásicos
2.
Mol Cell Proteomics ; 19(2): 245-260, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31792072

RESUMEN

Triple-negative breast cancer (TNBC) is characterized by poor response to therapy and low overall patient survival. Recently, Estrogen Receptor beta (ERß) has been found to be expressed in a fraction of TNBCs where, because of its oncosuppressive actions on the genome, it represents a potential therapeutic target, provided a better understanding of its actions in these tumors becomes available. To this end, the cell lines Hs 578T, MDA-MB-468 and HCC1806, representing the claudin-low, basal-like 1 and 2 TNBC molecular subtypes respectively, were engineered to express ERß under the control of a Tetracycline-inducible promoter and used to investigate the effects of this transcription factor on gene activity. The antiproliferative effects of ERß in these cells were confirmed by multiple functional approaches, including transcriptome profiling and global mapping of receptor binding sites in the genome, that revealed direct negative regulation by ERß of genes, encoding for key components of cellular pathways associated to TNBC aggressiveness representing novel therapeutic targets such as angiogenesis, invasion, metastasis and cholesterol biosynthesis. Supporting these results, interaction proteomics by immunoprecipitation coupled to nano LC-MS/MS mass spectrometry revealed ERß association with several potential nuclear protein partners, including key components of regulatory complexes known to control chromatin remodeling, transcriptional and post-transcriptional gene regulation and RNA splicing. Among these, ERß association with the Polycomb Repressor Complexes 1 and 2 (PRC1/2), known for their central role in gene regulation in cancer cells, was confirmed in all three TNBC subtypes investigated, suggesting its occurrence independently from the cellular context. These results demonstrate a significant impact of ERß in TNBC genome activity mediated by its cooperation with regulatory multiprotein chromatin remodeling complexes, providing novel ground to devise new strategies for the treatment of these diseases based on ligands affecting the activity of this nuclear receptor or some of its protein partners.


Asunto(s)
Colesterol/biosíntesis , Cromatina/metabolismo , Receptor beta de Estrógeno/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Femenino , Perfilación de la Expresión Génica , Humanos , Proteómica , Neoplasias de la Mama Triple Negativas/genética
3.
Int J Mol Sci ; 22(18)2021 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-34576322

RESUMEN

Rare cancers are identified as those with an annual incidence of fewer than 6 per 100,000 persons and includes both epithelial and stromal tumors from different anatomical areas. The advancement of analytical methods has produced an accurate molecular characterization of most human cancers, suggesting a "molecular classification" that has allowed the establishment of increasingly personalized therapeutic strategies. However, the limited availability of rare cancer samples has resulted in very few therapeutic options for these tumors, often leading to poor prognosis. Long non coding RNAs (lncRNAs) are a class of non-coding RNAs mostly involved in tumor progression and drug response. In particular, the lncRNA HOX transcript antisense RNA (HOTAIR) represents an emergent diagnostic, prognostic and predictive biomarker in many human cancers. The aim of this review is to highlight the role of HOTAIR in rare cancers, proposing it as a new biomarker usable in the management of these tumors.


Asunto(s)
Neoplasias/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias/genética , ARN Largo no Codificante/genética
4.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34208964

RESUMEN

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases occurring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.


Asunto(s)
Genes Homeobox , Neoplasias Intestinales/patología , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Intestinales/genética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/genética , Neoplasias Gástricas/genética , Regulación hacia Arriba
5.
Breast J ; 26(5): 860-872, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31886607

