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1.
Clin Epigenetics ; 11(1): 152, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666119

RESUMO

BACKGROUND: Men often undergo repeat prostate biopsies because of suspicion of missed cancer. We assessed if (i) methylation of selected genes in prostate tissue vary with aging and (ii) methylation alterations in repeat biopsies predict missed prostate cancer. METHODS: We conducted a case-control study among men who underwent at least two negative prostate biopsies followed by a sampling either positive (cases n = 111) or negative (controls n = 129) for prostate cancer between 1995 and 2014 at the University Hospital (Turin, Italy). Two pathology wards were included for replication purposes. We analyzed methylation of GSTP1, APC, PITX2, C1orf114, GABRE, and LINE-1 in the first two negative biopsies. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between genes methylation and prostate cancer. RESULTS: Age at biopsy and time interval between the two negative biopsies were not associated with methylation levels of the selected genes in neither cases nor controls. GSTP1 methylation in the first and in the second negative biopsy was associated with prostate cancer detection [OR per 1% increase: 1.14 (95% CI 1.01-1.29) for the second biopsy and 1.21 (95% CI 1.07-1.37) for the highest methylation level (first or second biopsy)]. A threshold > 10% for GSTP1 methylation corresponded to a specificity of 0.98 (positive likelihood ratio 7.87). No clear association was found for the other genes. Results were consistent between wards. CONCLUSIONS: Our results suggest that GSTP1 methylation in negative prostate biopsies is stable over time and can predict missed cancer with high specificity.

2.
Lung Cancer ; 138: 27-34, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606522

RESUMO

OBJECTIVES: Thymomas are rare neoplasms with a low recurrence rate, which are preferably surgically treated. Iterative thymoma surgery has not been well investigated yet. Study aim is to analyse prognostic factors after iterative recurrence treatment. METHODS: Clinical, pathological and surgical findings of 155 patients, treated for thymoma recurrence in three high-volume centres from 01/01/1990 to 1/07/2017, were retrospectively reviewed. Recurrence patterns/treatment types (surgery or chemotherapy, radiotherapy or combined) were correlated to overall (OS) and disease free survival (DFS). RESULTS: Myasthenia Gravis was present in 135 (87%) patients. Surgery was performed in 135/155 (87%) patients with 109 (80.7%) complete resections. Sixty (55%)patients experienced a second recurrence surgically treated in 31/60 (52%) cases with 18 (58%) complete resections. Eleven (61%) patients experienced a third recurrence and nine underwent complete resection. Myastenia Gravis (HR: 0.45; 95% CI: 0.20-0.98, p = 0.046), DFS after the initial thymectomy >36 months (HR: 0.9; 95% CI: 0.96-0.99, p = 0.006) and complete second recurrence resection (HR: 1.45; 95% CI 2.07-10.01, p = 0.010) resulted as independent favorable prognostic survival factor. Despite patient selection bias, rewarding long-term survivals was predictable after iterative thymoma surgery (5 and 10 years survival of 79.6% and 64.6%) while a poor prognosis was observed after CT/RT (5 and 10 years OS of 56.7% and 21.5%), Masaoka stage and DFS > 36 months were risk factor for iterative recurrences. CONCLUSIONS: Myasthenia Gravis and long DFS after thymectomy are favorable survival factors for multiple thymoma recurrences. Iterative surgical treatment is a viable therapeutic option associated to long-term survival if technically and clinically feasible.

3.
Am J Epidemiol ; 188(6): 1165-1173, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30976789

RESUMO

In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced.

