RESUMO
Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.
Assuntos
Coinfecção , Infecções por Citomegalovirus , Citomegalovirus , Neoplasias das Glândulas Salivares , Glândulas Salivares , Humanos , Coinfecção/virologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Masculino , Feminino , Neoplasias das Glândulas Salivares/virologia , Pessoa de Meia-Idade , Adulto , Idoso , Glândulas Salivares/virologia , Glândulas Salivares/patologia , Adenoma/virologia , Idoso de 80 Anos ou mais , Carcinoma/virologia , DNA Viral/genética , DNA Viral/análise , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Penile cancer (PeCa) is a rare disease, but its incidence has increased worldwide, mostly in HPV+ patients. Nevertheless, there is still no targeted treatment for this carcinoma. OBJECTIVE: To predict the main signaling pathways involved in penile tumorigenesis and its potential drug targets. METHODS: Genome-wide copy number profiling was performed in 28 PeCa. Integration analysis of CNAs and miRNAs and mRNA targets was performed by DIANA-TarBase v.8. The potential impact of the miRNAs/target genes on biological pathways was assessed by DIANA-miRPath v.3.0. For each miRNA, KEGG pathways were generated based on the tarbase and microT-CDS algorithms. Pharmaco-miR was used to identify associations between miRNAs and their target genes to predict druggable targets. RESULTS: 269 miRNAs and 2,395 genes were mapped in cytobands with CNAs. The comparison of the miRNAs mapped at these cytobands and the miRNAs that were predicted to regulate the genes also mapped in these regions, resulted in a set of common 35 miRNAs and 292 genes. Enrichment pathway revealed their involvement in five top signaling pathways. EGFR and COX2 were identified as potential druggable targets. CONCLUSION: Our data indicate the potential use of EGFR and COX2 inhibitors as a target treatment for PeCa patients.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Infecções por Papillomavirus/genética , Neoplasias Penianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Carcinoma/virologia , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Variações do Número de Cópias de DNA , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/patologia , Neoplasias Penianas/virologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , RNA Mensageiro/metabolismo , Transdução de Sinais/genéticaRESUMO
Lymphoepithelial carcinoma of salivary glands (LECSG) are rare neoplasms, reported in endemic populations (southeastern Chinese) with a strong Epstein-Barr virus (EBV) association. A retrospective series comparing EBV status within an ethnically diverse population (endemic vs. non-endemic patients) has not been reported. Sixteen LECSG were equally distributed between males (n = 8) and females (n = 8) with a median age of 54 years (range 18 to 85 years) at initial diagnosis. Ten patients were white, 4 Asian, and 2 black. The patients typically presented with swelling or mass for an average of 11.6 months. Tumors affected only major salivary glands: parotid (n = 13); submandibular (n = 3). Tumors were an average of 2.9 cm (range 1.5 to 5.8 cm). Nine of 16 (56%) patients had cervical lymph node metastases at presentation. No patients had nasopharyngeal or oropharyngeal tumors. Microscopically, the tumors were widely infiltrative, characterized by large polygonal to spindled cells arranged in a syncytial, lattice-like network in a background of lymphoplasmacytic cells. The neoplastic cells showed an open-vesicular nuclear chromatin to a more basaloid-morphology, the latter showing hyperchromatic nuclei and less cytoplasm, while nearly all of the cases had associated lymphoepithelial lesions/sialadenitis. By in situ hybridization, 8 of 16 cases had a strong, diffuse EBER expression (4 of 4 Asians; 4 of 12 non-Asians), while with immunohistochemistry all cases tested were pan-cytokeratin, CK5/6 and p63 reactive; none of the cases tested were p16 reactive. All patients were managed with wide or radical excision, 4 with concurrent chemoradiation, and 6 with radiation alone. Distant metastasis (lung, brain, and bone) developed in 2 patients. Overall follow-up (mean 3.8 years) revealed 12 patients alive and 2 dead, none with evidence of disease (mean 4.3 years); one white male alive with disease at 1.9 years, and one Asian female dead of disease at 4.2 years; both of these latter patients had Group IV stage disease. High stage (Group IV) patients had a shorter mean survival than lower stage patients: 3.1 versus 4.8 years, respectively. In conclusion, LECSG are uncommon primary neoplasms. Concurrent lymphoepithelial lesions may help suggest a primary tumor. The tumors, irrespective of race or ethnicity, may express EBER. There is an overall good survival, perhaps better for EBV-negative patients and for those with lower stage disease.
Assuntos
Carcinoma/epidemiologia , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/epidemiologia , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , América Central/epidemiologia , Doenças Endêmicas , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Multiple infections by HPV genotypes are frequently detected in HPV+ cervical lesions but the interaction between each viral genotype during carcinogenesis is poorly understood. Here we carried out a comprehensive study to characterize the multiple HPV expression and integration by RNA-seq analyses of 19 invasive cervical carcinomas coinfected by several HPV genotypes. Analysis of tumor DNA by a hybridization assay indicated multiple infections ranging from 2 to 6 different HPV genotypes. RNA-seq analysis showed that a single HPV genotype was preferentially expressed. Finally, the search for HPV/human chimeric transcripts indicated integration from preferentially expressed genotypes. In conclusion, the present study indicated that, in invasive cervical carcinomas infected by multiple HPV genotypes, one HPV was preferentially expressed, supporting the hypothesis that a single HPV genotype was associated with cancer development.
