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1.
Tumour Biol ; 41(9): 1010428319878536, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31552812

RESUMO

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients' International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama Masculina/metabolismo , Neoplasias da Mama/metabolismo , Histonas/biossíntese , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fosforilação , Receptores Estrogênicos , Receptores de Progesterona
2.
Mol Clin Oncol ; 4(5): 723-727, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27123270

RESUMO

Malignant myoepithelioma of the breast is an extremely rare tumor composed entirely or almost entirely of malignant spindle cells with myoepithelial differentiation. Only a limited number of case reports have been descibed to date; therefore the biological behavior and treatment outcomes of this rare tumor have not been clearly determined. Herein, we present a case of a 74-year-old woman who was admitted with inflammatory-like cancer of the breast, presenting with invasion of the chest wall and axillary lymph node metastasis at the time of diagnosis. The histological examination revealed a tumor composed of epithelioid and spindle cells with moderate to marked nuclear atypia, with foci of hemorrhage and necrosis. The tumor cells were immunoreactive for vimentin, p63, p53, CD10, cytokeratin (CK)8/18, CKAE1-3 and S-100. Finally, a diagnosis of myoepithelial carcinoma of the breast was established. Neoadjuvant chemotherapy was first administered and proved to be ineffective. Due to locoregional progression that was associated with the development of an abscess and subsequent excessive bleeding, a palliative mastectomy was performed. Postoperatively, one more cycle of systemic chemotherapy was administered. However, the patient experienced an early relapse to the chest wall and succumbed to septic shock due to persistent local infection. The aggressiveness and chemoresistance of the tumor in this case was consistent with the existing bibliography.

3.
Ann Ital Chir ; 872016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-28098564

RESUMO

INTRODUCTION: Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. Carcinomas of accessory breast tissue account for ∼0.3% of breast cancers, 5% of which are arising within a supernumerary breast. They are usually diagnosed at a later stage compared with breast cancer, due to their rarity and low clinical suspicion. CASE PRESENTATION: We present the case of a 58 years old male who was admitted to our hospital for an umbilical hernia, surgical repair. During surgery a small skin biopsy was excised and sent for pathological examination as routine procedure. The histological report revealed the presence of a poorly differentiated carcinoma. Immunochemical analysis confirmed adenocarcinoma of breast origin. CONCLUSION: Carcinomas of accessory breast tissue are rare and therefore they are usually of advanced stage in time of diagnosis. Few cases have been reported in literature of accessory breast tissue carcinomas in men. To the best of our knowledge, this is the only case in the literature, of ectopic breast tissue cancer in the umbilicus. KEY WORDS: Ectopic breast, Male breast cancer, Umbilicus.


Assuntos
Neoplasias Abdominais/complicações , Adenocarcinoma/complicações , Neoplasias da Mama Masculina , Mama , Coristoma/complicações , Hérnia Umbilical/complicações , Umbigo/patologia , Neoplasias Abdominais/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Biomarcadores Tumorais , Biópsia , Terapia Combinada , Hérnia Umbilical/cirurgia , Herniorrafia , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica
4.
J BUON ; 20(4): 1164-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26416071

RESUMO

We describe two different cases of prinary thyroid lymphoma (PTL). PTL is a rare malignancy. Nevertheless, it frequently presents diagnostic and therapeutic challenges. The first patient, a 79-year-old female, presented with a large, painless thyroid mass accompanied by severe obstructive symptoms of the upper respiratory and gastrointestinal track. The second patient (67-year-old female) presented with nodular goiter. Thyroidectomy - performed on the first patient for alleviation of obstructive symptoms - revealed the presence of a diffuse large B-cell lymphoma. Although she was administered standard chemotherapy she deceased four months later. In the second patient, primary thyroid lymphoma was an incidental finding following thyroidectomy performed for nodular goiter. These two cases illustrate the variable course of PTL, the possibility of which should be kept into consideration in clinical practice.