4.
Abdom Radiol (NY) ; 44(5): 1883-1893, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30788558

RESUMO

PURPOSE: To study the detection of clinically significant prostate cancer (PCa) by readers with different experience, comparing performance with biparametric magnetic resonance imaging (bmMRI) and with the reference multiparametric (mpMRI). METHODS: Retrospective analysis of 68 patients with mpMRI of the prostate at 1.5 Tesla using a 32 phased-array coil. Forty-five patients (cases) underwent radical prostatectomy, whereas 23 (controls) had a negative prostate biopsy and ≥ 2.5 years of negative follow-up. Six observers (two with 1000 cases interpreted, two with 300, two with 100) performed the analysis first with bpMRI including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps and T2-weighted (T2W) imaging in three planes and, after 1 month, with mpMRI, adding dynamic contrast enhancement (DCE). The performance was quantified by sensitivity (SNS), specificity (SPC) and area under the curve (AUC) of the ROC (Receiver Operating Characteristics) procedure. RESULTS: Concordance within observers of equivalent experience was good (weighted Cohen's k ≈ 0.7). The two expert readers performed as well in bpMRI as in mpMRI (SNS = 0.91-0.96, AUC = 0.86-0.93; p ≥ 0.10); readers with 300 cases performed well in mpMRI, but significantly worse in bpMR: SNS = 0.58 versus 0.91 (p < 0.0001) and AUC = 0.73 versus 0.86 (p = 0.01); the limited experience of readers with 100 cases showed in mpMRI (SNS = 0.71; AUC = 0.77) and even more in bpMRI (SNS = 0.50; AUC = 0.68). CONCLUSION: The study revealed the impact of the readers' experience when using bpMRI. The bpMRI without contrast media was a valid alternative for expert readers, whereas less experienced ones needed DCE to significantly boost SNS and AUC. Results indicate 700-800 cases as threshold for reliable interpretation with bpMRI.

5.
Int J Lab Hematol ; 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30480372

RESUMO

INTRODUCTION: Nonhemopoietic neoplasms (NHNs) may be encountered during routine flow cytometry (FC) immunophenotyping. The clue of their presence mainly relies on detection of CD45-negative (CD45-) cells with altered scatter parameters. METHODS: In this study, we evaluated a monoclonal antibody combination conceived to characterize the CD45- population by FC, suspected of belonging to NHNs, when present. The panel included CD45 for leucocytes identification, CD326 (clones BerEP4 and HEA-125) to mark epithelial cells, CD33 to identify myeloid cells, CD138 to trace plasma cells and CD56 useful in the identification of neuroendocrine tumours. 7AAD vital dye was used to gate out dead cells. Results were correlated with cytomorphology and confirmed by histological data, if available. RESULTS: Among 9422 specimens submitted for routine FC investigation, 47 samples that included fine-needle aspirates, bone marrow aspirates, tissue biopsies and body fluids had a detectable CD45- population and a sufficient cell amount to be further investigated. FC revealed the presence of CD326-positive epithelial cells in 38 specimens; altered scatter parameters and variable reactivity to the other antigens tested allowed to suspect NHNs in the remaining nine samples. The presence of NHNs was confirmed in all cases by morphology. CONCLUSIONS: The current results show that when CD45- cells with altered scatter parameters were detected, cytometrists involved in leukaemia/lymphoma diagnosis may require further FC investigations to rapidly identify NHNs in different specimens, thus reducing the time of the immunohistochemical diagnostic workup to reach a final diagnosis.

6.
BMC Cancer ; 18(1): 439, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29669525

RESUMO

BACKGROUND: Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs. METHODS: OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves. RESULTS: A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC. CONCLUSIONS: In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.

7.
Exp Clin Transplant ; 16(2): 172-176, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29108514

RESUMO

OBJECTIVES: Due to widespread exploitation of extended criteria donors, machine perfusion is emerging as an alternative to static cold storage for organ preservation. Hypothermic oxygenated machine perfusion has been associated with improved outcomes after liver transplant, both in laboratory and clinical settings. Here, we present our initial experience with hypothermic oxygenated machine perfusion, evaluating incidence of postreperfusion syndrome, early allograft dysfunction, and long-term biliary complications. MATERIALS AND METHODS: End-ischemic dual (hepatic artery and portal vein) hypothermic oxygenated machine perfusion was carried out for 150 to 200 minutes before organ implantation in 4 liver transplants considered at increased risk due to donor, recipient, or matching issues. RESULTS: No device malfunction occurred. Theatre logistics were minimally affected. Incidences of post-reperfusion syndrome and early allograft dysfunction were 25% and 50%. At 6-month follow-up, all patients were alive with normal hepatic function and no evidence of ischemic cholangiopathy. CONCLUSIONS: In our experience, hypothermic oxygenated machine perfusion appeared safe and logistically simple. Further studies are needed to assess the real value of this technique and to identify which subset of patients would benefit from its implementation.


