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INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.
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Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC.
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Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Patologistas , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Mama , ConsensoRESUMO
This work explores the complex field of HER2 testing in the HER2-low breast cancer era, with a focus on methodological aspects. We aim to propose clear positions to scientific societies, institutions, pathologists, and oncologists to guide and shape the appropriate diagnostic strategies for HER2-low breast cancer. The fundamental question at hand is whether the necessary tools to effectively translate our knowledge about HER2 into practical diagnostic schemes for the lower spectrum of expression are available. Our investigation is centered on the significance of distinguishing between an immunohistochemistry (IHC) score 0 and score 1+ in light of the clinical implications now apparent, as patients with HER2-low breast cancer become eligible for trastuzumab-deruxtecan treatment. Furthermore, we discuss the definition of HER2-low beyond its conventional boundaries and assess the reliability of established diagnostic procedures designed at a time when therapeutic perspectives were non-existent for these cases. In this regard, we examine potential complementary technologies, such as gene expression analysis and liquid biopsy. Ultimately, we consider the potential role of artificial intelligence (AI) in the field of digital pathology and its integration into HER2 testing, with a particular emphasis on its application in the context of HER2-low breast cancer.
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Inteligência Artificial , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Reprodutibilidade dos Testes , PatologistasRESUMO
Neoadjuvant therapy (NAT) in breast cancer is administered to downstage the tumor, de-escalate surgery, and provide prognostic information that can be used to tailor subsequent adjuvant therapy. In this respect, the pathological evaluation of both pre-NAT biopsies and post-NAT surgical specimens is crucial to precisely assess the treatment response. With the increasing possibilities of NAT protocols and the rising number of eligible patients, it has become extremely important to standardize the pathological response assessment. Here, we provide an update on the recommendations of the Italian Group for the Study of Breast Pathology - the Italian Society of Pathology (GIPaM-SIAPeC) for the analysis of breast cancer samples before and after NAT.
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Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , PrognósticoRESUMO
Pathologic evaluation of early breast cancer after neoadjuvant therapy is essential to provide prognostic information based on tumor response to treatment (pathologic complete response [pCR] or non-pCR) and to inform therapy decisions after surgery. To harmonize the pathologist's handling of surgical specimens after neoadjuvant therapy, a panel of experts in breast cancer convened to developed a consensus on six main topics: (1) definition of pCR, (2) required clinical information, (3) gross examination and sampling, (4) microscopic examination, (5) evaluation of lymph node status, and (6) staging of residual breast tumor. The resulting consensus statements reported in this document highlight the role of an accurate evaluation of tumor response and define the minimum requirements to standardize the assessment of breast cancer specimens after neoadjuvant therapy.
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Neoplasias da Mama , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Prognóstico , Manejo de Espécimes/métodosRESUMO
OBJECTIVES: Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients. METHODS: Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line. RESULTS: Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells. CONCLUSION: SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.
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Translocação Bacteriana , Íleo/imunologia , Doenças Inflamatórias Intestinais/complicações , Mucosa Intestinal/imunologia , Espondilartrite/microbiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Proteínas de Ligação a Ácido Graxo/sangue , Humanos , Íleo/metabolismo , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/metabolismo , Receptores de Lipopolissacarídeos/sangue , Lipopolissacarídeos/sangue , Monócitos/metabolismo , Osteoblastos/metabolismo , Espondilartrite/sangue , Espondilartrite/imunologiaRESUMO
Cancer therapy is limited, in part, by lack of specificity. Thus, identifying molecules that are selectively expressed by, and relevant for, cancer cells is of paramount medical importance. Here, we show that peptidyl-prolyl-cis-trans-isomerase (PPIase) FK506-binding protein 10 (FKBP10)-positive cells are present in cancer lesions but absent in the healthy parenchyma of human lung. FKBP10 expression negatively correlates with survival of lung cancer patients, and its downregulation causes a dramatic diminution of lung tumor burden in mice. Mechanistically, our results from gain- and loss-of-function assays show that FKBP10 boosts cancer growth and stemness via its PPIase activity. Also, FKBP10 interacts with ribosomes, and its downregulation leads to reduction of translation elongation at the beginning of open reading frames (ORFs), particularly upon insertion of proline residues. Thus, our data unveil FKBP10 as a cancer-selective molecule with a key role in translational reprogramming, stem-like traits, and growth of lung cancer.
