Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
PLoS One ; 12(8): e0182073, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28806416

RESUMO

BACKGROUND: The role of nipple discharge cytology (NDc) in the surgical management of breast cancer patients is unclear. We aimed: (i) to evaluate the effect of malignant NDc on the surgical approach to the nipple-areola complex, and (ii) to verify the association between malignant NDc and nipple malignancy. METHODS: We retrospectively analyzed a case series of 139 patients with NDc who underwent breast surgery. The clinical and histological findings, types of surgery with emphasis on nipple-areola complex amputation, immunohistochemical phenotypes of the carcinomas and measurements of the tumor-nipple distance were recorded. Additionally, in patients who showed HER2-positive lesions on definitive surgery, we evaluated the HER2 immunocytochemistry of the NDc smears. RESULTS: Thirty-two malignant and 107 benign/borderline NDc diagnoses were identified. All 32 malignant-NDc cases were histologically confirmed as malignant. Thirty borderline/benign-NDc cases were histologically diagnosed as malignant (sensitivity 58%). The majority of the patients with malignant NDc were treated with nipple-areola complex amputations in both the mastectomy and conservative surgery groups (P<0.001, χ251.77). Nipple involvement was strongly associated with HER2-positive ductal carcinoma in-situ (P<0.001, χ211.98). HER2 immunocytochemistry on the NDc revealed a 100% correlation with the immunocytochemistry performed on the surgical tissues. CONCLUSIONS: Malignant NDc influenced surgical management. The association of malignant NDc with nipple involvement is highly related to ductal carcinoma in-situ with HER2 overexpression. In case of HER2 positive NDc, nipple-areola complex involvement is more likely than in HER2 negative cases.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Derrame Papilar/citologia , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mamilos/patologia , Mamilos/cirurgia , Receptor ErbB-2/metabolismo , Coloração e Rotulagem
2.
Cancer Cytopathol ; 125(3): 212-220, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27926800

RESUMO

BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16ink4a ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists. RESULTS: The overall κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358-0.642] and κ = 0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384-0.866]; second evaluation, κ = 0.403 [95% CI, 0.182-0.643]). CONCLUSIONS: Dual staining for p16 ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. © 2016 American Cancer Society.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/análise , Antígeno Ki-67/análise , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Feminino , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes
3.
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
4.
Cancer Cytopathol ; 123(4): 212-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25534957

RESUMO

BACKGROUND: The triage of human papillomavirus (HPV)-positive women is needed to avoid overreferral to colposcopy. p16(INK4a) immunostaining is an efficient triage method. p16(INK4a) /Ki-67 dual staining was introduced mainly to increase reproducibility and specificity compared with stand-alone p16(INK4a) staining. METHODS: Within a pilot project, HPV-positive women were referred to colposcopy if cytology was abnormal or unsatisfactory or HPV testing was still positive after 1 year. For 500 consecutive women, a slide obtained during colposcopy was immunostained for p16(INK4a) /Ki-67 and independently interpreted by 7 readers without previous experience with dual staining. Four of these readers were experts in cervical pathology and 3 were not. Kappa values for multiple raters, sensitivity, and specificity for cervical intraepithelial neoplasia type 2-positive histology were computed. Because women with normal cytology were underrepresented, estimates for all HPV-positive women were obtained as weighted means of cytology-specific estimates. RESULTS: The overall kappa for HPV-positive women was 0.70 (95% confidence interval [95% CI], 0.60-0.77). Kappa values were not found to be significantly different between expert and nonexpert readers with regard to cervical cytology but were significantly increased (P =. 0066) after consensus discussion. The overall specificity estimate for HPV-positive women was 64.0% (95% CI, 57.4%-70.2%): 66.7% (95% CI, 59.8%-73.0%) for experts and 60.5% (95% CI, 59.8%-73.0%) for nonexperts. Among women with abnormal cytology, the sensitivity was 85.5% (95% CI, 77.9%-90.8%): 85.8% (95% CI, 77.9%-91.2%) for experts and 85.1% (95% CI, 76.6%-90.9%) for nonexperts. CONCLUSIONS: p16(INK4a) /Ki-67 immunostaining demonstrated good reproducibility and specificity when triaging HPV-positive women. Dual-staining interpretation can be performed, after short training, even by staff who are not experts in cervical cytology. This allows HPV-based screening with triage to be performed in settings in which such expert staff is not available.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Antígeno Ki-67/metabolismo , Infecções por Papillomavirus/diagnóstico , Triagem/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colo do Útero/metabolismo , Colo do Útero/patologia , Citodiagnóstico , Detecção Precoce de Câncer , Prova Pericial , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Oncologist ; 19(11): 1118-26, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25323485