Assuntos
Temperatura Baixa , Hipotermia Induzida/métodos , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Oxigênio , Perfusão/métodos , Adulto , Doenças Biliares/diagnóstico , Doenças Biliares/etiologia , Biópsia , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/instrumentação , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Preservação de Órgãos/efeitos adversos , Preservação de Órgãos/instrumentação , Perfusão/efeitos adversos , Perfusão/instrumentação , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/etiologia , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Epigenetics ; 12(1): 11-18, 2017 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-27892790

RESUMO

Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.


Assuntos
Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos/genética , Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos de Associação Genética , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Próstata/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Análise de Sobrevida
9.
Radiol Med ; 121(11): 873-881, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27447803

RESUMO

OBJECTIVE: Stereotactic ablative radiotherapy (SABR) is a safe treatment approach for hepatocellular carcinoma (HCC) with comparable effectiveness to other local therapies. Only scant information is available concerning the role of SABR prior to liver transplantation (LT) for HCC. We present a consecutive case series investigating the role of SABR as a bridge or downstaging option in HCC patients subsequently submitted to LT. MATERIALS AND METHODS: Between September 2012 and May 2014, 8 patients for a total of 13 lesions underwent SABR prior to LT. Inclusion criteria were a pathological or radiological diagnosis of HCC, lesion size ≤6 cm or lesion number ≤3 with a total diameter ≤6 cm, no extrahepatic metastases, Child-Pugh class A-B, ECOG performance status ≤1. Patients were prescribed 36-48 Gy in 3-5 fractions (8 Gy × 5 fractions or 16 Gy × 3 fractions), in 3-5 consecutive days according to clinical and dosimetric decision making. Radiological response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Pathological response was assessed through the rate of tumor necrosis relative to the total tumor volume. Acute and late toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 (CTCAE v 4.0). RESULTS: Among the 13 pathologically evaluated lesions, 8 (61.5 %) lesions had a complete response 2 (15.3 %) had a minimal pathological response and other 2 (15.3 %) showed stable disease. The remaining lesion had a significant pathological response. Maximum detected toxicity included a G2 GGT increase in two patients (at 1 and 3 months respectively). One patient developed a non-classic RILD with a fivefold increase in transaminase enzymes level and a shift in Child-Pugh category from B7 to C10 due to bilirubin increase. Only one modification in the surgical strategy was needed during LT. CONCLUSIONS: SABR proved to be a safe and effective local therapy prior to LT in HCC patients. Prospective controlled clinical trials are needed to evaluate its efficacy compared to other local therapies in this setting.


Assuntos
Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Técnicas Estereotáxicas , Resultado do Tratamento , Carga Tumoral
10.
Hum Pathol ; 56: 81-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27342909

RESUMO

Androgen deprivation therapy (ADT) is the standard of care for metastatic prostate cancer and initially induces tumor regression, but invariably results in castration-resistant prostate cancer through various mechanisms, incompletely discovered. Our aim was to analyze the dynamic modulation, determined by ADT, of the expression of selected genes involved in the pathogenesis and progression of prostate cancer (TMPRSS2:ERG, WNT11, SPINK1, CHGA, AR, and SPDEF) using real-time polymerase chain reaction in a series of 59 surgical samples of prostate carcinomas, including 37 cases preoperatively treated with ADT and 22 untreated cases, and in 43 corresponding biopsies. The same genes were analyzed in androgen-deprived and control LNCaP cells. Three genes were significantly up-modulated (WNT11 and AR) or down-modulated (SPDEF) in patients treated with ADT versus untreated cases, as well as in androgen-deprived LNCaP cells. The effect of ADT on CHGA gene up-modulation was almost exclusively detected in cases positive for the TMPRSS2:ERG fusion. The correlation between biopsy and surgical samples was poor for most of the tested genes. Gene expression analysis of separate tumor areas from the same patient showed an extremely heterogeneous profile in the 6 tested cases (all untreated). In conclusion, our results strengthened the implication of ADT in promoting a prostate cancer aggressive phenotype and identified potential biomarkers, with special reference to the TMPRSS2:ERG fusion, which might favor the development of neuroendocrine differentiation in hormone-treated patients. However, intratumoral heterogeneity limits the use of gene expression analysis as a potential prognostic or predictive biomarker in patients treated with ADT.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Terapia Neoadjuvante , Neoplasias da Próstata/tratamento farmacológico , Transcriptoma/efeitos dos fármacos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Biópsia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Resultado do Tratamento
11.
Virchows Arch ; 468(2): 159-67, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26563401