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Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Biossíntese de Proteínas , Proteínas de Ligação a Tacrolimo/metabolismo , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Peptidilprolil Isomerase/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ribossomos/metabolismoRESUMO
INTRODUCTION: A reliable risk stratification on the basis of tumor biology and host factors of HER2-positive (HER2+) early breast cancer (eBC) patients is needed. The aim of our study was to assess the prognostic role of body mass index (BMI) and hormone receptor (HR) expression in this setting. PATIENTS AND METHODS: We retrospectively evaluated 238 women with stage I to III HER2+ breast cancer who completed adjuvant chemotherapy (CHT) and 1 year of treatment with trastuzumab. The end point was 3-year distant disease-free survival (3yDDFS). Survival analysis was evaluated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional-hazards model adjusting for HR status, BMI, tumor staging, size, nodal status, and type of adjuvant CHT. Association among categorical variables was assessed using χ2 test. RESULTS: The early recurrence rate after 3 years resulted as 4.2% (40% HR+ patients and 60% HR- patients). Neither HR status nor BMI alone showed an association with 3yDDFS in multivariate analysis. However, the hazard ratios for patients with HR- tumors who had also BMI ≥25 (3yDDFS 86.9%; 95% confidence interval [CI], 75.0%-97.7%) were amplified compared with patients with HR+ tumors and with BMI <25 (3yDDFS 98%; 95% CI, 94.8%-100.0%) and other subgroups (P = .003). This observation was confirmed in multivariate analysis (hazard ratio, 1.79; 95% CI, 1.04-3.07; P = .03). CONCLUSION: Our real-life data highlight a different risk of eBC recurrence after grouping patients according to HR status and BMI. These results might help clinicians to identify correct treatment strategies. Patients who are HR- and have BMI ≥25 might benefit from escalation approaches, whereas those who are HR+ and have BMI <25 might be eligible for a shorter duration of adjuvant treatment with anti-HER2 agents.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Índice de Massa Corporal , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Tempo , Trastuzumab/uso terapêutico , Adulto JovemRESUMO
Metastases involving the clivus and craniocervical junction (CCJ) are extremely rare. Skull base involvement can result in cranial nerve palsies, while an extensive CCJ involvement can lead to spinal instability. We describe an unusual case of clival and CCJ metastases presenting with VI cranial nerve palsy and neck pain secondary to CCJ instability from metastatic bladder urothelial carcinoma. The patient was first treated with an endoscopic endonasal approach to the clivus for decompression of the VI cranial nerve and then with occipitocervical fixation and fusion to treat CCJ instability. At the 6-month follow-up, the patient experienced complete recovery of VI cranial nerve palsy. To the best of our knowledge, the simultaneous involvement of the clivus and the CCJ due to metastatic bladder carcinoma has never been reported in the literature. Another peculiarity of this case was the presence of both VI cranial nerve deficit and spinal instability. For this reason, the choice of treatment and timing were challenging. In fact, in case of no neurological deficit and spinal stability, palliative chemo- and radiotherapy are usually indicated. In our patient, the presence of progressive diplopia due to VI cranial nerve palsy required an emergent surgical decompression. In this scenario, the extended endoscopic endonasal approach was chosen as a minimally invasive approach to decompress the VI cranial nerve. Posterior occipitocervical stabilization is highly effective in avoiding patient's neck pain and spinal instability, representing the approach of choice.
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OBJECTIVE: Assess the correlation between MRI characteristics of invasive breast cancer and tumor prognostic features. MATERIALS AND METHODS: 95 women with invasive breast cancer underwent pre-treatment MR. Morphological findings and quantitative ADC were retrospectively evaluated. RESULTS: Smaller size, round shape, spiculated margins and homogeneous internal enhancement pattern on dynamic MRI were independently associated with established predictors of good prognosis, while larger size and rim enhancement pattern were related to predictors of poor prognosis. A positive correlation was observed between ADC value and clinical stage. CONCLUSIONS: MRI may be a useful tool for breast cancer aggressiveness prediction and for guiding subsequent clinical-therapeutic management.
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Neoplasias da Mama/patologia , Mama/patologia , Imageamento por Ressonância Magnética , Adulto , Idoso , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Lung cancer seems to have different epidemiological, biomolecular and clinical characteristics in females than in males, with a better prognosis for women. The aim of the study is to determine gender differences in lung adenocarcinoma in terms of androgen (AR), estrogen (ER)α and progesterone (PgR) receptors expression and their impact on outcome. RESULTS: Overall survival was significantly better in ERα and in PgR positive lung adenocarcinoma patients (median survival 45 vs. 19 months).Eight out of 62 patients showed positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively). There was a significant difference in survival between patients with vs. without c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median survival was greater in positive expression of c-AR than for women with negative c-AR (45 vs. 21 months). MATERIALS AND METHODS: We conducted an analysis on a cohort of 62 patients with advanced NSCLC treated at our institution. We investigated the immunohistochemical expression of n/c AR, ERα and PgR in 62 NSCLC and we correlated it with patients' clinic-pathologic characteristics and with prognosis. CONCLUSIONS: Our results showed that the positive expression of one hormonal receptor could represent a prognostic factor.Furthermore our study suggests that AR should become object of close examination in a larger series of lung adenocarcinoma patients, also for selection of the patients with best prognosis that can perform more chemotherapy lines.