RESUMO

BACKGROUND: The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess the impact of distinct recommendations with regard to identifying patients eligible for anti-HER2 agents by fluorescence in situ hybridization (FISH) and to elucidate whether multiplex ligation-dependent probe amplification (MLPA) may be of support in assessing HER2 gene status. METHODS: A cohort of 957 immunohistochemistry-evaluated HER2-equivocal cases was analyzed by dual-color FISH. The results were assessed according to U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) 2007 and 2013 guidelines for dual- and single-signal in situ hybridization (ISH) assays. A subgroup of 112 cases was subjected to MLPA. RESULTS: HER2 amplification varied from 15% (ASCO/CAP 2007 HER2/CEP17 ratio) to 29.5% (FDA/EMA HER2 copy number). According to the ASCO/CAP 2013 interpretation of the dual-signal HER2 assay, ISH-positive carcinomas accounted for 19.7%. In contrast with the ASCO/CAP 2007 ratio, this approach labeled as positive all 32 cases (3.34%) with a HER2/CEP17 ratio <2 and an average HER2 copy number ≥6.0 signals per cell. In contrast, only one case showing a HER2 copy number <4 but a ratio ≥2 was diagnosed as positive. MLPA data correlated poorly with FISH results because of the presence of heterogeneous HER2 amplification in 33.9% of all amplified carcinomas; however, MLPA ruled out HER2 amplification in 75% of ISH-evaluated HER2-equivocal carcinomas. CONCLUSION: The ASCO/CAP 2013 guidelines seem to improve the identification of HER2-positive carcinomas. Polymerase chain reaction-based methods such as MLPA can be of help, provided that heterogeneous amplification has been ruled out by ISH.


Assuntos
Neoplasias da Mama/genética , Reação em Cadeia da Polimerase/métodos , Receptor ErbB-2/genética , Autoantígenos/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Estudos de Coortes , Feminino , Amplificação de Genes , Dosagem de Genes , Guias como Assunto , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Receptor ErbB-2/metabolismo
6.
PLoS One ; 9(9): e106640, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25207643

RESUMO

BACKGROUND: Recent studies have demonstrated that axillary lymph node dissection (ALND) does not affect patient survival, even in those with one or two positive sentinel lymph nodes (SLNs). On the other hand, patients with 3 or more metastatic lymph nodes are eligible for chemotherapy. Therefore, it is crucial to identify a priori patients at risk of having a high number of metastatic axillary lymph nodes for their surgical and/or clinical management. Ultrasound (US) guided Fine-Needle Aspiration (FNA) has been proven to be a useful and highly specific method for detecting metastatic axillary lymph nodes. However, only one recent study has evaluated the efficiency of this method in identifying patients with high metastatic nodal involvement. Our aim was to validate US-guided FNA as a reliable method to discriminate a priori patients with >3 metastatic lymph nodes. METHODS: A retrospective series of 1287 breast cancer patients who underwent a simultaneous preoperative breast and axillary US to stage their axilla was collected. A total of 365 patients, with either positive SLNs (278) or positive axillary lymph nodes detected via US-guided FNA (87), underwent ALND. In these two subgroups, we compared the number of metastatic lymph nodes in the axilla. RESULTS: The number of metastatic axillary lymph nodes in patients who underwent US-guided FNA was significantly higher (63% had >3 metastatic lymph nodes) than that in patients with SLNs positive for micro- or macrometastases (3% and 27%, respectively) (P<0.001, χ(2) = 117.897). CONCLUSIONS: Preoperative axillary US-guided FNA could act as a reliable tool in identifying breast cancer patients with extensive nodal involvement.


