RESUMO
Gene expression in Arabidopsis is regulated by more than 1,900 transcription factors (TFs), which have been identified genome-wide by the presence of well-conserved DNA-binding domains. Activator TFs contain activation domains (ADs) that recruit coactivator complexes; however, for nearly all Arabidopsis TFs, we lack knowledge about the presence, location and transcriptional strength of their ADs1. To address this gap, here we use a yeast library approach to experimentally identify Arabidopsis ADs on a proteome-wide scale, and find that more than half of the Arabidopsis TFs contain an AD. We annotate 1,553 ADs, the vast majority of which are, to our knowledge, previously unknown. Using the dataset generated, we develop a neural network to accurately predict ADs and to identify sequence features that are necessary to recruit coactivator complexes. We uncover six distinct combinations of sequence features that result in activation activity, providing a framework to interrogate the subfunctionalization of ADs. Furthermore, we identify ADs in the ancient AUXIN RESPONSE FACTOR family of TFs, revealing that AD positioning is conserved in distinct clades. Our findings provide a deep resource for understanding transcriptional activation, a framework for examining function in intrinsically disordered regions and a predictive model of ADs.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Domínios Proteicos , Fatores de Transcrição , Ativação Transcricional , Arabidopsis/química , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/classificação , Proteínas de Arabidopsis/metabolismo , Sequência Conservada/genética , Conjuntos de Dados como Assunto , Regulação da Expressão Gênica de Plantas/genética , Ácidos Indolacéticos/metabolismo , Proteínas Intrinsicamente Desordenadas , Anotação de Sequência Molecular , Redes Neurais de Computação , Proteoma/química , Proteoma/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/classificação , Fatores de Transcrição/metabolismo , Ativação Transcricional/genéticaRESUMO
Some prion-like domains and low-complexity regions provide the multivalency required to facilitate protein phase separation to regulate protein function. Jung et al. (2020) demonstrate how natural selection of the ELF3 prion-like domain gives rise to an intuitive biological switch that directly responds to temperature.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Príons , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Príons/genética , Domínios Proteicos , Temperatura , Fatores de TranscriçãoRESUMO
Plants are exposed to a variety of abiotic stresses; these stresses have profound effects on plant growth, survival, and productivity. Tolerance and adaptation to stress require sophisticated stress sensing, signaling, and various regulatory mechanisms. The plant hormone auxin is a key regulator of plant growth and development, playing pivotal roles in the integration of abiotic stress signals and control of downstream stress responses. In this review, we summarize and discuss recent advances in understanding the intersection of auxin and abiotic stress in plants, with a focus on temperature, salt, and drought stresses. We also explore the roles of auxin in stress tolerance and opportunities arising for agricultural applications.
Assuntos
Ácidos Indolacéticos , Reguladores de Crescimento de Plantas , Plantas , Estresse Fisiológico/fisiologia , Desenvolvimento VegetalRESUMO
Deoxyribonucleic acid (DNA) has been hypothesized to act as a molecular wire due to the presence of an extended π-stack between base pairs, but the factors that are detrimental in the mechanism of charge transport (CT) across tunnel junctions with DNA are still unclear. Here we systematically investigate CT across dense DNA monolayers in large-area biomolecular tunnel junctions to determine when intrachain or interchain CT dominates and under which conditions the mechanism of CT becomes thermally activated. In our junctions, double-stranded DNA (dsDNA) is 30-fold more conductive than single-stranded DNA (ssDNA). The main reason for this large change in conductivity is that dsDNA forms ordered monolayers where intrachain tunneling dominates, resulting in high CT rates. By varying the temperature T and the length of the DNA fragments in the junctions, which determines the tunneling distance, we reveal a complex interplay between T, the length of DNA, and structural order on the mechanism of charge transport. Both the increase in the tunneling distance and the decrease in structural order result in a change in the mechanism of CT from coherent tunneling to incoherent tunneling (hopping). Our results highlight the importance of the interplay between structural order, tunneling distance, and temperature on the CT mechanism across DNA in molecular junctions.