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Adenocarcinoma/química , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/química , Receptor alfa de Estrogênio/análise , Disparidades nos Níveis de Saúde , Neoplasias Pulmonares/química , Receptores Androgênicos/análise , Receptores de Progesterona/análise , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Núcleo Celular/química , Citosol/química , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of the present study was to evaluate the effects of delayed antifungal therapy on the outcome of invasive aspergillosis due to Aspergillus fumigatus in experimental models of infection. METHODS: A clinical isolate of A. fumigatus susceptible to amphotericin B (MIC 0.5 mg/L) and micafungin [minimum effective concentration (MEC) 0.03 mg/L] was used in all experiments. Two models of infection were investigated in immunosuppressed mice: disseminated infection and pulmonary infection. Twenty-four hours (early therapy) and 48 h (delayed therapy) post-infection, the mice were given vehicle, liposomal amphotericin B, micafungin or liposomal amphotericin B plus micafungin (combination). Drug efficacy was assessed by either survival or tissue burden experiments. RESULTS: In disseminated infection, any drug regimen given early significantly prolonged survival. When therapy was delayed, only micafungin and the combination were effective. In pulmonary infection, although there was a trend towards a prolongation of survival of mice treated early with liposomal amphotericin B, only the combination was effective. Similarly, when therapy was delayed, only the combination was effective. In disseminated infection, any drug regimen given early was effective at reducing the cfu in kidney tissue. In pulmonary infection, only liposomal amphotericin B and the combination given early were effective at reducing the cfu in lung tissue. Conversely, when therapy was delayed, no regimen was effective at reducing the tissue burden, regardless of the type of infection. CONCLUSIONS: Our data indicate that delayed initiation of antifungal therapy is deleterious in experimental models of invasive aspergillosis. A combination regimen seems to have some advantages over a single-drug approach when the therapy is started late.
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Antifúngicos/administração & dosagem , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Fatores de Tempo , Anfotericina B/administração & dosagem , Anfotericina B/farmacologia , Animais , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Quimioterapia Combinada , Equinocandinas/administração & dosagem , Equinocandinas/farmacologia , Feminino , Lipopeptídeos/administração & dosagem , Lipopeptídeos/farmacologia , Pulmão/microbiologia , Micafungina , Camundongos , Testes de Sensibilidade Microbiana , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: There is a growing body of evidence that immune response plays a large role in cancer outcome. The neutrophil to lymphocyte ratio (NLR) has been used as a simple parameter of systemic inflammation in several tumors. The purpose was to investigate the association between pre-treatment NLR, disease-free survival and overall survival in patients with early triple negative breast cancer (TNBC). METHODS: We reviewed the records of patients with stage I-III TNBC at our Institution from 2006 to 2012. The association between pre-treatment NLR and survival was analyzed. The difference among variables was calculated by chi-square test. DFS and OS were estimated using Kaplan-Meier method. Cox analysis was performed to analyze clinical parameters for their prognostic relevance. RESULTS: A total of 90 patients were eligible. There was no significant correlation among pre-treatment NLR and various clinical pathological factors. Patients with NLR higher than 3 showed significantly lower DFS (p = 0.002) and OS (p = 0.009) than patients with NLR equal or lower than 3. The Cox proportional multivariate hazard model revealed that higher pre-treatment NLR was independently correlated with poor DFS and OS, with hazard ratio 5.15 (95% confidence interval [CI] 1.11-23.88, p = 0.03) and 6.16 (95% CI 1.54-24.66, p = 0.01) respectively. CONCLUSION: Our study suggests that pre-treatment NLR may be associated with DFS and OS patients with early TNBC. Further validation and a feasibility study are required before it can be considered for clinical use.