RESUMEN

To compare diagnostic performance of contrast-enhanced dual-energy digital mammography (CEDM) and digital breast tomosynthesis (DBT) alone and in combination compared to 2D digital mammography (MX) and dynamic contrast-enhanced MRI (DCE-MRI) in women with breast lesions. We enrolled 100 consecutive patients with breast lesions (BIRADS 3-5 at imaging or clinically suspicious). CEDM, DBT, and DCE-MRI 2D were acquired. Synthetized MX was obtained by DBT. A total of 134 lesions were investigated on 111 breasts of 100 enrolled patients: 53 were histopathologically proven as benign and 81 as malignant. Nonparametric statistics and receiver operating characteristic (ROC) curve were performed. Two-dimensional synthetized MX showed an area under ROC curve (AUC) of 0.764 (sensitivity 65%, specificity 80%), while AUC was of 0.845 (sensitivity 80%, specificity 82%) for DBT, of 0.879 (sensitivity 82%, specificity 80%) for CEDM, and of 0.892 (sensitivity 91%, specificity 84%) for CE-MRI. DCE-MRI determined an AUC of 0.934 (sensitivity 96%, specificity 88%). Combined CEDM with DBT findings, we obtained an AUC of 0.890 (sensitivity 89%, specificity 74%). A difference statistically significant was observed only between DCE-MRI and CEDM (P = .03). DBT, CEDM, CEDM combined to tomosynthesis, and DCE-MRI had a high ability to identify multifocal and bilateral lesions with a detection rate of 77%, 85%, 91%, and 95% respectively, while 2D synthetized MX had a detection rate for multifocal lesions of 56%. DBT and CEDM have superior diagnostic accuracy of 2D synthetized MX to identify and classify breast lesions, and CEDM combined with DBT has better diagnostic performance compared with DBT alone. The best results in terms of diagnostic performance were obtained by DCE-MRI. Dynamic information obtained by time-intensity curve including entire phase of contrast agent uptake allows a better detection and classification of breast lesions.


Asunto(s)
Neoplasias de la Mama , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Medios de Contraste , Femenino , Humanos , Imagen por Resonancia Magnética , Mamografía , Intensificación de Imagen Radiográfica , Sensibilidad y Especificidad
6.
Proc Natl Acad Sci U S A ; 114(29): 7623-7628, 2017 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-28667123

RESUMEN

Obesity and type 2 diabetes are significant risk factors for malignancies, being associated with chronic inflammation and hyperinsulinemia. In this context, insulin can synergize with inflammation to promote proliferation, survival, and dissemination of cancer cells. Point mutation of p53 is a frequent event and a significant factor in cancer development and progression. Mutant p53 protein(s) (mutp53) can acquire oncogenic properties that increase metastasis, proliferation, and cell survival. We report that breast and prostate cancer cells with mutant p53 respond to insulin stimulation by increasing cell proliferation and invasivity, and that such a response depends on the presence of mutp53. Mechanistically, we find that mutp53 augments insulin-induced AKT1 activation by binding and inhibiting the tumor suppressor DAB2IP (DAB2-interacting protein) in the cytoplasm. This molecular axis reveals a specific gain of function for mutant p53 in the response to insulin stimulation, offering an additional perspective to understand the relationship between hyperinsulinemia and cancer evolution.


Asunto(s)
Insulina/metabolismo , Mutación , Proteínas Proto-Oncogénicas c-akt/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Activadoras de ras GTPasa/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Progresión de la Enfermedad , Femenino , Humanos , Hiperinsulinismo/metabolismo , Inflamación , Masculino , Ratones , Proteínas Mutantes/genética , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Riesgo , Proteínas Activadoras de ras GTPasa/antagonistas & inhibidores
7.
Int J Mol Sci ; 21(17)2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32825330

RESUMEN

The estrogen receptor (ER) signaling regulates numerous physiological processes mainly through activation of gene transcription (genomic pathways). Caveolin1 (CAV1) is a membrane-resident protein that behaves as platform to enable different signaling molecules and receptors for membrane-initiated pathways. CAV1 directly interacts with ERs and allows their localization on membrane with consequent activation of ER-non-genomic pathways. Loss of CAV1 function is a common feature of different types of cancers, including breast cancer. Two protein isoforms, CAV1α and CAV1ß, derived from two alternative translation initiation sites, are commonly described for this gene. However, the exact transcriptional regulation underlying CAV1 expression pattern is poorly elucidated. In this study, we dissect the molecular mechanism involved in selective expression of CAV1ß isoform, induced by estrogens and downregulated in breast cancer. Luciferase assays and Chromatin immunoprecipitation demonstrate that transcriptional activation is triggered by estrogen-responsive elements embedded in CAV1 intragenic regions and DNA-binding of estrogen-ER complexes. This regulatory control is dynamically established by local chromatin changes, as proved by the occurrence of histone H3 methylation/demethylation events and association of modifier proteins as well as modification of H3 acetylation status. Thus, we demonstrate for the first time, an estrogen-ERs-dependent regulatory circuit sustaining selective CAV1ß expression.