Assuntos
DNA de Cadeia Simples/química , Condutividade Elétrica , Conformação de Ácido Nucleico , TemperaturaRESUMO
Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,Rp ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,Rp ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20â times less cytotoxic. On the other hand, methylated derivatives of 1-(S,Rp ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,Rp ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Compostos Ferrosos/farmacologia , Metalocenos/farmacologia , Nucleosídeos/farmacologia , Compostos Organometálicos/farmacologia , Osteossarcoma/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias Ósseas/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Ferrosos/química , Humanos , Metalocenos/química , Metilação , Modelos Moleculares , Estrutura Molecular , Nucleosídeos/química , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Osteossarcoma/patologia , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
OBJECTIVE: The aim of the study was to describe the clinical and histopathologic features required for a clinicopathologic diagnosis of vulvar lichen planus (LP), which is divided into 3 types: erosive, classic, and hypertrophic. MATERIALS AND METHODS: The International Society of the Study of Vulvovaginal Diseases tasked the Difficult Pathologic Diagnoses committee with development of a consensus document for the clinicopathologic diagnosis of vulvar LP, lichen sclerosus, and differentiated vulvar intraepithelial neoplasia. The LP subgroup reviewed the literature and formulated diagnostic criteria, then approved by the International Society of the Study of Vulvovaginal Diseases membership. RESULTS: The clinicopathologic diagnosis of erosive LP incorporates 5 criteria: (a) a well-demarcated, glazed red macule or patch at labia minora, vestibule, and/or vagina, (b) disease affects hairless skin, mucocutaneous junction, and/or nonkeratinized squamous epithelium, (c) evidence of basal layer damage, categorized as degenerative or regenerative, (d) a closely applied band-like lymphocytic infiltrate, and (e) absent subepithelial sclerosis. The clinicopathologic diagnoses of classic and hypertrophic LP each require a characteristic clinical appearance accompanied by hyperkeratosis, hypergranulosis, acanthosis, basal layer degeneration, a closely applied lymphocytic infiltrate, and absent dermal sclerosis, with hypertrophic LP showing marked epithelial abnormality compared with classic LP. CONCLUSIONS: Clinicopathological correlation yields the most reliable diagnosis of vulvar LP. Disease appearance overlaps with other physiologic, dermatologic, infectious, and neoplastic entities; a low threshold for biopsy at all morphologically distinct areas is recommended. Use of the histopathologic criteria described in this document may reduce the nondiagnostic biopsy rate for clinically diagnosed LP.
Assuntos
Líquen Escleroso e Atrófico/diagnóstico , Vagina/patologia , Vulva/patologia , Líquen Escleroso Vulvar/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Líquen Escleroso e Atrófico/patologia , Esclerose/patologia , Líquen Escleroso Vulvar/patologiaRESUMO
Endometrial thickness as measured by transvaginal ultrasound (TVUS) is being increasingly used as a first-line method to evaluate patients with vaginal bleeding. Our study aims to examine correlation between the histopathologic diagnosis and the results of TVUS and find a threshold that could reliably exclude carcinoma. We included women, age 55 years and above, who presented with postmenopausal bleeding and had a TVUS within 30 days of their endometrial biopsy. Total of 304 patients met our criteria and were divided into 4 groups. Patients in group A (n=198) had benign/atrophic endometrium, group B (n=44) had polyps, group C (n=30) had hyperplasia, and group D (n=32) had carcinoma. The endometrial thickness obtained by TVUS was compared with the histopathologic finding of the endometrial biopsy. The mean endometrial thickness was 7.5, 12.1, 14.8, and 16.9 mm for groups A to D, respectively. Statistical analysis showed that very low endometrial thickness (3 to 4 mm) would be ideal to use as a threshold to maximize sensitivity. Three of 32 patients in group D had an endometrial thickness ≤4 mm. At a threshold of 4 mm, the sensitivity is 90.6% and increases to 96.9% when decreasing the threshold to 3 mm. However, other parameters such as test accuracy, specificity, and positive predictive values are very low at these thresholds. Sensitivity can be maximized to 96.9% using a threshold of 3 mm. However, this would call into question the cost-effectiveness of this method. Postmenopausal bleeding remains the most reliable indicator of endometrial pathology.
Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Endométrio/diagnóstico por imagem , Pós-Menopausa/fisiologia , Ultrassonografia/métodos , Hemorragia Uterina/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Pólipos/patologia , Sensibilidade e EspecificidadeRESUMO
The "unfortunate experiment" that took place for a period of more than 20 years at the New Zealand Woman's Hospital in Auckland, New Zealand, had tragic results for numerous unsuspecting women and ultimately caused a 20-year setback in cervical cancer screening in New Zealand. The story of Herbert Green's evolving beliefs about cervical cancer, his pursuit of proof for his unfounded theory, based on "no more that a whim and misbelief" according to author Ron Jones, as well as the history of the active as well as passive complicity of superiors and colleagues for years in the rarified realm of academic medicine, is recounted in this engrossing and well-documented book.A historical account of an unfortunate experiment in cervical neoplasia diagnosis and management is presented.
Assuntos
Gerenciamento Clínico , Detecção Precoce de Câncer/ética , Detecção Precoce de Câncer/história , Neoplasias do Colo do Útero/diagnóstico , Feminino , História do Século XX , Humanos , Nova ZelândiaRESUMO
Tissue biopsy following a pap test diagnosis of high grade squamous intraepithelial lesion (HSIL) sometimes fails to confirm the presence of a corresponding high grade cervical intraepithelial lesion (CIN 2-3), leading to confusion as to how best to manage the patient. It has been shown that these patients are still at higher risk for future detection of CIN 2-3 even if the initial biopsy fails to detect it. It has also been shown that immunohistochemical staining for p16INK4a can be reliably used as a surrogate marker for infection with high risk human papillomavirus in cervical samples, and that it can be used to enhance detection of CIN2-3 in cases where suspicion is high. To evaluate the use of p16INK4a staining in cases of HSIL which were not confirmed on initial biopsy, two pathologists rereviewed Pap and hematoxylin and eosin preparations from all such cases seen within the preceding 3 years. Immunohistochemical study for p16INK4a was performed and graded on representative sections. The results were tabulated and analyzed. Of the identified 596 HSIL Pap cases, 82% had HSIL on initial cervical specimens. Table 1 shows the 56 cases included in the study with graded and stratified p16INK4a results. On review of the p16INK4a slides, only 2 cases could be upgraded to HSIL/CIN2-3 from the original diagnosis. p16INK4a 2-3+ was expressed more frequently in cases initially interpreted on Pap as low-grade cervical lesion as compared with benign (24 of 35 cases). In the younger than 24-yr-old group p16 2-3+ reactivity was more frequent in benign and low-grade cervical lesion/CIN1 groups (benign: 3 of 5 cases, and CIN1: 6 of 8), and p16 negative reactivity was not seen. p16INK4a was graded 0-1+ more frequently in specimens interpreted as benign in the older than 25 yr olds (10 of 16 cases). The study suggests some diagnostic benefit from the use of p16INK4a immunohistochemical study on cervical specimens from women with a HSIL Pap test without HSIL/CIN2-3 on original hematoxylin and eosin review.
Assuntos
Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Lesões Intraepiteliais Escamosas Cervicais/patologia , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos Retrospectivos , Esfregaço Vaginal , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to review the nearly 100-year evolution of terminology applicable to oncogenic human papillomavirus (HPV)-related vulvar intraepithelial squamous lesions and present current consensus terminology. METHODS: An extensive literature search of the English language was performed, which included articles that reviewed French and German publications, from 1922 to 2012. The database search was assisted by representatives of the American Society for Colposcopy and the College of American Pathologists as part of a comprehensive study and consensus effort to achieve unified terminology among gynecologists, dermatologists, pathologists, and other related experts to develop for reporting female and male lower genital and anal HPV related squamous lesions. This was done by the committee referred to as the "LAST" Committee. Some of the results and conclusions have been previously presented and published. This presentation is specifically related to vulvar squamous intraepithelial lesion (SIL)/vulvar intraepithelial neoplasia terminology. RESULTS: This work will review past terminology related to HPV-related vulvar SIL, beginning in 1922. The most current terminology will be presented as proposed by the LAST Committee and considered by the World Health Organization this year in accord with the US-Canadian Academy of Pathology. CONCLUSIONS: A consensus of terminology for HPV-related vulvar SIL has been sought for some time, and currently, some consensus has been achieved. The term "squamous intraepithelial lesion" is favored over "intraepithelial neoplasia." A 2-tier classification, of "high grade (HSIL)" or "low grade (LSIL)," is favored over a 3- or 4-tier classification. The application of this terminology will be discussed.