Assuntos
Linfoma/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Feminino , Humanos , Linfoma/cirurgia , Estadiamento de Neoplasias , Neoplasias da Glândula Tireoide/cirurgia
5.
J Cancer Res Clin Oncol ; 140(5): 737-48, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24595598

RESUMO

INTRODUCTION: Cetuximab is a monoclonal epidermal growth factor receptor (EGFR)-targeting antibody, used in the treatment of colon cancer. KRAS mutation status is strongly predictive of cetuximab efficacy, but more predictive factors are needed for better patient selection. PTEN is a downstream inhibitor of the EGFR pathway and has been evaluated as a predictive factor of cetuximab efficacy in colorectal cancer. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor tissue samples were collected from 226 patients with advanced or metastatic colorectal cancer that had been treated with cetuximab. Clinical information was collected retrospectively from the patients' medical records. After central evaluation, 147 cases with adequate material were eligible for further evaluation. EGFR and PTEN status was evaluated with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Data were associated with cetuximab treatment outcome. Additional analysis was performed with previously published data on PIK3CA, BRAF and KRAS mutation status and EGFR ligand amphiregulin (AREG) and epiregulin intratumoral mRNA expression levels. PIK3CA mutation status and PTEN protein expression were also analyzed as a single complex parameter, to evaluate the predictive value of PI3K/PTEN axis dysfunction as one entity. RESULTS: Analysis showed a borderline association of overall response rate (ORR) and time to progression (TTP) with EGFR protein overexpression by IHC (p = 0.059 and p = 0.057, respectively) and a positive association of EGFR gain by FISH (found in only five cases) with longer TTP (p = 0.026). No association was found between ORR or TTP and PTEN IHC or FISH status. Comparative analysis with previously published data showed that PTEN protein expression is associated with longer TTP in patients with wild-type (WT) KRAS (p = 0.036) and especially in the ones with elevated AREG levels (p = 0.046), as well as in patients with both KRAS and BRAF WT (p = 0.019). Patients with both PIK3CA WT and PTEN protein expression had significantly longer TTP (p = 0.010) versus all others, in the absence of BRAF and KRAS mutations, a finding which persisted in the KRAS WT/AREG high subgroup (p = 0.046). CONCLUSIONS: In this cetuximab-treated colorectal cancer population, EGFR gain was associated with better outcome and PTEN protein expression with longer TTP in KRAS WT, KRAS WT/AREG high and KRAS/BRAF WT subpopulations. Cetuximab efficacy is greater with intact and activated EGFR signaling, without activating mutations of KRAS/BRAF and in the presence of preserved PTEN inhibitory activity upon the PI3K/AKT pathway. These results reflect a solid biological rationale and warrant further evaluation of the predictive role of PTEN in prospective studies.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/biossíntese , PTEN Fosfo-Hidrolase/biossíntese , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Biomarcadores Tumorais/genética , Cetuximab , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , PTEN Fosfo-Hidrolase/genética , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos
6.
J Transl Med ; 10: 10, 2012 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-22240029

RESUMO

BACKGROUND: HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy. METHODS: In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry). RESULTS: HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values < 0.001), but inconsistent patterns in the case of TOP2A. TOP2A gene amplification (7% of all cases) was not related to TOP2A mRNA and TopoIIa protein expression, while TOP2A mRNA and TopoIIa protein were strongly related to each other (p < 0.001). Hence, TOP2A amplified tumors did not correspond to tumors with high TOP2A mRNA or TopoIIa protein expression, while the latter were characterized by high Ki67 scores (p = 0.003 and p < 0.001, respectively). Multivariate analysis adjusted for nodal involvement, hormone receptor status, Ki67 score and HER2/TOP2A parameters revealed HER2/TOP2A co-amplification (21.2% of HER2 amplified tumors) as an independent favorable prognostic factor for DFS (HR = 0.13, 95% CI: 0.02-0.96, p = 0.046); in contrast, increased HER2/TOP2A mRNA co-expression was identified as an independent adverse prognostic factor for both DFS (HR = 2.41, 95% CI: 1.31-4.42, p = 0.005) and OS (HR = 2.83, 95% CI: 1.42-5.63, p = 0.003), while high TOP2A mRNA expression was an independent adverse prognostic factor for OS (HR = 2.06, 95% CI: 1.23-3.46, p = 0.006). None of the parameters tested was associated with response to paclitaxel. CONCLUSIONS: This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12611000506998.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/tratamento farmacológico , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epirubicina/uso terapêutico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Antibióticos Antineoplásicos/farmacologia , Antígenos de Neoplasias/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Epirubicina/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Neoplásicos/genética , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Inclusão em Parafina , Proteínas de Ligação a Poli-ADP-Ribose , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor ErbB-2/genética , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Fatores de Risco , Fixação de Tecidos , Resultado do Tratamento , Adulto Jovem
7.
Int Urol Nephrol ; 42(2): 325-30, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19655267

