RESUMO
Angiomatoid fibrous histiocytoma (AFH) is a rarely metastasizing neoplasm that typically occurs in the deep dermis and subcutis of the extremities of young patients, characterized by a t(2;22) translocation involving EWSR1 and CREB1. Because of its distinctive histologic features, the diagnosis of AFH is generally straightforward, although the immunohistochemistry (IHC) findings are relatively nonspecific. We recently encountered a case of primary cranial AFH that showed strong MUC4 IHC expression, which has not yet been reported previously. Prompted by this surprising finding, we investigated MUC4 expression in a series of AFH to evaluate this potential diagnostic pitfall. The expression of ALK by IHC, recently discovered in AFH, was also assessed in this study. We also analyzed EWSR1 rearrangement by fluorescence in situ hybridization using a dual color break-apart probe to confirm the diagnosis. The results showed MUC4 expression in 22.2% of AFH cases (4/18 cases), demonstrating a variable intensity of cytoplasmic staining. Most notably, one of the positive cases showed strong and diffuse expression. ALK IHC expression was observed in 17 of 18 cases (94.4%), usually in a diffuse and strong cytoplasmic pattern. EWSR1 rearrangement was demonstrated by fluorescence in situ hybridization in 81.2% of cases (13 of 16), including all the MUC4-positive cases. Our results indicate that although the significance of MUC4 expression in AFH is unknown, it is important to be aware that a subset of AFH can express the protein by IHC, expanding a variety of MUC4-positive mesenchymal tumors.
Assuntos
Histiocitoma Fibroso Benigno/metabolismo , Mucina-4/metabolismo , Adolescente , Adulto , Idoso , Quinase do Linfoma Anaplásico/metabolismo , Criança , Pré-Escolar , Feminino , Rearranjo Gênico , Histiocitoma Fibroso Benigno/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteína EWS de Ligação a RNA/genéticaRESUMO
Deregulation of microRNA expression plays a significant role in several cancer types including Burkitt lymphoma (BL). MicroRNA genes may be regulated through epigenetic mechanisms, such as specific histone modifications and/or DNA methylation of CpG islands in promoter regions, or by regions that are located next to microRNA genes. Given the regulatory role of MYC in miR29 expression, methylation as an additional mechanism for miR29 silencing was investigated. Methylation of miR29a/b/c in BL tumour samples and BL cell lines (BL41 and Raji) was assessed by pyrosequencing assay. BL cells were treated with 5aza2'deoxicitidine (decitabine) and evaluated for miR29a/b/c expression and methylation status. MYC, DNMT1 and DNMT3B protein expression were accessed by western blotting. For EpsteinBarr virus (EBV) microRNA (miR)BART6 inhibition, the cells were transiently transfected with antiBART65p. BL tumour samples and BL cell lines presented miR29a/b1 and miR29b2/c genes methylated in CpG sites located in both the promoter and enhancer regions. The treatment of BL cells with decitabine reduced methylation, induced miR29s expression and downregulated MYC protein levels in a dosedependent manner. Notably, inhibition of EBV miRBART65p combined with decitabine enhanced miR29 expression in an EBVBL cell line. In conclusion, the miR29a/b1 and miR29b2/c genes have methylated CpG sequences at promoter and enhancer regions that may contribute to the regulation of miR29 expression in BL tumours. The present findings indicated interplay between MYC and miR29 regulation, highlighting the potential role of EBVmiRNAs in miR29 regulation for BL pathogenesis.
Assuntos
Linfoma de Burkitt/patologia , Metilação de DNA , Elementos Facilitadores Genéticos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Criança , Pré-Escolar , Ilhas de CpG , Epigênese Genética , Feminino , Herpesvirus Humano 4/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Proteínas Proto-Oncogênicas c-myc/genética , Células Tumorais CultivadasRESUMO
PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression. BL cells were treated with 5-aza-2'-deoxycytidine (decitabine) and evaluated for miR29 expressions and methylation status. DNMT3B inhibition was performed by DNMT3B siRNA. RESULTS: Ectopic expression of miR-29s in BL cells decreased CDK6, DNMT3B, TCL1 and MCL-1 protein levels, but CDK6 and MCL-1 mRNA expression was unaffected by miR-29. Decitabine enhanced miR-29 expression levels and decreased CDK6 protein expression. Additionally, inhibition of DNMT3B by siRNA increased miR-29a/b expression. Notably, the miR-29a/b1 and miR-29b2/c promoter genes showed methylated CpG sequences that were demethylated after decitabine treatments. Furthermore, MYC-negative tumours had higher levels of miR-29 expression compared with MYC-translocated cases, suggesting that MYC regulates miR-29 in BL tumours. CONCLUSIONS: Our results suggest a significant role for miR-29s in BL pathogenesis in altering the expression of targets involved in critical cancer pathways, such as cell cycle control, apoptosis inhibition and DNA methylation. Moreover, methylation-mediated miR-29 epigenetic silencing may occur during BL development.