Assuntos
Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/terapia , Terminologia como Assunto , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/terapia , Feminino , Humanos , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias Vulvares/patologiaRESUMO
We conducted a study to determine prevalence of HPV types in oropharyngeal cancers in the United States and establish a prevaccine baseline for monitoring the impact of vaccination. HPV DNA was extracted from tumor tissue samples from patients in whom cancer was diagnosed during 1995-2005. The samples were obtained from cancer registries and Residual Tissue Repository Program sites in the United States. HPV was detected and typed by using PCR reverse line blot assays. Among 557 invasive oropharyngeal squamous cell carcinomas, 72% were positive for HPV and 62% for vaccine types HPV16 or 18. Prevalence of HPV-16/18 was lower in women (53%) than in men (66%), and lower in non-Hispanic Black patients (31%) than in other racial/ethnic groups (68%-80%). Results indicate that vaccines could prevent most oropharyngeal cancers in the United States, but their effect may vary by demographic variables.
Assuntos
Alphapapillomavirus/classificação , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Prevalência , Vigilância em Saúde Pública , Sistema de Registros , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: We conducted a baseline study of human papillomavirus (HPV) type prevalence in invasive cervical cancers (ICCs) using data from 7 cancer registries (CRs) in the United States. Cases were diagnosed between 1994 and 2005 before the implementation of the HPV vaccines. MATERIALS AND METHODS: Cancer registries from Florida, Kentucky, Louisiana, Michigan, Hawaii, Iowa, and Los Angeles, California identified eligible ICC cases and obtained sections from representative blocks of archived tumor specimens for DNA extraction. All extracts were assayed by linear array and, if inadequate or HPV negative, retested with INNO-LiPA Genotype test. Clinical and demographic factors were obtained from the CRs and merged with the HPV typing data to analyze factors associated with different types and with HPV negativity. RESULTS: A total of 777 ICCs were included in this analysis, with broad geographic, age, and race distribution. Overall, HPV was detected in 91% of cases, including 51% HPV-16, 16% HPV-18 (HPV-16-negative), and 24% other oncogenic and rare types. After HPV-16 and -18, the most common types were 45, 33, 31, 35, and 52. Older age and nonsquamous histology were associated with HPV-negative typing. CONCLUSIONS: This study provides baseline prevaccine HPV types for postvaccine ICC surveillance in the future. HPV-16 and/or -18 were found in 67% of ICCs, indicating the potential for vaccines to prevent a significant number of cervical cancers.
Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Técnicas de Genotipagem/métodos , Humanos , Pessoa de Meia-Idade , Epidemiologia Molecular , Prevalência , Sistema de Registros , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To prospectively evaluate a new non invasive device that combines fluorescence and reflectance spectroscopy in a population in women at risk for cervical dysplasia. METHODS: A total of 1607 women were evaluated with multimodal hyperspectroscopy (MHS), a painless test with extremely high spectral resolution. Subjects who were referred to colposcopy based on abnormal screening tests or other referral criteria underwent the MHS test and also had a sample taken for additional cytology and presence of high risk human papilloma virus (HPV) prior to undergoing biopsy. RESULTS: Sensitivity of MHS for cervical intraepithelial neoplasia (CIN) 2+ was 91.3% (252/276). Specificity, or the potential reduction in referrals to colposcopy and biopsy, was 38.9% (222/570) for women with normal or benign histology and 30.3% (182/601) for women with CIN1 histology. Two year follow-up data, collected for a subgroup of 804 women, revealed 67 interval CIN2+ that originally were diagnosed at enrollment as normal or CIN1. MHS identified 60 of these (89.6%) as positive for CIN2+ prior to their discovery during the two year follow-up period. CONCLUSIONS: MHS provides an immediate result at the point of care. Recently, the limitations of cytology have become more obvious and as a consequence greater emphasis is being placed on HPV testing for cervical cancer screening, creating a need for an inexpensive, convenient and accurate test to reduce false positive referrals to colposcopy and increase the yield of CIN2+ at biopsy. MHS appears to have many of the attributes necessary for such an application.