Assuntos
Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Período Pré-Operatório , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Axila , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Biópsia de Linfonodo Sentinela , Ultrassonografia
7.
Transl Oncol ; 5(3): 180-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22741037

RESUMO

We investigated whether residual material from diagnostic smears of fine needle aspirations (FNAs) of mammographically detected breast lesions can be successfully used to extract RNA for reliable gene expression analysis. Twenty-eight patients underwent FNA of breast lesions under ultrasonographic guidance. After smearing slides for cytology, residual cells were rinsed with TRIzol to recover RNA. RNA yield ranged from 0.78 to 88.40 µg per sample. FNA leftovers from 23 nonpalpable breast cancers were selected for gene expression profiling using oligonucleotide microarrays. Clusters generated by global expression profiles partitioned samples in well-distinguished subgroups that overlapped with clusters obtained using "biologic scores" (cytohistologic variables) and differed from clusters based on "technical scores" (RNA/complementary RNA/microarray quality). Microarray profiling used to measure the grade of differentiation and estrogen receptor and ERBB2/HER2 status reflected the results obtained by histology and immunohistochemistry. Given that proliferative status in the FNA material is not always assessable, we designed and performed on FNA leftover a multiprobe genomic signature for proliferation genes that strongly correlated with the Ki67 index examined on histologic material. These findings show that cells residual to cytologic smears of FNA are suitable for obtaining high-quality RNA for high-throughput analysis even when taken from small nonpalpable breast lesions.

8.
Ann Surg ; 255(2): 334-42, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21975319

RESUMO

OBJECTIVE: To assess the reliability of using the One-Step Nucleic Acid Amplification (OSNA) assay as a single test on whole sentinel lymph nodes (SLN) as a method of intraoperative diagnosis and staging of SLNs in breast cancer. BACKGROUND: Combining histological and molecular assessment of metastasis on the same SLN may not fully reproduce the actual load of cancer cells present in the SLN and create problems in decisions regarding axillary dissection. METHODS: Selection criteria for the whole SLN OSNA test required that the primary tumor expressed CK19 in more than 80% of tumor cells. Imprint cytology analysis of SLNs was performed together with the OSNA. RESULTS: Of the 279 patients enrolled for SLN evaluation, 123 gave consent to the OSNA protocol and 156 to the standard histology. Thirteen patients were excluded from OSNA evaluation because of low CK19 gene expression in the primary tumor; only 2.3% were truly negative. The kappa of concordance between the imprint cytology and OSNA results was 0.52. The rate of macrometastases determined by OSNA was 11% versus 20% determined by histology, whereas the rate of OSNA-micrometastases (18%) was significantly higher than that determined by histology (8%). The rate of SLN-negative cases was similar between the 2 protocols. Macrometastases correlated with the presence of vascular invasion in both protocols. The rate of axillary lymph node metastases was consistent with SLN tumor load. CONCLUSIONS: Intraoperative OSNA assay performed on the whole SLN gave objective and reproducible results that were useful for directing decisions regarding axillary dissection and for accurately defining the SLN stage.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Queratina-19/genética , Estadiamento de Neoplasias/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Período Intraoperatório , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Micrometástase de Neoplasia/diagnóstico , Reprodutibilidade dos Testes
9.
Trials ; 12: 243, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-22098690

RESUMO

BACKGROUND: In coronary artery bypass grafting surgery, arterial conduits are preferred because of more favourable long-term patency and outcome. Anyway the greater saphenous vein continues to be the most commonly used bypass conduit. Minimally invasive endoscopic saphenous vein harvesting is increasingly being investigated in order to reduce the morbidity associated with conventional open vein harvesting, includes postoperative leg wound complications, pain and patient satisfaction. However, to date the short and the long-term benefits of the endoscopic technique remain controversial. This study provides an interesting opportunity to address this gap in the literature. METHODS/DESIGN: Endoscopic Saphenous harvesting with an Open CO2 System trial includes two parallel vein harvesting arms in coronary artery bypass grafting surgery. It is an interventional, single centre, prospective, randomized, safety/efficacy, cost/effectiveness study, in adult patients with elective planned and first isolated coronary artery disease. A simple size of 100 patients for each arm will be required to achieve 80% statistical power, with a significant level of 0.05, for detecting most of the formulated hypotheses. A six-weeks leg wound complications rate was assumed to be 20% in the conventional arm and less of 4% in the endoscopic arm. Previously quoted studies suggest a first-year vein-graft failure rate of about 20% with an annual occlusion rate of 1% to 2% in the first six years, with practically no difference between the endoscopic and conventional approaches. Similarly, the results on event-free survival rates for the two arms have barely a 2-3% gap. Assuming a 10% drop-out rate and a 5% cross-over rate, the goal is to enrol 230 patients from a single Italian cardiac surgery centre. DISCUSSION: The goal of this prospective randomized trial is to compare and to test improvement in wound healing, quality of life, safety/efficacy, cost-effectiveness, short and long-term outcomes and vein-graft patency after endoscopic open CO2 harvesting system versus conventional vein harvesting.The expected results are of high clinical relevance and will show the safety/efficacy or non-inferiority of one treatment approach in terms of vein harvesting for coronary artery bypass grafting surgery. TRIAL REGISTRATION: www.clinicalTrials.gov NCT01121341.