Assuntos
Apoptose/genética , Linfoma de Burkitt/genética , Proliferação de Células/genética , Metilação de DNA/genética , MicroRNAs/genética , Adolescente , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica/fisiologia , Humanos , Lactente , Recém-NascidoRESUMO
Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently, MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA cluster that suppresses chromatin regulatory genes and the apoptosis regulator Bim. However, the expression and prognostic impact of miR-17-92 members in pediatric BL (pBL) are unknown. Therefore, we investigated miR-17, miR-19a, miR-19b, miR-20, and miR-92a expression and prognostic impact in a series of 41 pBL samples. In addition, Bim protein expression was evaluated and compared to miR-17, miR-19a, miR-19b, miR-20, and miR-92a levels and patient outcomes. The expression of miR-17-92 members was evaluated by qPCR and Bim protein by immunohistochemistry. Log-rank test was employed to assess prognostic impact. We found that upregulated expression of miR-17 and miR-20a correlates with lack of pro-apoptotic Bim expression. Patients bearing tumors with upregulated miR-17 displayed decreased overall survival (OS), and multivariate analysis revealed that miR-17 was a significant predictor of shortened OS. Using hairpin inhibitors, we showed that inhibition of miR-17 resulted in enhanced Bim expression in a BL cell line overexpressing the miR-17-92 cluster. Our results describe for the first time miR-17, miR-19a, miR-19b, miR-20a, and miR-92a expression profiles in pBL. The prognostic impact of miR-17 should be validated in a larger series, and may provide new therapeutic avenues in the era of anti-miRNA therapy research. Additional functional studies are further required to understand the specific role of miR-17-92 cluster members in BL.
Assuntos
Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adolescente , Linfoma de Burkitt/metabolismo , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Seguimentos , Humanos , Masculino , MicroRNAs/biossíntese , Prognóstico , RNA Longo não CodificanteRESUMO
We have studied 22 cases of mammary lipophyllodes tumors (LPT), analyzing their clinicopathologic features along with available follow-up. All cases were tested for cytokeratins, S100 protein, and MDM2, and in selected cases for estrogen receptor, smooth muscle actin, bcl2, desmin, and myogenin. Patients were women aged 21 to 69 years (average, 45 years), and LPT size ranged from 1.6 to 30 cm (average, 9.7 cm). Microscopically, LPT segregated as follows: atypical lipoma-like tumor/well-differentiated liposarcoma (ALT/WDL), 8 cases; myxoid, 6; and pleomorphic/poorly differentiated/round cell, 8, including a case of dedifferentiated liposarcoma. Immunohistochemistry studies showed focal positive staining for S100 and CD34 in most ALT/WDL, and desmin and myogenin in 2 cases with evidence of rhabdomyoblastic differentiation. MDM2 positivity was focally seen in 1 case. Follow-up was available in 8 cases. Multiple recurrent tumors were seen in 2 patients, and metastatic disease to the lung was seen in 2 patients. In 4 patients with a follow-up between 2 and 15 years there was no evidence of recurrent or metastatic disease. Patients with ALT/WDL (2/2) were alive with no evidence of disease; 2 of 4 patients with myxoid liposarcoma component experienced tumor recurrence, whereas pleomorphic liposarcoma LPT pursued a less favorable course although only 1 patient died of the condition. Absence of MDM2 reactivity in most cases seems not as meaningful as in fatty tumors of somatic soft parts.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Lipoma/diagnóstico , Lipossarcoma/diagnóstico , Tumor Filoide/diagnóstico , Adulto , Idoso , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipoma/metabolismo , Lipoma/cirurgia , Lipossarcoma/metabolismo , Lipossarcoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tumor Filoide/metabolismo , Tumor Filoide/cirurgia , Proteínas Proto-Oncogênicas c-mdm2/genética , Adulto JovemRESUMO
BACKGROUND: Ductal carcinoma in situ is the last step preceding invasive ductal carcinoma in breast carcinogenesis. OBJECTIVE: We investigated the role of myoepithelial cells and epithelium characteristics as predictors of the risk of stromal invasion. METHODS: We selected 236 cases with initial diagnosis of DCIS followed by surgical ressection distributed in groups 1 (without invasion) and 2 (with invasive carcinoma). RESULTS: The risk of stromal invasion after a DCIS diagnosis in biopsy was associated to triple-negative profile and loss of CD10 expression by myoepithelial cells, and inversely associated with CK5/6 expression by neoplastic cells and high expression of Smooth Muscle Myosin Heavy Chain (SMMHC) by myoepithelial cells. CONCLUSIONS: A combination of characteristics of epithelial and myoepithelial cells in DCIS in biopsy specimens is related to the risk of stromal invasion.
Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/química , Carcinoma Intraductal não Infiltrante/patologia , Biomarcadores Tumorais , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Queratina-5/análise , Queratina-6/análise , Pessoa de Meia-Idade , Invasividade Neoplásica , Neprilisina/análise , Fenótipo , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Miosinas de Músculo Liso/análise , Microambiente TumoralRESUMO
BACKGROUND: Breast cancer in young women has different clinical and pathologic features and a more aggressive biological behavior when compared to breast cancers in older women. However, information is limited to the group of very young women (≤25 years). OBJECTIVES: The aim of the present study was to investigate the pathological characteristics of breast cancer in 149 Brazilian women who were ≤25 years old at the time of breast cancer diagnosis. MATERIALS AND METHODS: Tumor samples diagnosed between 2003 and 2009 were analyzed from the archives of the Bacchi Laboratory. RESULTS: In our series of 149 Brazilian women ≤25 years, 8.7% presented with in situ disease only. Of 136 invasive carcinomas, 91.9% were of the ductal type and 45.6% were of histological grade III. Overall, estrogen receptor (ER) was positive in 59.6% cases, and HER2 overexpression was detected in 32.8%. We also found a low prevalence of Luminal A cases and a high prevalence of Triple Negative cases. Statistical analysis showed that HER2 and basal-like groups had a lower overall survival expectation. Follow-up data showed high frequencies of regional lymph node metastasis, distant metastasis, and tumor-related deaths. CONCLUSION: The present study represents the largest series of breast cancer arising in women ≤25 years and establishes the main clinical, pathological, immunohistochemical and follow-up features of this population.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adolescente , Adulto , Brasil , Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Criança , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Gradação de Tumores , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto JovemRESUMO
MYC translocations are a defining feature of Burkitt lymphoma and a group of diffuse large B-cell lymphoma (DLBCL) with inferior outcome. However, the clinical relevance of MYC gene rearrangement and its relationship with MYC protein expression has not been well characterized in lymphomas. Tissue microarrays containing 1214 lymphomas were successfully evaluated by immunohistochemistry using anti-MYC clone Y69 and a dual-color break-apart fluorescence in situ hybridization probe to detect MYC gene rearrangements. Aggressive B-cell lymphomas including Burkitt lymphoma and DLBCL showed the highest level of MYC protein staining defined as staining in >50% of lymphoma cells. A significant proportion of plasmablastic, B-lymphoblastic and T-lymphoblastic, and extranodal NK/T-cell lymphomas also showed staining in >50% of cells, whereas only occasional plasma cell myeloma, mantle cell lymphoma, and classical Hodgkin lymphoma showed a high level of staining. Small B-cell lymphomas, when positive, showed MYC protein in <50% of cells. In aggressive B-cell lymphomas, MYC rearrangement and MYC immunohistochemistry showed a high concordance rate; however, some DLBCL and all T-cell and NK-cell lymphomas with MYC protein expression lacked MYC gene rearrangements. Our results provide a baseline for MYC protein expression in lymphomas and indicate that its expression is not specific to lymphoma subtypes, cell lineage, or expected clinical behavior and is highly variable. In addition, MYC protein expression is not necessarily correlated with MYC gene rearrangements and suggests the need for caution in the interpretation of MYC immunohistochemistry in the differential diagnosis of lymphomas.