RESUMO

Confirmation of endoscopically suspected esophageal metaplasia (ESEM) requires histology, but confusion in the histological definition of columnar-lined esophagus (CLE) is a longstanding problem. The aim of this study is to evaluate interpathologist variability in the interpretation of CLE. Thirty pathologists were invited to review three ten-case sets of CLE biopsies. In the first set, the cases were provided with descriptive endoscopy only; in the second and the third sets, ESEM extent using Prague criteria was provided. Moreover, participants were required to refer to a diagnostic chart for evaluation of the third set. Agreement was statistically assessed using Randolph's free-marginal multirater kappa. While substantial agreement in recognizing columnar epithelium (K = 0.76) was recorded, the overall concordance in clinico-pathological diagnosis was low (K = 0.38). The overall concordance rate improved from the first (K = 0.27) to the second (K = 0.40) and third step (K = 0.46). Agreement was substantial when diagnosing Barrett's esophagus (BE) with intestinal metaplasia or inlet patch (K = 0.65 and K = 0.89), respectively, in the third step, while major problems in interpretation of CLE were observed when only cardia/cardia-oxyntic atrophic-type epithelium was present (K = 0.05-0.29). In conclusion, precise endoscopic description and the use of a diagnostic chart increased consistency in CLE interpretation of esophageal biopsies. Agreement was substantial for some diagnostic categories (BE with intestinal metaplasia and inlet patch) with a well-defined clinical profile. Interpretation of cases with cardia/cardia-oxyntic atrophic-type epithelium, with or without ESEM, was least consistent, which reflects lack of clarity of definition and results in variable management of this entity.


Assuntos
Esôfago de Barrett/patologia , Epitélio/patologia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Adulto , Idoso , Esôfago de Barrett/diagnóstico , Biópsia , Neoplasias Esofágicas/diagnóstico , Humanos , Metaplasia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
12.
Endosc Int Open ; 3(2): E165-70, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26135662

RESUMO

BACKGROUND AND STUDY AIMS: The HER2 status of small endoscopic biopsies is important for predicting the eligibility of patients with metastatic HER2-positive gastric cancer or gastro-esophageal junction (GEJ) cancer for anti-HER2 therapy approved by the U.S. Food and Drug Administration. The aim of this study was to identify the minimum biopsy set required to evaluate the HER2 status with confidence. PATIENTS AND METHODS: A total of 103 consecutive patients with resected gastric cancer or GEJ cancer were retrospectively selected; 2 formalin-fixed, paraffin-embedded samples of each surgical specimen and all paired endoscopic biopsies were analyzed for HER2 status with both immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) methods. A total of 10 virtual biopsies were constructed by selecting areas 2.6 mm in diameter on the luminal side of digitalized slides obtained from the surgical specimens. The results of evaluating HER2 status in virtual biopsies, slides containing complete surgical specimens, and endoscopic biopsies were compared. The resulting minimum biopsy set was applied to the endoscopic biopsy series for validation. RESULTS: A biopsy set containing a minimum of 5 samples was identified as the most accurate in predicting HER2 status (sensitivity, 92 %; specificity, 97 %). In only 3 of the 103 cases (2.9 %) did a comparison of the HER2 evaluation of virtual biopsies and that of entire slides show inconsistent results. Overall agreement between the endoscopic biopsies and surgical samples for HER2 IHC status increased from 78.4 % to 92.3 % when biopsy sets containing 4 or fewer samples were compared with biopsy sets containing 5 or more samples. CONCLUSIONS: Although the recommendations suggest that 8 to 10 biopsies are necessary, the results show that a minimum set of 5 biopsies may be sufficient for reliable HER2 assessment in gastric cancer and GEJ cancer. However, endoscopists should be aware that a smaller sample size may be less accurate in selecting patients eligible for anti-HER2 therapy.