Assuntos
Protocolos Clínicos , Ponte de Artéria Coronária/métodos , Veia Safena/transplante , Coleta de Tecidos e Órgãos/métodos , Análise Custo-Benefício , Endoscopia , Humanos , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa
10.
Lung Cancer ; 74(1): 25-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21371773

RESUMO

INTRODUCTION: The aim of this study is to evaluate the prognostic factors and outcome of patients operated for adenosquamous (ADS) carcinoma of the lung, in comparison with adenocarcinoma (AD) and squamous cell carcinoma (SCC). METHODS: a retrospective review of our thoracic cancer surgical database for patients operated for ADS, SCC and AD between January, 1995 and December, 2009 was done. RESULTS: Forty-eight patients (39 males, 81.3%) had ADS; complete tumor resection and lymphadenectomy was accomplished in all patients. A higher stage at presentation was observed in ADS, as compared to AD or SCC (p=0.0001). Three and 5-year survival rates were 25% and 15%. ADS overall survival was worse than AD or SCC (p=0.0005). Three and 5-year survival rates of ADS Stage I were similar to those of Stage IIIA AD or SCC. More than half ADS patients developed distant metastases (MTS) or local recurrences. Brain MTS were the most frequent. Median survival for those patients was 8±2.3 months. Postoperative platinum-based chemotherapy statistically improved patients survival (p=0.02). In the multivariate analysis, the presence of MTS (p=0.001), the tumor perineural invasion (p=0.01) and the tumor stage (p=0.0005) were factors associated with poor prognosis. Adjuvant chemotherapy was a significant positive prognostic factor (p=0.00001). CONCLUSIONS: ADS are uncommon and extremely aggressive lung tumors. Adjuvant chemotherapy should be administered even in Stage I radically resected tumors. A whole brain postoperative prophylactic radiotherapy could be proposed to reduce risk of developing brain MTS.


Assuntos
Neoplasias Encefálicas/diagnóstico , Carcinoma Adenoescamoso/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/patologia , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/fisiopatologia , Carcinoma Adenoescamoso/secundário , Carcinoma Adenoescamoso/terapia , Quimioterapia Adjuvante , Progressão da Doença , Feminino , Seguimentos , Humanos , Pulmão/inervação , Pulmão/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
11.
Int J Surg Pathol ; 19(2): 217-9, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18794170

RESUMO

AIM: To describe a case of metastasis of malignant peritoneal epithelioid mesothelioma in gastric antral mucosa in a patient with a cryptogenic liver cirrhosis associated with esophageal varices, abdominal pain and distension, ascites, and weight loss. MATERIALS AND METHOD: The patient underwent esophageal gastric endoscopy for varices, and a biopsy of a polypoid antral lesion was performed. The latter revealed a proliferation of polygonal cells with moderately atypical nuclei and pale eosinophilic, peripherally condensed cytoplasm infiltrating into the lamina propria between the normal mucosal glands of the antrum. The tumor cells were diffusely positive to anticalretinin antibody, whereas anti-claudin 4 and anti-CEA antisera were negative. CONCLUSIONS: Metastases of malignant peritoneal mesotheliomas are unusual, and a predominantly gastrointestinal localization is rare. Pathologists should be aware of this possibility to avoid misdiagnosis, particularly in small biopsy specimens.