RESUMO

BACKGROUND: We aimed to determine whether a standard P504S, 34betaE12 and p63 immunostaining of prostate core needle biopsy specimens can optimize diagnostic accuracy of conventional staining methods. MATERIALS AND METHODS: The staining properties of all three antibodies were evaluated on 250 prostate biopsies formerly diagnosed as benign. RESULTS: Lack of basal cell staining in more than three glands for 34betaE12 and p63 occurred in 41 (27.5%) and 9 (6%) respective cases from the General Hospital pool. Respective figures from the Uropathology department specimens were 18 (18%) for 34betaE12 and 8 (8%) for p63. With the aid of P504S positivity, a case of prostate cancer as well as another of atypical small acinar proliferation was discovered. CONCLUSION: Despite its potential for important aid in accurate diagnosis, standard application of immunohistochemistry in prostate biopsy is not justified and should be reserved for equivocal cases where conventional pathology fails to be conclusive.


Assuntos
Queratinas/análise , Proteínas de Membrana/análise , Próstata/química , Próstata/patologia , Neoplasias da Próstata/química , Neoplasias da Próstata/patologia , Racemases e Epimerases/análise , Idoso , Biópsia por Agulha , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Coloração e Rotulagem
8.
Oncology ; 72(5-6): 388-96, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18187961

RESUMO

BACKGROUND: To assess the prognostic and predictive significance of HER-1/EGFR protein levels in high-risk patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy. METHODS: 595 high-risk breast cancer patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF). Disease-free survival (DFS) was the primary end point. HER-1/EGFR was assessed by immunohistochemistry (IHC) in 312 patients. RESULTS: HER-1/EGFR expression was detected in 54 of 312 patients (17%). Positive expression of HER-1/EGFR was significantly associated with negative receptor status (52 vs. 17%, p < 0.001), worse histological grade (70 vs. 45%, p = 0.001), HER-2 overexpression (46 vs. 27%, p = 0.01) and positive p53 expression (48 vs. 19%, p < 0.001). With a median follow-up of 7 years, the total number of relapses was 105 (34%), and the total number of deaths 69 (22%). The analysis for DFS provides significant evidence that the HER-1/EGFR effect on the risk of disease progression was different according to treatment (interaction p = 0.02). Regarding overall survival, a trend towards a significant difference for an interaction of HER-1/EGFR and treatment was found (p = 0.07). CONCLUSION: The present study demonstrated a differential effect of positive HER-1/EGFR expression in the two treatment groups, with HER-1/EGFR being a negative prognostic marker in the absence of paclitaxel.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/genética , Epirubicina/administração & dosagem , Genes erbB-1/genética , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Terapia Combinada , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
9.
J Clin Ultrasound ; 33(8): 424-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16240424

RESUMO

The uterus is an extremely rare location for a primary or metastatic melanoma. We describe the ultrasonographic appearance of a malignant melanoma of the uterus presenting clinically as a large mass in a 78-year-old woman. Transabdominal sonography revealed a solid uterine mass measuring 13 x 11.5 x 8.5 cm with inhomogeneous echotexture and bright internal echoes. The tumor showed a diffuse spread inside the uterine corpus, and the endometrium was not demonstrated ultrasonographically.


Assuntos
Melanoma/diagnóstico por imagem , Neoplasias Uterinas/diagnóstico por imagem , Idoso , Feminino , Humanos , Ultrassonografia
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