Asunto(s)
Neoplasias de la Mama/genética , Caveolina 1/genética , Elementos de Respuesta , Adulto , Anciano , Línea Celular Tumoral , Estradiol/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Histonas/genética , Histonas/metabolismo , Humanos , Lisina/metabolismo , Metilación , Persona de Mediana Edad , Receptores de Estrógenos/genética , Elementos de Respuesta/efectos de los fármacos , Elementos de Respuesta/genética
8.
J Cell Physiol ; 234(1): 395-413, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-30132877

RESUMEN

HOX genes are involved with normal development, cell identity, cell differentiation, cell metabolism, apoptosis, autophagy as well as with diseases such as tumor pathogenesis and progression. In particular, the genes belonging to HOX paralogous 13 seem to carry out a relevant role in both tumor development and disease progression. In recent years, several noncoding RNAs (ncRNA) sequences have been identified in HOX loci, including long noncoding RNA (lncRNA) and microRNA (miRNA), highly conserved during evolution. Many studies have shown that specific intergenic ncRNAs in HOX loci could directly modulate HOX genes expression in normal and pathological conditions. In the present review we attempt to describe the role of these ncRNAs, through the regulation of the HOX gene network, in normal cell biology, and, with particular emphasis, in diseases such as in cancer pathogenesis and progression.


Asunto(s)
Genes Homeobox/genética , MicroARNs/genética , Neoplasias/genética , ARN Largo no Codificante/genética , Diferenciación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes/genética , Humanos , Neoplasias/patología
9.
J Cell Physiol ; 232(12): 3422-3432, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28067428

RESUMEN

The molecular mechanisms responsible for the metastatic progression of melanoma have not been fully defined yet. We have recently shown that an important role in this process is certainly played by HOX genes, whose regulation is under control of particular non-coding RNAs, some of which are present within the HOX locus. HOTAIR is the most studied among them, whose aberrant expression is associated with the metastatic progression of many malignancies. The aim of this study was to verify the role played by HOTAIR in metastatic progression of melanoma and to evaluate the circulating levels of HOTAIR in the blood of patients with metastatic melanoma. A series of melanocytic lesions were selected to evaluate the potential changes in the expression of HOTAIR during the evolution of the disease through in situ and molecular approaches. None of the benign melanocytic lesions showed the presence of HOTAIR. The staining of HOTAIR resulted very weak in the primary pT1 lesions, while it was very strong in all pairs of primary tissues and corresponding metastases. Surprisingly, we found the presence of HOTAIR in some intratumoral lymphocytes, while this positivity decreased in lymphocyte component further away from the tumor. HOTAIR was also detected in the serum of selected metastatic patients. These data allowed us to speculate on the fundamental role played by HOTAIR in tumor evolution of melanoma. Its presence in intratumoral lymphocytes might suggest that its involvement in the modulation of tumor microenvironment and the detection in the serum could be used in the management of melanoma patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Melanoma/sangre , ARN Largo no Codificante/sangre , Neoplasias Cutáneas/sangre , Biomarcadores de Tumor/genética , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Metástasis Linfática , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Melanoma/genética , Melanoma/secundario , Persona de Mediana Edad , Estadificación de Neoplasias , ARN Largo no Codificante/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Microambiente Tumoral
10.
Br J Cancer ; 116(11): 1425-1435, 2017 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-28441382