13.
PLoS One ; 10(4): e0121815, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25844806

RESUMO

The selection of proper tissues from formalin-fixed and paraffin-embedded tumors before diagnostic molecular testing is responsibility of the pathologist and represents a crucial step to produce reliable test results. The international guidelines suggest two cut-offs, one for the percentage and one for the number of tumor cells, in order to enrich the tumor content before DNA extraction. The aim of the present work was two-fold: to evaluate to what extent a low percentage or absolute number of tumor cells can be qualified for somatic mutation testing; and to determine how assay sensitivities can guide pathologists towards a better definition of morphology-based adequacy cut-offs. We tested 1797 tumor specimens from melanomas, colorectal and lung adenocarcinomas. Respectively, their BRAF, K-RAS and EGFR genes were analyzed at specific exons by mutation-enriched PCR, pyrosequencing, direct sequencing and real-time PCR methods. We demonstrate that poorly cellular specimens do not modify the frequency distribution of either mutated or wild-type DNA samples nor that of specific mutations. This observation suggests that currently recommended cut-offs for adequacy of specimens to be processed for molecular assays seem to be too much stringent in a laboratory context that performs highly sensitive routine analytical methods. In conclusion, new cut-offs are needed based on test sensitivities and documented tumor heterogeneity.


Assuntos
Neoplasias Colorretais/patologia , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/patologia , Melanoma/patologia , Inclusão em Parafina/normas , Neoplasias Colorretais/genética , Receptores ErbB/genética , Fixadores/química , Formaldeído/química , Humanos , Neoplasias Pulmonares/genética , Melanoma/genética , Inclusão em Parafina/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética
14.
Case Rep Surg ; 2015: 256838, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26783488

RESUMO

Endometrial carcinoma is the most common neoplasia of female genital tract. The prognosis of early stage disease (FIGO I and FIGO II) is excellent: recurrence after surgery is less than 15%, most of which are reported within 3 years after primary treatment. Herein we report a case of late rectal recurrence from FIGO Ib endometrial adenocarcinoma. Patient had also familiar and personal history of colonic adenocarcinoma and previous findings of microsatellite instability (MSI); molecular analysis evidenced heterozygotic somatic mutation in MLH1 gene. Twenty-eight years after hysterectomy and bilateral salpingoovariectomy, a rectal wall mass was detected during routine colonoscopy. Patients underwent CT scan, pelvic MRI, and rectal EUS with FNA: histopathological and immunohistochemical analysis revealed differentiated carcinoma cells of endometrial origin. No neoadjuvant treatment was planned and low rectal anterior resection with protective colostomy was performed; histology confirmed rectal lesion as metastasis from endometrial carcinoma. Recurrence of early stage endometrial carcinoma after a long period from primary surgery is possible. It is important to keep in mind this possibility in order to set a correct diagnostic and therapeutic algorithm, including preoperative immunohistochemical staining, and to plan a prolonged follow-up program.

15.
JOP ; 15(5): 512-4, 2014 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-25262724

RESUMO

CONTEXT: Primary venous leiomyosarcoma (LMS) is a rare disease, most commonly affecting the retroperitoneal veins and in particular the inferior vena cava. Five-year survival rate ranges between 33% and 68%. CASE REPORT: Complete surgical resection represents the only potentially curative treatment, occasionally achieving long-term survival. LMS of the splenic vein is extremely rare, with only three cases reported in the literature. CONCLUSION: We report a case of primary venous LMS arising from the splenic vein and we briefly review the relevant literature.

16.
J Craniofac Surg ; 25(2): e149-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24621755

RESUMO

Localized nasal argyria has been reported in 3 published articles as secondary to occupational exposure and involving the anterior part of the nose. No previous cases of such pathology involving the rhinopharynx were described. Here we report the first case of localized argyria of the roof and of the posterior wall of the rhinopharynx secondary to prolonged use of nasal drops containing colloidal silver protein. The recognition of such pathology can be useful to increase the number of conditions that must be considered in the differential diagnosis of rhinopharyngeal mucosa alterations.