Assuntos
Carcinoma/virologia , Coinfecção/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Feminino , Genótipo , Humanos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/metabolismo , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/complicações , Splicing de RNA , Integração ViralRESUMO
BACKGROUND: Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV), particularly the undifferentiated nonkeratinizing subtype. Prevalence of EBV in NPC in countries such as Guatemala and Brazil has not been studied. METHODS: We analyzed 19 cases of NPC, 11 from Guatemala and 8 from Brazil, for the presence of EBV by in situ hybridization and immunohistochemistry. Additionally, 19 hyperplastic adenoids from children were analyzed for EBV by in situ hybridization, 12 from Guatemala and 7 from Brazil. RESULTS: All the NPC cases from Guatemala and 5 from Brazil were of the undifferentiated nonkeratinizing type. EBV-negative cases comprised 2 keratinizing NPC and 1 differentiated nonkeratinizing NPC. All undifferentiated nonkeratinizing NPC from both samples showed intense positivity for EBER, while LMP-1 only focally and scarcely expressed. EBER was positive in 75% and 43% of the adenoids from Guatemala and Brazil, respectively. CONCLUSIONS: All undifferentiated nonkeratinizing NPC irrespective of origin from Guatemala or Brazil were highly associated with EBV.
Assuntos
Carcinoma/virologia , Infecções por Vírus Epstein-Barr/epidemiologia , Neoplasias Nasofaríngeas/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Feminino , Guatemala/epidemiologia , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Adulto JovemRESUMO
BACKGROUND: HPV 16 is the cause of cervical carcinoma, but only a small fraction of women with HPV infection progress to this pathology. Besides persistent infection and HPV integration, several studies have suggested that HPV intratype variants may contribute to the development of cancer. The purpose of this study was to investigate the nucleotide variability and phylogenetically classify HPV 16 E6 variants circulating over a period of 16 years in women from Southern Mexico, and to analyze its association with precursor lesions and cervical carcinoma. METHODS: This study was conducted in 330 cervical DNA samples with HPV 16 from women who were residents of the State of Guerrero, located in Southern Mexico. According of cytological and/or histological diagnosis, samples were divided into the following four groups: no intraepithelial lesion (n = 97), low-grade squamous intraepithelial lesion (n = 123), high-grade squamous intraepithelial lesion (n = 19) and cervical carcinoma (n = 91). HPV 16 E6 gene was amplified, sequenced and aligned with reference sequence (HPV 16R) and a phylogenetic tree was constructed to identify and classify HPV 16 variants. Chi squared was used and data analysis and statistics were done with SPSS Statistics and STATA softwares. RESULTS: Twenty seven HPV 16 E6 variants were detected in women from Southern Mexico, 82.12% belonged to the EUR, 17.58% to AA1 and 0.3% to Afr2a sublineages. The most common was E-G350 (40%), followed by E-prototype (13.03%), E-C188/G350 (11.82%), AA-a (10.61%), AA-c (6.07%) and E-A176/G350 (5.15%). Eight new E6 variants were found and 2 of them lead to amino acid change: E-C183/G350 (I27T) and E-C306/G350 (K68T). The HPV 16 variant that showed the greatest risk of leading to the development of CC was AA-a (OR = 69.01, CI = 7.57-628.96), followed by E-A176/G350 (OR = 39.82, CI = 4.11-386.04), AA-c (OR = 21.16, CI 2.59-172.56), E-G350 (OR = 13.25, CI = 2.02-87.12) and E-C188/G350 (OR = 10.48, CI = 1.39-78.92). CONCLUSIONS: The variants more frequently found in women with cervical carcinoma are E-G350, AA-a, AA-c, E-C188/G350 and E-A176/G350. All of them are associated with the development of cervical carcinoma, however, AA-a showed the highest association. This study reinforces the proposal that HPV 16 AA-a is an oncogenic risk for cervical carcinoma progression in Mexico.
Assuntos
Carcinoma/virologia , Papillomavirus Humano 16/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Carcinoma/patologia , Feminino , Papillomavirus Humano 16/classificação , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiologia , Humanos , México , Dados de Sequência Molecular , Infecções por Papillomavirus/patologia , Filogenia , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach with dense lymphocytic infiltration. More than 80% of LELGCs are positive for the Epstein-Barr virus (EBV). Here, we report a 64-year old Chinese man with swallowing discomfort while eating food. Endoscopy and computed tomography both showed a submucosal lesion at the lesser curvature of the upper gastric body. The first diagnostic impression was a gastrointestinal stromal tumour. Subsequently, the patient received a wedge resection of the stomach. On histopathological examination, the tumour was found to consist of small nests of neoplastic cells within dense lymphocytic infiltration. Additionally, most of the neoplastic cells were positive for cytokeratin and Epstein-Barr virus-encoded RNA (EBER). Subsequently, the diagnosis of LELGC was made. We believe that physicians should be aware of the diagnosis of submucosal gastric lesions, particularly in older male patients.