Assuntos
Biópsia , Mesotelioma , Humanos , Neoplasias Peritoneais , Peritônio , Estômago
12.
Mod Pathol ; 22(6): 762-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19287465

RESUMO

Columnar cell lesions of the breast are increasingly recognized at mammography for their tendency to calcify. We studied 392 vacuum-assisted core biopsies performed solely for calcifications to evaluate the frequency of columnar cell lesions, their relationship with radiological risk, appearance of calcifications, and clinical data. Management and follow-up of columnar cell lesions without and with atypia (flat epithelial atypia) was analyzed. Cases with architectural atypia (cribriform spaces and/or micropapillae) were excluded from flat epithelial atypia. Calcifications were within the lumen of acini affected by columnar cell lesions in 137 out of 156 biopsies diagnosed with some columnar cell lesions. These represented 37% of vacuum-assisted core biopsies and 62% of low radiological risk (BI-RADS3) calcifications. High-risk (BI-RADS5) calcifications were never associated with columnar cell lesions. Age and menopausal status were comparable in columnar and in not-columnar cell lesions. Atypia was associated with long-term hormone replacement therapy in both lesions. Surgical biopsy was recommended for all cases with atypia. Flat epithelial atypia, as the only histological findings on vacuum-assisted core biopsies, was never associated with malignancy at surgery. In conclusion, we suggest that surgical excision is not mandatory when flat epithelial atypia is found as the most advanced lesion on vacuum-assisted core biopsy performed for low radiological risk calcifications, and that women should be advised of the possible hormone dependency of this entity.


Assuntos
Doenças Mamárias/patologia , Calcinose/patologia , Biópsia , Biópsia por Agulha , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Feminino , Humanos , Mamografia , Lesões Pré-Cancerosas/diagnóstico por imagem , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Fatores de Risco
13.
Ann Thorac Surg ; 87(2): 365-71; discussion 371-2, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19161739

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) are considered important in anticancer immunosurveillance, although their role has not been clearly established yet. We examined prevalence, correlations, and prognostic significance of TIL among our patient population of resected lung neoplasms. METHODS: From 1993 to 2006, the presence of TIL was retrospectively evaluated in 1,290 patients operated on for primary lung neoplasms. Tumor-infiltrating lymphocytes were defined as those intraepithelial lymphocytes located within the cancer cell nests. RESULTS: Tumor-infiltrating lymphocytes were detected in 294 patients (23%). A significant difference was found between prevalence in non-small cell lung carcinomas versus neuroendocrine tumors (290 of 1,208, 24% versus 4 of 82, 5%; p = 0.0001). Prevalence was similar in adenocarcinomas, squamous-cell carcinomas, and large-cell anaplastic carcinomas. Logistic regression analysis indicates that TIL correlate with grading (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55; p = 0.02), tumor dimension (odds ratio, 0.86; 95% confidence interval, 0.79 to 0.94; p = 0.0008), and vascular invasion (odds ratio, 1.62; 95% confidence interval, 1.21 to 2.16; p = 0.0009). A not significantly better survival in the presence of TIL was observed overall (p = 0.20), becoming significant in squamous-cell carcinomas (p = 0.03). In patients with stage I disease, TIL is associated with a significant survival advantage in squamous-cell carcinomas (p = 0.03). The survival advantage increases with the duration of follow-up and is more evident after 4 to 6 years. CONCLUSIONS: Tumor-infiltrating lymphocytes are observed in about one fourth of resected lung neoplasms: they are rare in neuroendocrine tumors. Tumor-infiltrating lymphocytes are more frequent in poorly differentiated tumors and in tumors with microscopic vascular invasion. The presence of TIL correlates with an improved survival in squamous cell carcinomas, particularly at early stage. The survival advantage increases with the duration of follow-up.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Pneumonectomia/métodos , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do Tratamento
14.
J Cell Mol Med ; 13(9B): 4042-50, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18671755