Assuntos
Espectrometria de Fluorescência/métodos , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Óptica e Fotônica/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Estudos Prospectivos , Análise Espectral/métodos , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) project was co-sponsored by the College of American Pathologists (CAP) and the American Society for Colposcopy and Cervical Pathology (ASCCP) and included 5 working groups; three work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted upon at the consensus meeting. The final approved recommendations standardize biologically-relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.
Assuntos
Neoplasias do Ânus , Infecções por Papillomavirus , Patologia Clínica , Terminologia como Assunto , Neoplasias Urogenitais , Feminino , Humanos , Masculino , Neoplasias do Ânus/patologia , Carcinoma in Situ/patologia , Colposcopia , Neoplasias de Células Escamosas/patologia , Infecções por Papillomavirus/patologia , Patologia Clínica/normas , Lesões Pré-Cancerosas/patologia , Padrões de Referência , Neoplasias Urogenitais/patologia , Revisões Sistemáticas como AssuntoRESUMO
OBJECTIVE: We describe a woman with a long-standing history of Paget disease involving the vulva and vagina, who was previously diagnosed with a high-grade squamous lesion, atypical glandular cells, and adenocarcinoma on various different yearly Pap tests. MATERIALS AND METHODS: This article is a case report of this patient and a review of the literature concerning the cytology of Paget disease. RESULTS: By reviewing Pap test cytology findings, Paget cells were identified as atypical cell groups with enlarged nuclei and occasional prominent nucleoli and further characterized by immunoreactivity to carcinoembryonic antigen and gross cystic disease fluid protein that distinguished them from high-grade squamous lesion. CONCLUSIONS: By enabling early diagnosis, regular surveillance, and identification of Paget cells by cytopathology, the Pap test becomes a valuable tool in identifying initial and recurrent Paget disease when it involves the vagina.
Assuntos
Doença de Paget Extramamária/patologia , Teste de Papanicolaou , Doenças Vaginais/patologia , Doenças da Vulva/patologia , Idoso , Feminino , Humanos , Doença de Paget Extramamária/diagnóstico , Doenças Vaginais/diagnóstico , Doenças da Vulva/diagnósticoRESUMO
OBJECTIVE: This study aimed to conduct a representative survey of human papillomavirus (HPV) prevalence and its genotype distribution in invasive anal cancer specimens in the United States. MATERIALS AND METHODS: Population-based archival anal cancer specimens were identified from Florida, Kentucky, Louisiana, and Michigan cancer registries and Surveillance, Epidemiology, and End Results (SEER) tissue repositories in Hawaii, Iowa, and Los Angeles. Sections from 1 representative block per case were used for DNA extraction. All extracts were assayed first by linear array and retested with INNO-LiPA if inadequate or HPV negative. RESULTS: Among 146 unique invasive anal cancer cases, 93 (63.7%) were from women, and 53 (36.3%) were from men. Human papillomavirus (any type) was detected in 133 cases (91.1%) and 129 (88.4%) contained at least 1 high risk-type, most (80.1%) as a single genotype. Human papillomavirus type 16 had the highest prevalence (113 cases, 77.4%); HPV types 6, 11, 18, and 33 were also found multiple times. Among HPV-16-positive cases, 37% were identified as prototype variant Ep, and 63% were nonprototypes: 33% Em, 12% E-G131G, 5% Af1, 4% AA/NA-1, 3% E-C109G, 3% E-G131T, 2% As, and 1% Af2. No significant differences in the distributions of HPV (any), high-risk types, or HPV-16/18 were seen between sex, race, or age group. CONCLUSIONS: The establishment of prevaccine HPV prevalence in the United States is critical to the surveillance of vaccine efficacy. Almost 80% of anal cancers were positive for the vaccine types HPV-16 or HPV-18, and in 70%, these were the only types detected, suggesting that a high proportion might be preventable by current vaccines.