El carcinoma gástrico de tipo linfoepitelioma (CGLE) es una neoplasia rara del estómago con una infiltración linfocítica densa. Más del 80% de los CGLEs son positivos al virus de Epstein-Barr (EBV). Aquí reportamos el caso de un paciente chino de 64 años, que sentía malestar al efectuar la deglución de alimentos. Tanto la endoscopia como la tomografía computarizada mostraron una lesión submucosa en la curvatura menor de la parte superior del cuerpo gástrico. La primera impresión diagnóstica fue de un tumor del estroma gastrointestinal Posteriormente, al paciente se le hizo una resección en cuña del estómago. En el examen histopatológico, se halló que el tumor consistía de pequeños nidos de células neoplásicas dentro de una infiltración linfocítica densa. Además, la mayoría de las células neoplásicas eran positivas a la citoqueratina y al ARN codificado por el virus de Epstein-Barr (EBER). Posteriormente, se realizó el diagnóstico de CGLE. Creemos que los médicos deben tomar conciencia del diagnóstico de las lesiones submucosas gástricas, especialmente en los pacientes mayores hombres.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico , Carcinoma/diagnóstico , Herpesvirus Humano 4/genética , Neoplasias Gástricas/virologia , RNA Viral/análise , Carcinoma/virologia , Linfócitos/patologiaRESUMO
Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV-related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16 expression.
Assuntos
Neoplasias do Ânus/virologia , Carcinoma/virologia , DNA Viral/análise , Neoplasias dos Genitais Femininos/virologia , Neoplasias dos Genitais Masculinos/virologia , Testes de DNA para Papilomavírus Humano/métodos , Papillomavirus Humano 11/genética , Papillomavirus Humano 6/genética , Microdissecção e Captura a Laser , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Adulto , Idoso , Neoplasias do Ânus/química , Neoplasias do Ânus/patologia , Biomarcadores Tumorais/análise , Biópsia , Carcinoma/química , Carcinoma/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Sondas de DNA de HPV , Feminino , Neoplasias dos Genitais Femininos/química , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/química , Neoplasias dos Genitais Masculinos/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVES: To evaluate the prevalence, distribution and association of HPV with histological pattern of worse prognosis of penile cancer, in order to evaluate its predictive value of inguinal metastasis, as well as evaluation of other previous reported prognostic factors. MATERIAL AND METHODS: Tumor samples of 82 patients with penile carcinoma were tested in order to establish the prevalence and distribution of genotypic HPV using PCR. HPV status was correlated to histopathological factors and the presence of inguinal mestastasis. The influence of several histological characteristics was also correlated to inguinal disease-free survival. RESULTS: Follow-up varied from 1 to 71 months (median 22 months). HPV DNA was identified in 60.9% of sample, with higher prevalence of types 11 and 6 (64% and 32%, respectively). There was no significant correlation of the histological characteristics of worse prognosis of penile cancer with HPV status. Inguinal disease-free survival in 5 years did also not show HPV status influence (p = 0.45). The only independent pathologic factors of inguinal metastasis were: stage T ≥ T1b-T4 (p = 0.02), lymphovascular invasion (p = 0.04) and infiltrative invasion (p = 0.03). CONCLUSIONS: HPV status and distribution had shown no correlation with worse prognosis of histological aspects, or predictive value for lymphatic metastasis in penile carcinoma.
Assuntos
Carcinoma/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Neoplasias Penianas/patologia , Neoplasias Penianas/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Carcinoma/patologia , Carcinoma/secundário , Intervalo Livre de Doença , Humanos , Canal Inguinal , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
The role of human papillomavirus (HPV) infection in penile carcinoma (PeC) is currently reported and about half of the PeC is associated with HPV16 and 18. We used a PCR-based strategy by using HPV general primers to analyze 86 penile carcinomas paraffin-embedded tissues. Some clinical data, the histological subtype, growth pattern, and differentiation degree were also collected. The amplified fragments were then sequenced to confirm the HPV type and for HPV16/18 variants. DNA samples were also subjected to relative real time PCR for hTERC gene copy number. Some clinical data were also collected. Global HPV frequency was 77.9%. Relative contributions was for HPV16 (85%), 31 (4.4%), 11 (4.4%), 58, 33, 18, and 59 (1.4% each one). Sequence analysis of HPV16 identified European variants and Asian-American (AAb-c) variants in 92% and in 8% of the samples, respectively. Furthermore hTERC gene amplification was observed in only 17% of the cases. Our results suggest that some members of HPV A9 group (represented by HPV16, 58, and 31) are the most frequent among PeC patients studied with an important contribution from HPV16 European variant. The hTERC gene amplification could be poorly related to penile epithelial tissue.