RESUMEN

BACKGROUND: Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in regulating TNBC-dependent angiogenesis was investigated. METHODS: Expression and regulation of the Hh pathway transcription factor glioma-associated oncogene homolog1 protein (GLI1) were studied on the endothelial compartment and on TNBC-initiated angiogenesis. To evaluate the translational relevance of our findings, the combination of paclitaxel with the Smo inhibitor NVP-LDE225 was tested in TNBC xenografted mice. RESULTS: Tissue microarray analysis on 200 TNBC patients showed GLI1 overexpression paired with vascular endothelial growth factor receptor 2 (VEGFR2) expression. In vitro, Hh pathway promotes TNBC progression in an autocrine manner, regulating the VEGF/VEGFR2 loop on cancer cell surface, and in a paracrine manner, orchestrating tumour vascularisation. These effects were counteracted by Smo pharmacological inhibition. In TNBC xenografted mice, scheduling NVP-LDE225 rather than bevacizumab provided a better sustained inhibition of TNBC cells proliferation and endothelial cells organisation. CONCLUSIONS: This study identifies the Hh pathway as one of the main regulators of tumour angiogenesis in TNBC, thus suggesting Hh inhibition as a potential new anti-angiogenic therapeutic option to be clinically investigated in GLI1 overexpressing TNBC patients.


Asunto(s)
Proteínas Hedgehog/metabolismo , Neovascularización Patológica/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/farmacología , Compuestos de Bifenilo/administración & dosificación , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Células Endoteliales/efectos de los fármacos , Femenino , Silenciador del Gen , Proteínas Hedgehog/antagonistas & inhibidores , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células MCF-7 , Proteínas de la Membrana , Ratones , Ratones Desnudos , Persona de Mediana Edad , Trasplante de Neoplasias , Neovascularización Patológica/tratamiento farmacológico , Paclitaxel/administración & dosificación , Piridinas/administración & dosificación , ARN Mensajero/metabolismo , Trombospondina 1/genética , Trombospondina 1/metabolismo , Análisis de Matrices Tisulares , Transfección , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven , Proteína con Dedos de Zinc GLI1/análisis
11.
Breast Cancer Res Treat ; 164(2): 401-410, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28447241

RESUMEN

BACKGROUND: To evaluate the performance of an abbreviated dynamic contrast-enhanced MR imaging (MRI) protocol for breast cancer detection; a comparison with the complete diagnostic protocol has been conducted. METHODS: A retrospective analysis on 508 patients was performed. Abbreviated protocol (AP) included one pre-contrast and the first post-contrast T1-weighted series. Complete protocol (CP) consisted of four post-contrast and one pre-contrast T1-weighted series. Diagnostic performance was assessed for AP and CP. Performance comparison was made using McNemar's test for sensitivity and specificity and Moskowitz and Pepe's method as regards negative predictive value (NPV) and positive predictive value (PPV). AP has been realized in two different ways (AP1 and AP2) and they were compared by means of Cohen's κ. RESULTS: Both CP and AP revealed 206 of 207 cancers. There were no statistically significant differences between AP and CP diagnostic performance (P > 0.05). NPVs of CP and both versions of AP (99.57 vs. 99.56%, P = 0.39), as well as the specificity (77.08 vs. 75.42%, P = 0.18), were substantially equivalent. Relative predictive value method did not reveal the presence of a statistically significant difference between the PPV of CP and both versions of AP (74.91 vs. 73.57%, P = 0.099). Analysis for single lesion confirmed that both CP and AP had equivalent results: CP and AP revealed 280 of 281 malignancies. NPVs of CP and both AP versions, as well as the specificity (P > 0.05), were substantially equivalent. Relative predictive value method did not reveal the presence of a significant difference between the PPV of CP and both AP versions (70.89 vs. 70.18%, P = 0.25; 70.89 vs. 70.00%, P = 0.13). CONCLUSIONS: Abbreviated approach to breast MRI examination reduces the image acquisition and the reading time associated with MR substantially without influencing the diagnostic accuracy (high sensitivity and NPV >99.5%). AP could translate into cost-savings and could enable a higher number of examinations within the same MR session.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Medios de Contraste , Femenino , Humanos , Italia , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
12.
Int J Mol Sci ; 18(2)2017 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-28230773

RESUMEN

Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes) PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs), to define its real prognostic value, optimizing immunohistochemistry method with an "approved for diagnostic assay" antibody. PD-L1 expression directly correlated with proliferation index (Ki-67), glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan-Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS) but not correlated with overall survival (OS). Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.