Assuntos
Argiria/diagnóstico , Argiria/etiologia , Hidrogéis/administração & dosagem , Hidrogéis/efeitos adversos , Doenças Nasofaríngeas/induzido quimicamente , Doenças Nasofaríngeas/diagnóstico , Compostos de Prata/administração & dosagem , Compostos de Prata/efeitos adversos , Administração Intranasal/efeitos adversos , Argiria/patologia , Feminino , Humanos , Hipertrofia/patologia , Doença Iatrogênica , Pessoa de Meia-Idade , Nasofaringe/patologia
17.
J Mol Diagn ; 16(2): 190-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24378251

RESUMO

MammaPrint, a prognostic 70-gene profile for early-stage breast cancer, has been available for fresh tissue. Improvements in RNA processing have enabled microarray diagnostics for formalin-fixed, paraffin-embedded (FFPE) tissue. Here, we describe method optimization, validation, and performance of MammaPrint using analyte from FFPE tissue. Laboratory procedures for enabling the assay to be run on FFPE tissue were determined using 157 samples, and the assay was established using 125 matched FFPE and fresh tissues. Validation of MammaPrint-FFPE, compared with MammaPrint-fresh, was performed on an independent series of matched tissue from five hospitals (n = 211). Reproducibility, repeatability, and precision of the FFPE assay (n = 87) was established for duplicate analysis of the same tumor, interlaboratory performance, 20-day repeat experiments, and repeated analyses over 12 months. FFPE sample processing had a success rate of 97%. The MammaPrint assay using FFPE analyte demonstrated an overall equivalence of 91.5% (95% confidence interval, 86.9% to 94.5%) between the 211 independent matched FFPE and fresh tumor samples. Precision was 97.3%, and repeatability was 97.8%, with highly reproducible results between replicate samples of the same tumor and between two laboratories (concordance, 96%). Thus, with 580 tumor samples, MammaPrint was successfully translated to FFPE tissue. The assay has high precision and reproducibility, and FFPE results are substantially equivalent to results derived from fresh tissue.


Assuntos
Detecção Precoce de Câncer/métodos , Perfilação da Expressão Gênica/métodos , Detecção Precoce de Câncer/normas , Formaldeído , Perfilação da Expressão Gênica/normas , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Inclusão em Parafina , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fixação de Tecidos
18.
Mod Pathol ; 27(9): 1246-54, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24434900

RESUMO

Mitotic count on hematoxylin and eosin slides is a fundamental morphological criterion in the diagnosis and grading of adrenocortical carcinoma in any scoring system employed. Moreover, it is the unique term strongly associated with patient's prognosis. Phospho-histone H3 is a mitosis-specific antibody, which was already proven to facilitate mitotic count in melanoma and other tumors. Therefore, a study was designed to assess the diagnostic and prognostic role of phospho-histone H3 in 52 adrenocortical carcinomas, comparing manual and computerized count to standard manual hematoxylin- and eosin-based method and Ki-67 index. Manual hematoxylin and eosin and phospho-histone H3 mitotic counts were highly correlated (r=0.9077, P<0.0001), better than computer-assisted phospho-histone H3 evaluations, and had an excellent inter-observer reproducibility at Bland-Altman analysis. Three of 15 cases having <5 mitotic figures per 50 high-power fields by standard count on hematoxylin and eosin gained the mitotic figure point of Weiss Score after a manual count on phospho-histone H3 slides. Traditional mitotic count confirmed to be a strong predictor of overall survival (P=0.0043), better than phospho-histone H3-based evaluation (P=0.051), but not as strong as the Ki-67 index (P<0.0001). The latter further segregated adrenocortical carcinomas into three prognostic groups, stratifying cases by low (<20%), intermediate (20-50%), and high (>50%) Ki-67 values. We conclude that (a) phospho-histone H3 staining is a useful diagnostic complementary tool to standard hematoxylin and eosin mitotic count, enabling optimal mitotic figure evaluation (including atypical mitotic figures) even in adrenocortical carcinomas with a low mitotic index and with a very high reproducibility; (b) Ki-67 proved to be the best prognostic indicator of overall survival, being superior to the mitotic index, irrespective of the method (standard on hematoxylin and eosin or phospho-histone H3-based) used to count mitotic figures.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Histonas/metabolismo , Antígeno Ki-67/metabolismo , Índice Mitótico , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/patologia , Adulto , Idoso , Amarelo de Eosina-(YS) , Feminino , Hematoxilina , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosforilação , Prognóstico , Taxa de Sobrevida , Adulto Jovem
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