Assuntos
Neoplasias do Ânus/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Angiomyofibroblastoma (AMF) is a benign mesenchymal tumor usually found in the vulva. We reviewed 70 cases of vulvar AMF that have been reported in the English-language literature and report 1 case of a pedunculated variant. Our case brings the total reported to 71 and is only the fourth pedunculated variant reported. METHODS: This 50-year-old woman presented to our gynecology clinic with a 1-year history of a left labial mass. It began as pea-sized, and rapidly grew to 12 cm in diameter. Physical examination demonstrated a 12-cm pedunculated soft mass arising from the left labia majora. The clinical diagnosis was aggressive angiomyxoma, and a simple excision was performed. The final pathology demonstrated AMF. The patient remains free from tumor at 4 years of follow-up. RESULTS: Seventy-one cases were summarized. The mean age at presentation was 45 years. The lesions were equally distributed between the left (52%) and right (48%). The most common clinical diagnosis was a Bartholin gland cyst (46%) or lipoma (15%). The mean duration of the lesion before seeking treatment was 29 months, and the mean diameter at presentation was 5.9 cm. All of the patients were treated with simple excision. The mean duration of follow-up was 37 months. There was 1 report of sarcomatous transformation 2 years after initial treatment. CONCLUSIONS: Angiomyofibroblastoma is a rare benign tumor that most often occurs in the vulva. Differential diagnosis may include aggressive angiomyxoma, Bartholin cyst, or lipoma. The treatment of choice is simple total excision, which is usually curative.
Assuntos
Angiomioma/diagnóstico , Neoplasias de Tecido Muscular/diagnóstico , Vulva/patologia , Neoplasias Vulvares/diagnóstico , Angiomioma/patologia , Angiomioma/cirurgia , Diagnóstico Diferencial , Feminino , Histocitoquímica , Humanos , Microscopia , Pessoa de Meia-Idade , Neoplasias de Tecido Muscular/patologia , Neoplasias de Tecido Muscular/cirurgia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaRESUMO
OBJECTIVE: The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. MATERIALS AND METHODS: Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin-stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. RESULTS: Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). CONCLUSIONS: Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.
Assuntos
Carcinoma in Situ/virologia , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias Vulvares/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Viral/genética , Feminino , Genótipo , Histocitoquímica , Humanos , Microscopia , Pessoa de Meia-Idade , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prevalência , Estados Unidos/epidemiologia , Proteínas Estruturais Virais/genéticaRESUMO
The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.
Assuntos
Carcinoma de Células Escamosas , Infecções por Papillomavirus , Guias de Prática Clínica como Assunto , Lesões Pré-Cancerosas , Neoplasias do Colo do Útero , Neoplasias Vaginais , Feminino , Humanos , Canal Anal/patologia , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/patologia , Colposcopia/normas , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/patologia , Lesões Pré-Cancerosas/classificação , Lesões Pré-Cancerosas/virologia , Padrões de Referência , Sociedades Médicas/normas , Terminologia como Assunto , Estados Unidos , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/patologia , Neoplasias Vaginais/classificação , Neoplasias Vaginais/patologia , Esfregaço Vaginal/normas , Vulva/patologia , Revisões Sistemáticas como AssuntoRESUMO
Protein interactions are the foundation of cell biology. For robust signal transduction to occur, proteins interact selectively and modulate their behavior to direct specific biological outcomes. Frequently, modular protein interaction domains are central to these processes. Some of these domains bind proteins bearing post-translational modifications, such as phosphorylation, whereas other domains recognize and bind to specific amino acid motifs. Other modules act as diverse protein interaction scaffolds or can be multifunctional, forming head-to-head homodimers and binding specific peptide sequences or membrane phospholipids. Additionally, the so-called head-to-tail oligomerization domains (SAM, DIX, and PB1) can form extended polymers to regulate diverse aspects of biology. Although the mechanism and structures of these domains are diverse, they are united by their modularity. Together, these domains are versatile and facilitate the evolution of complex protein interaction networks. In this review, we will highlight the role of select modular protein interaction domains in various aspects of plant biology.