Asunto(s)
Antígeno B7-H1/metabolismo , Diabetes Mellitus/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/genética , Biomarcadores de Tumor , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Antígeno Ki-67/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Neoplasias de la Mama Triple Negativas/patología , Carga Tumoral , Adulto Joven
13.
Int J Mol Sci ; 17(5)2016 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-27213372

RESUMEN

In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues.


Asunto(s)
Antígeno B7-H1/metabolismo , Inmunohistoquímica/normas , Neoplasias/diagnóstico , Humanos , Inmunohistoquímica/métodos , Neoplasias/metabolismo , Especificidad de Órganos , Sensibilidad y Especificidad
14.
J Cell Physiol ; 230(8): 1708-12, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25510909

RESUMEN

Genomic and trascriptomic profiling has recently contributed details to the characterization of luminal B breast cancer. We explored the contribution of anthropometric, metabolic, and molecular determinants to the multifaceted heterogeneity of this breast cancer subtype, with a specific focus on the association between body mass index (BMI), pre-treatment fasting glucose, hormone receptors, and expression of human epidermal growth factor receptor 2 (HER2). Extensively annotated specimens were obtained from 154 women with luminal B breast cancer diagnosed at two Italian comprehensive cancer centres. Participants' characteristics were descriptively analyzed overall and by HER2 status (positive vs. negative). BMI (<25 vs ≥25), pre-treatment fasting glucose (

Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/biosíntesis , Adulto , Anciano , Antropometría , Glucemia/análisis , Índice de Masa Corporal , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Receptores de Estrógenos/biosíntesis
15.
Int J Mol Sci ; 15(8): 13166-71, 2014 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-25068699

RESUMEN

Granular cell tumor (GCT) is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report details the morphological features of these synchronous lesions highlighting their biological characteristics and suggesting an appropriate follow up.


Asunto(s)
Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal/complicaciones , Carcinoma Ductal/diagnóstico , Tumor de Células Granulares/complicaciones , Tumor de Células Granulares/diagnóstico , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinoma Ductal/diagnóstico por imagen , Carcinoma Ductal/patología , Femenino , Tumor de Células Granulares/diagnóstico por imagen , Tumor de Células Granulares/patología , Humanos , Inmunofenotipificación , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Ultrasonografía
16.
Int J Oncol ; 64(1)2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038050

RESUMEN

Nuclear receptors (NRs) are transcriptional regulators involved in different aspects of normal cell physiology. Their deregulation is associated with aberrant expression, gene mutations and/or epigenetic alterations that can be related to the pathogenesis of various human diseases, and especially in cancer. In particular, a complex genomic network involved in the development and progression of NR­mediated cancer has been highlighted. Advanced genomic technologies have made it possible to understand that the expression of any particular NR in a given cancer subtype is only one component of a larger transcriptional machinery that is controlled by multiple associated NRs and transcription factors. Additionally, their ability to regulate and to be regulated by molecules of non­coding RNAs, microRNAs as well as long non­coding RNAs, is opening new scenarios for understanding the role of NRs in cancer initiation and progression. In the present review, the authors aimed to outline the reciprocal interactions that exist between the main NRs and long non­coding RNAs in different tumor diseases, to suggest new diagnostic biomarkers as well as therapeutic strategies for these tumors.