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Carcinoma Ductal de Mama/imunologia , Linfócitos/imunologia , Neutrófilos/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Adulto , Idoso , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/terapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Contagem de Linfócitos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Dietary effects on tumor biology can be exploited to unravel cancer vulnerabilities. Here, we present surprising evidence for anti-proliferative action of high-calorie-diet (HCD) feeding on KRAS-driven lung tumors. Tumors of mice that commenced HCD feeding before tumor onset displayed defective unfolded protein response (UPR) and unresolved endoplasmic reticulum (ER) stress. Unresolved ER stress and reduced proliferation are reversed by chemical chaperone treatment. Whole-genome transcriptional analyses revealed FKBP10 as one of the most downregulated chaperones in tumors of the HCD-pre-tumor-onset group. FKBP10 downregulation dampens tumor growth in vitro and in vivo. Providing translational value to these results, we report that FKBP10 is expressed in human KRAS-positive and -negative lung cancers, but not in healthy parenchyma. Collectively, our data shed light on an unexpected anti-tumor action of HCD imposed before tumor onset and identify FKBP10 as a putative therapeutic target to selectively hinder lung cancer.
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Dieta , Neoplasias Pulmonares/patologia , Fenilbutiratos/toxicidade , Proteínas ras/metabolismo , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/efeitos dos fármacos , Regulação para Baixo , Doxiciclina/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos SCID , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a Tacrolimo/antagonistas & inibidores , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Transplante Heterólogo , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Proteínas ras/genéticaRESUMO
BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration is routinely used in the diagnostic work up of pancreatic cancer but has a low sensitivity. Studies showed that Pancreatic Duodenal Homeobox-1 (PDX-1) is expressed in pancreatic cancer, which is associated with a worse prognosis. We aimed to verify whether the assessment of PDX-1 in endoscopic ultrasound-guided fine needle aspiration samples may be helpful for the diagnosis of pancreatic cancer. METHODS: mRNA of 54 pancreatic cancer and 25 cystic lesions was extracted. PDX-1 expression was assessed by Real-Time PCR. RESULTS: In all but two patients with pancreatic cancer, PDX-1 was expressed and was found positive in 7 patients with pancreatic cancer in which cytology was negative. The positivity was associated with a probability of 0.98 (95% CI 0.90-1.00) of having cancer and the negativity with one of 0.08 (95% CI 0.01-0.27). The probability of cancer rose to 1.00 (95% CI 0.97-1.00) for patients positive to both PDX-1 and cytology and fell to 0.0 (95% CI 0.00-0.15) in patients negative for both. CONCLUSIONS: PDX-1mRNA is detectable in samples of pancreatic cancer. Its quantification may be helpful to improve the diagnosis of pancreatic cancer.
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Carcinoma Ductal Pancreático/genética , Cistadenocarcinoma Mucinoso/genética , Cistadenocarcinoma Seroso/genética , Proteínas de Homeodomínio/genética , Neoplasias Pancreáticas/genética , RNA Mensageiro/metabolismo , Transativadores/genética , Idoso , Carcinoma Ductal Pancreático/diagnóstico , Estudos de Casos e Controles , Cistadenocarcinoma Mucinoso/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Pseudocisto Pancreático/diagnóstico , Pancreatite Crônica/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Feminino , Histocitoquímica , Humanos , Imuno-Histoquímica , Microscopia , Pessoa de Meia-Idade , Neurilemoma/patologia , Neoplasias Pancreáticas/patologia , Radiografia Abdominal , Proteínas S100/análise , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Gastric carcinoma is one of the most common malignancies in the world. Skeletal muscle metastases from gastric carcinoma are rare. CASE REPORT: We report a case of a 67-year-old man patient with skeletal muscle metastasis developing from gastric carcinoma. He had a painful swelling of the left thigh. A chest computed tomography (CT) scan with enhancement showed pulmonary thromboembolism. Despite heparin therapy, edema and pain of the lower limbs increased bilaterally, so the patient underwent pelvic magnetic resonance imaging (MRI), which documented an altered signal intensity in the upper third of his thighs bilaterally. Furthermore, the examination of the ultrasound (US)-guided biopsy specimen of the left gluteal muscle showed signet ring cell adenocarcinoma metastasis. An upper gastrointestinal tract endoscopy confirmed a gastric ulceration, with a biopsy positive for signet ring cell adenocarcinoma. Because of the advanced stage of disease, the patient underwent only supportive care and died 74 days after admission. CONCLUSIONS: Skeletal muscle metastasis may be the initial presentation of gastric carcinoma and diagnosis could be difficult. Biopsy is mandatory for diagnosis.
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Carcinoma de Células em Anel de Sinete/secundário , Neoplasias Musculares/secundário , Músculo Esquelético , Neoplasias Gástricas/patologia , Idoso , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/terapia , Evolução Fatal , Humanos , Masculino , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/terapia , Coxa da PernaRESUMO
The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features.