RESUMO

The optimal pathological assessment of sentinel nodes (SLNs) in breast cancer is a matter of debate. Currently, multilevel histological evaluation and immunohistochemistry (IHC) are recommended, but alternative RT-PCR procedures have been developed. To assess the reliability of these different procedures, we devised a step-sectioning protocol at 100 micron-intervals of 74 SLNs using methacarn fixation. mRNA was extracted from sections collected from levels 4 to 5. Mammaglobin, CEA and CK19 were used for RT-PCR. mRNA extraction was successful in 69 SLNs. Of these, 7 showed macrometastases (>2mm), 2 showed micrometastases (<2 mm) and 7 showed isolated tumour cells (ITC) by IHC. RT-PCR was positive for the three markers in 6 of 7 macrometastases and in 1 of 2 micrometastases. In the 2 RT-PCR negative cases, metastases were detected only on sections distant from those analysed by RT-PCR. CEA and/or CK19 were positive by RT-PCR in 3 of 7 ITC and in 23 morphologically negative SLNs. In conclusion, the main goal of our study was to show that the use of alternate sections of the same sample for different procedures is the key reason for the discrepancies between molecular and morphological analyses of SLN. We believe that only prospective studies with quantitative mRNA analysis of specific metastatic markers on the whole lymph node can elucidate the utility of molecular assessments of SLN.


Assuntos
Ácido Acético/química , Neoplasias da Mama/metabolismo , Clorofórmio/química , Imuno-Histoquímica/métodos , Metanol/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Biópsia de Linfonodo Sentinela/métodos , Idoso , Primers do DNA/química , Feminino , Humanos , Oncologia/métodos , Pessoa de Meia-Idade , Metástase Neoplásica
15.
Int J Surg Pathol ; 17(5): 378-83, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18611929

RESUMO

An exponential increase in the detection of papillary thyroid microcarcinomas (PTMCs) has been observed in recent times, possibly because of recent improvements in the management of thyroid lesions and extensive histological examination. However, no definitive treatment guideline has been developed for PTMC, resulting in patients undergoing overtreatment. In 2003, the term papillary microtumor of the thyroid (PMiT) was proposed for small (< or =1 cm) intrathyroidal tumors with excellent prognostic prospects along with strict definition criteria. Since then, the term PMiT has been adopted by clinicians and surgeons. In this article, the authors report a series of 50 consecutive cases of PMiT collected and treated at the University Hospital of Turin, Italy. From the authors' experience, this terminology, which demarks a subset of PTMC, should be widely adopted as it is biologically sound, well accepted by both clinicians and patients, decreases the danger of overtreatment, minimizes the psychological anxiety engendered by a diagnosis of carcinoma, and maintains the patient's eligibility for health insurance.


Assuntos
Adenocarcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Papilar/cirurgia , Adulto , Idoso , Feminino , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Terminologia como Assunto , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Resultado do Tratamento
16.
Lung Cancer ; 64(2): 244-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19041155

RESUMO

We examined the in vitro effects of imatinib (Novartis Pharma AG, Basel, Switzerland) as a possible inhibitor of PDGFR pathway on cells derived from a recurrence of a pleural malignant solitary fibrous tumor (SFT). Primary cell culture was characterised by immunofluorescence. SFT-derived cells were treated with imatinib at different time points. Western blotting for PDGFR-beta, phospho-PDGFR-beta or smooth muscle actin (SMA) was performed before and after 96 h of treatment with imatinib. SFT-derived cells treated with imatinib for 96 h showed a dose dependent decrease of Ki67 expression. Results were confirmed by growth curve. Western blotting showed that PDGFR-beta was highly expressed and phosphorylated in SFT-derived cells and imatinib treatment reduced PDGFR-beta phosphorylation and SMA expression. With the limit of experimental findings, our results support a possible future application of imatinib as a candidate molecule in the target therapy of malignant SFTs over-expressing wild-type PDGFR.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Piperazinas/farmacologia , Pirimidinas/farmacologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/efeitos dos fármacos , Tumor Fibroso Solitário Pleural/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Western Blotting , Células Cultivadas , Cisplatino/administração & dosagem , Feminino , Imunofluorescência , Fluoruracila/administração & dosagem , Humanos , Mesilato de Imatinib , Técnicas In Vitro , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Pneumonectomia , Radioterapia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/biossíntese , Receptor beta de Fator de Crescimento Derivado de Plaquetas/biossíntese , Tumor Fibroso Solitário Pleural/patologia , Tumor Fibroso Solitário Pleural/terapia
17.
Lung Cancer ; 64(1): 117-20, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19046791

RESUMO

Solitary Fibrous Tumours (SFTs) of the pleura are rare neoplasms, with unpredictable biological behaviour. Although usually benign, malignant SFTs are described, and they are often associated with large, necrotic and locally invasive tumours. Radical resection represents the treatment of choice in all cases; recurrences are uncommon, and redo-surgery should be considered. The case of a giant, invasive, radically resected malignant SFT, is described. The role of postoperative radiotherapy, to reduce the risk of recurrence, is also discussed.