Asunto(s)
MicroARNs , Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias/genética , MicroARNs/genética , MicroARNs/metabolismo , Receptores Citoplasmáticos y Nucleares/genética
17.
Breast Cancer Res Treat ; 140(3): 527-33, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23893089

RESUMEN

Our aim was to evaluate the surgical impact of preoperative MRI in young patients. We reviewed a single-institution database of 283 consecutive patients below 40 years of age and who were treated for breast cancer. Thirty-seven (13 %) patients who received neoadjuvant chemotherapy were excluded. The remaining 246 patients included 124 (50 %) who preoperatively underwent conventional imaging (CI), i.e., mammography/ultrasonography (CI-group), and 122 (50 %) who underwent CI and dynamic MRI (CI + MRI-group). Pathology of surgical specimens served as a reference standard. Mann-Whitney, χ (2), and McNemar statistics were used. There were no significant differences between groups in terms of age, tumor pathologic subtype, stage, receptor, or nodal status. The mastectomy rate was 111/246 (45 %) overall but was significantly different between groups (46/124, 37 %, for the CI group and 65/122, 53 %, for the CI + MRI group; p = 0.011). Of 122 CI + MRI patients, 46 (38 %) would have undergone mastectomy due to CI alone, while MRI determined 19 additional mastectomies, increasing the mastectomy rate from 38 % to 53 % (p < 0.001). The number of patients with multifocal, multicentric, synchronous, or bilateral cancers was significantly different between groups (10/124, 8 %, for the CI group and 33/122, 27 %, for the CI + MRI group; p < 0.001). In the CI + MRI group, multifocal, multicentric, or synchronous bilateral cancers were detected with mammography in 5/33 (15 %) patients, with ultrasonography in 15/33 (45 %) patients, and with MRI in 32/33 (97 %) patients (p < 0.005). Two mastectomies were due to false positives at both conventional tests in the CI group (2/124, 1.6 %) and two mastectomies were due to MRI false positives in the CI + MRI group (2/122, 1.6 %). In conclusion, breast cancer in young patients was treated with mastectomy in 37-38 % of cases on the basis of CI only and in these patients MRI was more sensitive than CI for multifocal, multicentric, or synchronous bilateral cancers, resulting in an additional mastectomy rate of 15 %. A low probability of inappropriate imaging-based decision-making for mastectomy exists for both CI alone and for CI + MRI, making presurgical needle biopsy mandatory for findings that suggest a need for mastectomy.


Asunto(s)
Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética/métodos , Cuidados Preoperatorios/métodos , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Humanos , Mamografía/métodos , Mastectomía , Estudios Retrospectivos
18.
BMC Cancer ; 13: 15, 2013 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-23305429

RESUMEN

BACKGROUND: Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. METHODS: In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. RESULTS: Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). CONCLUSIONS: Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially.Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology.


Asunto(s)
Neoplasias de la Mama/mortalidad , Adulto , Anciano , Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadísticas no Paramétricas , Análisis de Supervivencia
20.
Transl Cancer Res ; 12(3): 651-657, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37033363

RESUMEN

Background: Non-Hodgkin lymphoma (NHL) of the breast is a rare disease and can occur amongst patients affected by Waldenström's Macroglobulinemia (WM). WM is an indolent B-cell lymphoproliferative disorder with an overall incidence of about 1/100,000 in Europe. Breast imaging is not specific to breast lymphoma that often mimics benign lesions. The diagnosis is based on breast biopsy, the presence of MYD88L265P somatic mutation and immunoglobulin M (IgM) paraprotein detectable in the setting of lymphoplasmacytic infiltration by bone marrow (BM) biopsy. Case Description: A 60-year-old woman with personal and familial history of monoclonal gammopathy of undetermined significance (MGUS) and a lump in her right breast was referred to our hospital. Standard imaging showed round mass with smooth edges. The lump was biopsied and the pathology examination showed lymphoplasmacytic lymphoma (LPL) of the breast which led to final the diagnosis of WM. Conclusions: Lymphoma of the breast is a rare disease, often misdiagnosed because of the lack of specific features at mammogram and ultrasound. Core biopsy is crucial to make diagnosis of breast lymphoma and early diagnosis of WM has been shown to improve overall survival (OS). A comprehensive approach is required in order to assess patients affected by blood disorders presenting with a new breast mass that can lead to diagnosis of breast lymphoma.

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