Assuntos
Biomarcadores Tumorais , Rearranjo Gênico , Linfoma/química , Linfoma/genética , Proteínas Proto-Oncogênicas c-myc , Análise Serial de Tecidos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Amplificação de Genes , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma/classificação , Linfoma/patologia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas c-myc/análise , Proteínas Proto-Oncogênicas c-myc/genética , Análise Serial de Tecidos/métodosRESUMO
CDKN2A is a tumor suppressor gene critical in the cell cycle regulation. Little is known regarding the role of CDKN2A methylation in the pathogenesis of Burkitt lymphoma (BL). CDKN2A methylation was investigated using pyrosequencing in 51 tumor samples. p16(INK4a) mRNA and protein levels were measured using real-time PCR and immunohistochemistry, respectively. CDKN2A methylation was detectable in 72% cases. Nuclear expression of p16(INK4a) was not detected in 41% cases. There was an association between methylation and absence of CDKN2A mRNA (P=0.003). In conclusion, CDKN2A methylation occurs at a high frequency suggesting a role in BL pathogenesis and potential therapeutic implications.
Assuntos
Linfoma de Burkitt/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Metilação de DNA , DNA de Neoplasias/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Adolescente , Linfoma de Burkitt/genética , Linhagem Celular Tumoral , Pré-Escolar , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , RNA Mensageiro/genética , RNA Neoplásico/genéticaRESUMO
OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.
Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Vasos Linfáticos/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Antígeno Ca-125/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Metástase Linfática , Vasos Linfáticos/química , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Mucinas/análise , Neoplasias Ovarianas/química , Valores de Referência , Análise Serial de Tecidos , Carga Tumoral , Adulto JovemRESUMO
OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. .
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/secundário , Vasos Linfáticos/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/química , /análise , Diagnóstico Diferencial , Imuno-Histoquímica , Queratinas/análise , Metástase Linfática , Vasos Linfáticos/química , Glicoproteínas de Membrana/análise , Proteínas de Membrana/análise , Mucinas/análise , Neoplasias Ovarianas/química , Valores de Referência , Análise Serial de Tecidos , Carga Tumoral , Biomarcadores Tumorais/análiseRESUMO
BACKGROUND: To compare the distribution of the intrinsic molecular subtypes of breast cancer based on immunohistochemical profile in the five major geographic regions of Brazil, a country of continental dimension, with a wide racial variation of people. METHODS: The study was retrospective observational. We classified 5,687 invasive breast cancers by molecular subtype based on immunohistochemical expression of estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 proliferation index. Cases were classified as luminal A (ER and/or PR positive and HER2 negative, Ki-67 < 14%), luminal B (ER and/or PR positive, HER2 negative, and Ki-67 > 14%), triple-positive (ER and/or PR positive and HER2 positive), HER2-enriched (ER and PR negative, and HER2- positive), and triple-negative (TN) (ER negative, PR negative, and HER2- negative). Comparisons of the ages of patients and molecular subtypes between different geographic regions were performed. RESULTS: South and Southeast regions with a higher percentage of European ancestry and higher socioeconomic status presented with the highest proportion of luminal tumors. The North region presented with more aggressive subtypes (HER2-enriched and triple-negative), while the Central-West region predominated triple-positive carcinomas. The Northeast--a region with a high African influence--presented intermediate frequency of the different molecular subtypes. The differences persisted in subgroups of patients under and over 50 years. CONCLUSIONS: The geographic regions differ according to the distribution of molecular subtypes of breast cancer. However, other differences, beside those related to African ancestry, such as socioeconomic, climatic, nutritional, and geographic, have to be considered to explain our results. The knowledge of the differences in breast cancer characteristics among the geographic regions may help to organize healthcare programs in large countries like Brazil with diverse economic and race composition among different geographic regions.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Carcinoma/epidemiologia , Neoplasias de Mama Triplo Negativas/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , População Negra/estatística & dados numéricos , Brasil/epidemiologia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Epidemiologia Molecular , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/metabolismo , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
NUT carcinoma (NC) is a rare malignant neoplasm usually located in the midline, including the upper aerodigestive tract. NC is an aggressive and highly lethal type of carcinoma. It is defined by the rearrangement of the nuclear protein in the testis (NUT) gene on chromosome 15q14. In most cases, the NUT is involved in a balanced translocation with the BRD4 gene on chromosome 19p13.1, an event that creates a BRD4-NUT fusion gene. The relationship between the human papillomavirus (HPV), p16, and upper aerodigestive tract cancer has been long postulated. In this study, we evaluated the relationship of the p16 expression in 4 cases of NCs and its eventual association with HPV. All 4 cases presented typical histopathologic findings with nuclear positivity of the NUT protein and strong expression for p16. None of these cases, however, showed an association with HPV evaluated by polymerase chain reaction. Despite the expression of p16, this negative result for HPV indicates that HPV infection probably does not play a role in the pathogenesis of NC.
Assuntos
Carcinoma/genética , Neoplasias Pulmonares/genética , Neoplasias do Mediastino/genética , Neoplasias Nasofaríngeas/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Adulto , Carcinoma/diagnóstico , Carcinoma/patologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patologia , PapillomaviridaeRESUMO
OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Queratina-5/metabolismo , Queratina-6/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Análise Serial de TecidosRESUMO
OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. .
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/metabolismo , /metabolismo , /metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Imuno-Histoquímica , Invasividade Neoplásica/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , /metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Análise Serial de TecidosRESUMO
Follicular lymphoma is clinically heterogenous, and therefore necessitates the identification of prognostic markers to stratify risk groups and optimize clinical management. It is relatively rare in patients younger than 40 years, and the clinicopathologic characteristics and biological behavior in this age group are poorly understood. In the current study, samples from a cohort of 200 patients between 19 and 40 years were evaluated retrospectively with respect to clinical, histologic, and genetic features. These were then correlated with clinical outcome. The median age at presentation was 35 years with a slight female prepoderance (56%). Most of the cases are presented with nodal disease (90%). Concomitant follicular lymphoma and diffuse large B-cell lymphoma were observed in 7 (4%) patients. Immunohistologic studies showed the expression of CD10 (91%), BCL6 (97%), BCL2 (95%), MUM1/IRF4 (12%), MDM2 (17%), and CD23 (25%). BCL2 rearrangement was present in 74%, and BCL6 in 20%. The estimated overall survival of patients was 13 years (mean). The presence of anemia, elevated lactose dehydrogenase, bone marrow involvement, and high-risk follicular lymphoma international prognostic index correlated with adverse overall survival. Our findings revealed that follicular lymphoma in young adults demonstrate similarities with that of older adults, including the frequency of presentation at various anatomic sites, grade, and adverse prognostic factors.
Assuntos
Biomarcadores Tumorais/análise , Linfoma Folicular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Adulto , Fatores Etários , Biomarcadores Tumorais/genética , Análise por Conglomerados , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Modelos Logísticos , Linfonodos/química , Linfonodos/patologia , Linfoma Folicular/química , Linfoma Folicular/genética , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS: We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS: There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Valor Preditivo dos Testes , PrognósticoRESUMO
PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS:There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.
OBJETIVO: Comparar características prognósticas e preditivas entre os componentes in situ e invasivo de carcinomas ductais da mama. MÉTODOS: Selecionamos 146 amostras mamárias consecutivas com carcinoma ductal in situ (CDIS) associado com carcinoma invasivo (CI) adjacente. Avaliamos grau nuclear e a expressão imunoistoquímica de receptor de estrogênio (RE), receptor de progesterona (RP), receptor do fator de crescimento epidérmico humano 2 (HER2), citoqueratina 5/6 (CK5/6) e o receptor do fator de crescimento epidérmico (EGFR) em ambos componentes, in situ e invasor, e a porcentagem de células marcadas pelo Ki-67 no componente invasivo. CDIS e CI foram classificados nos tipos moleculares, determinados pelo perfil imunoistoquímico, como luminal (RE/RP-positivo/HER2-negativo), triplo-positivo (RE/RP/HER2-positivo), HER2-puro (RE/RP-negativo/HER2-positivo) e triplo-negativo (RE/RP/HER2-negativo). A discriminação entre luminal A e Luminal B não foi feita por motivos estatísticos. Correlações entre as categorias dos dois grupos foram feitas pelo método de correlação de Spearman. RESULTADOS: Houve significante associação entre grau nuclear (p<0,0001), expressão de RE/RP) (p<0,0001), superexpressão de HER2 (p<0,0001), expressão de EGFR (p<0,0001) e perfil molecular (p<0,0001) entre os componentes in situ e invasivo. CK5/6 mostrou distribuição distinta em CDIS e CI, apresentando significante associação com o fenótipo triplo-negativo em CI, mas uma associação negativa ente os CDIS. CONCLUSÕES:Nossos resultados sugerem que as características prognósticas e preditivas clássicas dos CI estão já determinadas no estágio pré-invasivo da doença. Entretanto, o papel da CK5/6 no carcinoma invasivo pode ser diferente daquele das lesões precursoras.