Assuntos
Tumor Fibroso Solitário Pleural/patologia , Tumor Fibroso Solitário Pleural/cirurgia , Idoso , Feminino , Humanos , Tumor Fibroso Solitário Pleural/diagnóstico por imagem , Tomografia Computadorizada por Raios X
18.
Lung Cancer ; 61(1): 73-81, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18243402

RESUMO

PURPOSE: To evaluate response rate, toxicity and epidermal growth factor (EGFR) mutations and gene copy number as outcome predictive factors in Italian patients with non-small cell lung cancer (NSCLC) treated with gefitinib (Iressa) in an expanded access program (EAP). PATIENTS AND METHODS: A total of 137 patients with advanced NSCLC received gefitinib as first line treatment or after failure of chemotherapy. In 43 cases, tissue specimens were available for EGFR status evaluation: immunohistochemical (IHC) for EGFR, fluorescence in situ hybridisation (FISH) or Chromogenic in situ hybridisation (CISH)-(ISH) analysis for EGFR and HER2 gene copy number, and PCR-DNA sequencing for mutational analysis of EGFR were performed. RESULTS: In the study population, response rate (PR) was 13%; disease stabilization (DS) 26%; overall disease control rate 39%; median survival 6.3 months and time to progression 2.7 months. Toxicity was mild (G3 skin toxicity in 3% and G3 liver toxicity in 4% of patients). An EGFR-mutation was detected in 9/43 patients: Eight deletions in exon 19 and 1 missense mutation in exon 21. Increased gene copy number for EGFR and/or HER2 was detected in 17/43 patients. Response rate was significantly higher in women, non-smokers, in mutation carriers than in wild type carriers, in EGFR-trisomy/polysomy carriers and HER2-trisomy/polysomy carriers. CONCLUSIONS: In this study, response rate and toxicity to gefitinib treatment were consistent with previously reported data for whites. Female gender, absence of smoking history, EGFR-mutations, EGFR and HER2-polysomy were significantly associated with response to gefitinib therapy in NSCLC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Gefitinibe , Dosagem de Genes , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Prognóstico , Resultado do Tratamento
20.
Mol Cancer Ther ; 6(4): 1223-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17406029

RESUMO

In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutational analysis is an excellent predictor of responsiveness to treatment with tyrosine kinase inhibitors, such as gefitinib. In up to 80% of NSCLCs, cytologic samples or endoscopic biopsies are the only specimens available for molecular analysis, but PCR amplification of DNA from small fixed and paraffin-embedded samples may create artifactual mutations. Fluorescence in situ hybridization (FISH) of EGFR and HER2 has been proposed as an alternative method of analysis. This project aimed to determine the optimal scoring method for FISH or chromogenic in situ hybridization (CISH) assays when analyzing small NSCLC samples to predict response. FISH or CISH analysis of EGFR and HER2 genes was done on 42 small samples derived from NSCLC patients treated with gefitinib. EGFR mutational analysis was done after quantity and quality controls of DNA. In seven of seven cases, a balanced increase in EGFR gene and chromosome 7 number was found to correlate with the presence of specific EGFR mutations. In addition, seven of seven cases with balanced EGFR/HER2 polysomy and two of three cases with balanced EGFR/HER2 trisomy responded to gefitinib (75% of responders). Instead, the EGFR mutations predicted only 7 of 12 (58%) of gefitinib-responsive patients. When only endoscopic biopsies or cytologic specimens are available, we propose using FISH/CISH for EGFR and HER2 as the test of choice for selecting patients for treatment with gefitinib and to consider as negative predictive factor the absence of EGFR/HER2 gene gain.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Hibridização in Situ Fluorescente/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Quinazolinas/uso terapêutico , Receptor ErbB-2/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Sequência de Bases , Biópsia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Análise Mutacional de DNA , Éxons/genética , Feminino , Gefitinibe , Dosagem de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA