RESUMO
Children with Group 3 medulloblastoma (G3 MB) have a very poor prognosis, and many do not survive beyond 5 years after diagnosis. A factor that may contribute to this is the lack of available targeted therapy. Expression of protein lin-28 homolog B (LIN28B), a regulator of developmental timing, is upregulated in several cancers, including G3 MB, and is associated with worse survival in this disease. Here, we investigate the role of the LIN28B pathway in G3 MB and demonstrate that the LIN28B-lethal-7 (let-7; a microRNA that is a tumor suppressor)-lymphokine-activated killer T-cell-originated protein kinase (PBK; also known as PDZ-binding kinase) axis promotes G3 MB proliferation. LIN28B knockdown in G3-MB-patient-derived cell lines leads to a significant reduction in cell viability and proliferation in vitro and in prolonged survival of mice with orthotopic tumors. The LIN28 inhibitor N-methyl-N-[3-(3-methyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)phenyl]acetamide (1632) significantly reduces G3 MB cell growth and demonstrates efficacy in reducing tumor growth in mouse xenograft models. Inhibiting PBK using HI-TOPK-032 also results in a significant reduction in G3 MB cell viability and proliferation. Together, these results highlight a critical role for the LIN28B-let-7-PBK pathway in G3 MB and provide preliminary preclinical results for drugs targeting this pathway.
Assuntos
Neoplasias Cerebelares , Meduloblastoma , MicroRNAs , Humanos , Camundongos , Animais , Meduloblastoma/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias Cerebelares/genética , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/genéticaRESUMO
Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. Here, we show that Sox2+ tumor cells project cellular processes to ensheathe capillaries in mouse medulloblastoma (MB), a process that depends on the mechanosensitive ion channel Piezo2. MB develops a tissue stiffness gradient as a function of distance to capillaries. Sox2+ tumor cells perceive substrate stiffness to sustain local intracellular calcium, actomyosin tension, and adhesion to promote cellular process growth and cell surface sequestration of ß-catenin. Piezo2 knockout reverses WNT/ß-catenin signaling states between Sox2+ tumor cells and endothelial cells, compromises the BTB, reduces the quiescence of Sox2+ tumor cells, and markedly enhances the MB response to chemotherapy. Our study reveals that mechanosensitive tumor cells construct the BTB to mask tumor chemosensitivity. Targeting Piezo2 addresses the BTB and tumor quiescence properties that underlie treatment failures in brain cancer.
Assuntos
Neoplasias Encefálicas , beta Catenina , Camundongos , Animais , beta Catenina/metabolismo , beta Catenina/uso terapêutico , Células Endoteliais/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Encéfalo/metabolismo , Canais Iônicos/metabolismo , Barreira Hematoencefálica/metabolismoRESUMO
Ependymomas are rare central nervous system tumours that can arise in the brain's supratentorial region or posterior fossa, or in the spinal cord. In 1924, Percival Bailey published the first comprehensive study of ependymomas. Since then, and especially over the past 10 years, our understanding of ependymomas has grown exponentially. In this Review, we discuss the evolution in knowledge regarding ependymoma subgroups and the resultant clinical implications. We also discuss key oncogenic and tumour suppressor signalling pathways that regulate tumour growth, the role of epigenetic dysregulation in the biology of ependymomas, and the various biological features of ependymoma tumorigenesis, including cell immortalization, stem cell-like properties, the tumour microenvironment and metastasis. We further review the limitations of current therapies such as relapse, radiation-induced cognitive deficits and chemotherapy resistance. Finally, we highlight next-generation therapies that are actively being explored, including tyrosine kinase inhibitors, telomerase inhibitors, anti-angiogenesis agents and immunotherapy.
Assuntos
Ependimoma , Recidiva Local de Neoplasia , Biologia , Ependimoma/genética , Ependimoma/metabolismo , Ependimoma/terapia , Humanos , Oncogenes , Microambiente TumoralRESUMO
BACKGROUND: We aimed to explore gaps in the care of meningioma patients that could improve quality of care by better understanding symptoms experienced by patients at various stages of treatment, and afterwards. METHODS: A novel 19-item self-administered questionnaire was provided for patients with meningiomas to complete by the American Brain Tumor Association (ABTA) over a 3-month period. RESULTS: A total of 1852 unique respondents were included. Nearly one-third of all respondents felt they received insufficient information about meningiomas at initial diagnosis (N = 607, 32.9%) and 28.8% (N = 530) believed they received insufficient information about treatment options. In fact, 34.5% of respondents received the majority of their information from the internet and nonhealthcare professionals. The most common concerns after initial diagnosis were risks associated with surgery and/or treatment (36.5%) followed by how the tumor would impact daily life (25%) and the risk of tumor recurrence (12.4%). Respondents indicated that a list of resources available for patients with meningiomas (N = 597, 32.3%) would have been most beneficial in regards to their disease experience after their initial diagnosis. Moreover, we found that a substantial proportion of patients continued to report symptoms long after treatment, with fatigue being the most common compared to before treatment (38.2% vs. 57.7%, χ 2 = 128, P < .001). CONCLUSIONS: Patients with meningiomas exhibit symptoms that continue well after treatment with fatigue and cognitive impairments as the most bothersome. Moreover, patients report key communication gaps that can be addressed to improve their disease experience and care.
RESUMO
Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.
Assuntos
Ependimoma/genética , Ependimoma/metabolismo , Epigenoma/genética , Neoplasias Infratentoriais/genética , Neoplasias Infratentoriais/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular , Proliferação de Células/genética , Metilação de DNA/genética , Epigenômica/métodos , Histonas/genética , Histonas/metabolismo , Humanos , Lactente , Lisina/genética , Lisina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mutação/genéticaRESUMO
Medulloblastoma is the most common pediatric malignant brain tumor. Advances in molecular profiling have uncovered significant heterogeneity among medulloblastomas and led to the identification of four distinct subgroups (wingless [WNT], sonic hedgehog [SHH], group 3, and group 4) that represent distinct disease entities in both underlying biology and clinical characteristics. The rapidly expanding repertoire of tools to study developmental and cancer biology is providing a wealth of knowledge about these embryonal tumors and is continuously refining the understanding of this complex cancer. In this review, the history of discovery in medulloblastoma is discussed, setting a foundation to outline the current state of understanding of the molecular underpinnings of this disease, with a focus on genomic events that define the aforementioned subgroups and evolving areas of focus, such as the cell of origin of medulloblastoma and medulloblastoma subtypes. With these recent discoveries in mind, the current state of medulloblastoma treatment and clinical trials is reviewed, including a novel risk stratification system that accounts for the molecular biomarkers of patients with a high risk for refractory disease. Lastly, critical areas of focus for future basic science and clinical research on this disease are discussed, such as the complexities of medulloblastoma metastases and recurrence as well as the priorities and strategies to implement in future clinical trials.
Assuntos
Neoplasias Cerebelares/genética , Meduloblastoma/genética , Adulto , Distribuição por Idade , Biomarcadores Tumorais/genética , Proteínas de Transporte/genética , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/terapia , Criança , RNA Helicases DEAD-box/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Gerenciamento Clínico , Feminino , Genômica , Proteínas Hedgehog/genética , Histona Desmetilases/genética , Humanos , Lactente , Masculino , Meduloblastoma/epidemiologia , Meduloblastoma/terapia , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Fosfoproteínas Fosfatases/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Proteínas Repressoras/genética , Distribuição por Sexo , Receptor Smoothened/genética , Telomerase/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteínas Wnt/genética , Via de Sinalização Wnt/genética , beta Catenina/genéticaRESUMO
In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.
Assuntos
Neoplasias Cerebelares/genética , Proteínas Hedgehog/genética , Meduloblastoma/genética , RNA Nuclear Pequeno/genética , Adolescente , Adulto , Processamento Alternativo , Proteínas Hedgehog/metabolismo , Humanos , Mutação , Sítios de Splice de RNA , Splicing de RNARESUMO
Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin+ stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.
Assuntos
Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Evolução Molecular , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Transcrição Gênica , Animais , Neoplasias Cerebelares/classificação , Cerebelo/citologia , Cerebelo/embriologia , Cerebelo/metabolismo , Criança , Feminino , Feto/citologia , Glioma/classificação , Glioma/genética , Glioma/patologia , Humanos , Meduloblastoma/classificação , Meduloblastoma/genética , Meduloblastoma/patologia , Camundongos , Análise de Sequência de RNA , Análise de Célula Única , Fatores de Tempo , Transcriptoma/genéticaRESUMO
Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.
RESUMO
OBJECTIVE Combined endoscopic third ventriculostomy (ETC) and choroid plexus cauterization (CPC)-ETV/CPC- is being investigated to increase the rate of shunt independence in infants with hydrocephalus. The degree of CPC necessary to achieve improved rates of shunt independence is currently unknown. METHODS Using data from a single-center, retrospective, observational cohort study involving patients who underwent ETV/CPC for treatment of infantile hydrocephalus, comparative statistical analyses were performed to detect a difference in need for subsequent CSF diversion procedure in patients undergoing partial CPC (describes unilateral CPC or bilateral CPC that only extended from the foramen of Monro [FM] to the atrium on one side) or subtotal CPC (describes CPC extending from the FM to the posterior temporal horn bilaterally) using a rigid neuroendoscope. Propensity scores for extent of CPC were calculated using age and etiology. Propensity scores were used to perform 1) case-matching comparisons and 2) Cox multivariable regression, adjusting for propensity score in the unmatched cohort. Cox multivariable regression adjusting for age and etiology, but not propensity score was also performed as a third statistical technique. RESULTS Eighty-four patients who underwent ETV/CPC had sufficient data to be included in the analysis. Subtotal CPC was performed in 58 patients (69%) and partial CPC in 26 (31%). The ETV/CPC success rates at 6 and 12 months, respectively, were 49% and 41% for patients undergoing subtotal CPC and 35% and 31% for those undergoing partial CPC. Cox multivariate regression in a 48-patient cohort case-matched by propensity score demonstrated no added effect of increased extent of CPC on ETV/CPC survival (HR 0.868, 95% CI 0.422-1.789, p = 0.702). Cox multivariate regression including all patients, with adjustment for propensity score, demonstrated no effect of extent of CPC on ETV/CPC survival (HR 0.845, 95% CI 0.462-1.548, p = 0.586). Cox multivariate regression including all patients, with adjustment for age and etiology, but not propensity score, demonstrated no effect of extent of CPC on ETV/CPC survival (HR 0.908, 95% CI 0.495-1.664, p = 0.755). CONCLUSIONS Using multiple comparative statistical analyses, no difference in need for subsequent CSF diversion procedure was detected between patients in this cohort who underwent partial versus subtotal CPC. Further investigation regarding whether there is truly no difference between partial versus subtotal extent of CPC in larger patient populations and whether further gain in CPC success can be achieved with complete CPC is warranted.
Assuntos
Cauterização/métodos , Plexo Corióideo/cirurgia , Hidrocefalia/cirurgia , Neuroendoscopia/métodos , Terceiro Ventrículo/cirurgia , Ventriculostomia/métodos , Plexo Corióideo/patologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/epidemiologia , Lactente , Recém-Nascido , Masculino , América do Norte/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Terceiro Ventrículo/patologiaRESUMO
BACKGROUND: Citation classics represent the highest cited works in a field and are often regarded as the most influential literature. Analyzing thematic trends in citation classics across eras enables recognition of important historical advances within a field. We present the first analysis of the citation classics in neuro-oncology. METHODS: The Web of Science database was searched using terms relevant to "neuro-oncology." Articles with >400 citations were identified and the top 100 cited articles were evaluated. RESULTS: The top 100 neuro-oncology citation classics consisted of 43 clinical studies (17 retrospective, 10 prospective, 16 randomized trials), 43 laboratory investigations, 8 reviews/meta-analyses, and 6 guidelines/consensus statements. Articles were classified into 4 themes: 13 pertained to tumor classification, 37 to tumor pathogenesis/clinical presentation, 6 to imaging, 44 to therapy (15 chemotherapy, 10 radiotherapy, 5 surgery, 14 new agents). Gliomas were the most common tumor type examined, with 70 articles. There was a significant increase in the number of citation classics in the late 1990s, which was paralleled by an increase in studies examining tumor pathogenesis, chemotherapy, and new agents along with laboratory and randomized studies. CONCLUSIONS: The majority of citation classics in neuro-oncology are related to gliomas and pertain to tumor pathogenesis and treatment. The rise in citation classics in recent years investigating tumor biology, new treatment agents, and chemotherapeutics may reflect increasing scientific interest in nonsurgical treatments for CNS tumors and the need for fundamental investigations into disease processes.
Assuntos
Fator de Impacto de Revistas , Oncologia/tendências , Neurologia/tendências , Animais , Humanos , Oncologia/estatística & dados numéricos , Neurologia/estatística & dados numéricosRESUMO
The aim of the study was to establish if the null cell adenoma (NCA) forms a distinct subgroup with unique clinicopathological characteristics within the nonfunctioning pituitary adenoma group particularly in relation to the silent gonadotroph adenomas (SGAs). We identified 31 patients with the pathological diagnosis of NCA verified by routine histology and immunohistochemistry with distinct differentiation from SGAs by an established negative testing for SF-1 at the Toronto Western Hospital between December 2004 and August 2010. We reviewed their demographic data, clinical features, magnetic resonance imaging, and the histologic variables: MIB-1, FGFR4, and P27. We compared these to 63 SGAs identified within the same period. All the NCAs were macroadenomas with diameter ranging from 15-57 mm and tumor volumes between 1.95-53.5 mm(3). Preoperative cavernous sinus tumor growth was able to predict the presence of a residual after surgery (p = 0.023). Furthermore, preoperative cavernous sinus extension (p = 0.002) and negative P27 expression (p = 0.035) were able to independently predict the subsequent growth of the postoperative tumor residual. Comparing the NCA to SGA, we found that MIB-1 was higher in NCA (mean ± SD = 3.43 ± 2.76 %) compared to SGAs (mean ± SD = 2.49 ± 1.41 %) (p = 0.044). The preoperative and postoperative tumor volume doubling times (TVDTs) displayed a negative correlation in the SGA (r = -0.855, p = 0.002) while in the NCA, a positive correlation was evident (r = 0.718, p = 0.029). Our study suggests that the NCAs are a distinct group with differing behavioral characteristics from the SGAs. It also appears that the finding of cavernous sinus extension on preoperative imaging and a negative P27 expression on immunohistochemistry in NCAs may be valuable tools in predicting residual tumor growth which may impact on postoperative care.
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Adenoma/patologia , Linfócitos Nulos/patologia , Neoplasias Hipofisárias/patologia , Adenoma/diagnóstico , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.
Assuntos
Adenoma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Hipofisárias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adenoma/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Humanos , Neoplasias Hipofisárias/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidoresRESUMO
UNLABELLED: OBJECT.: While the use of endoscopic approaches has become increasingly accepted in the resection of pituitary adenomas, limited evidence exists regarding the success of this technique for patients with large and giant pituitary adenomas. This study reviews the outcomes of a large cohort of patients with large and giant pituitary adenomas who underwent endoscopic endonasal transsphenoidal surgery at the authors' institution and focuses on identifying factors that can predict extent of resection and hence aid in developing guidelines and indications for the use of endoscopic endonasal transsphenoidal surgery versus open craniotomy approaches to large and giant pituitary adenomas. METHODS: The authors reviewed 487 patients who underwent endoscopic endonasal transsphenoidal resection of sellar masses. From this group, 73 consecutive patients with large and giant pituitary adenomas (defined as maximum diameter ≥ 3 cm and tumor volume ≥ 10 cm(3)) who underwent endoscopic endonasal transsphenoidal surgery between January 1, 2006, and June 6, 2012, were included in the study. Clinical presentation, radiological studies, laboratory investigations, tumor pathology data, clinical outcomes, extent of resection measured by volumetric analysis, and complications were analyzed. RESULTS: The mean preoperative tumor diameter in this series was 4.1 cm and the volume was 18 cm(3). The average resection rate was 82.9%, corresponding with a mean residual volume of 3 cm(3). Gross-total resection was achieved in 16 patients (24%), near-total in 11 (17%), subtotal in 24 (36%), and partial in 15 (23%). Seventy-three percent of patients experienced improvement in visual acuity, while 24% were unchanged. Visual fields were improved in 61.8% and unchanged in 5.5%. Overall, 27 patients (37%) experienced a total of 32 complications. The most common complications were sinusitis (14%) and CSF leak (10%). Six patients underwent subsequent radiation therapy because of aggressive tumor histopathology. No deaths occurred in this cohort of patients. Statistically significant predictors of extent of resection included highest Knosp grade (p = 0.001), preoperative tumor volume (p = 0.025), preoperative maximum tumor diameter (p = 0.002), hemorrhagic component (p = 0.027), posterior extension (p = 0.001), and sphenoid sinus invasion (p = 0.005). CONCLUSIONS: Endoscopic endonasal transsphenoidal surgery is an effective treatment method for patients with large and giant pituitary adenomas, which results in high (> 80%) rates of resection and improvement in visual function. It is not associated with high rates of major complications and is safe when performed by experienced surgeons. The preoperative Knosp grade, tumor volume, tumor diameter, hemorrhagic components on MRI, posterior extension, and sphenoid sinus invasion may allow a prediction of extent of resection and in these patients a staged operation may be required to maximize extent of resection.
Assuntos
Adenoma/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Procedimentos Neurocirúrgicos/métodos , Nariz/cirurgia , Neoplasias Hipofisárias/cirurgia , Osso Esfenoide/cirurgia , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
CONTEXT: The factors associated with pituitary adenoma (PA) growth rate remain unclear. OBJECTIVE: The objective of the study was to establish whether the preoperative growth and extension pattern of PA can predict postoperative growth rate and recurrence in addition to whether the PA growth rate correlates with proliferation and growth factor expression. PATIENTS: One hundred fifty-three consecutive patients who underwent surgery for pituitary adenoma from 1999 to 2011 at Toronto Western Hospital were identified. MAIN OUTCOME MEASURES: The PA growth rate was measured both pre- and postoperatively, and its association with patient demographics, magnetic resonance imaging, and histolopathological parameters was determined. RESULTS: The preoperative growth rate was associated with age (P = .0001), suprasellar growth (P = .003), the presence of a cyst/hemorrhage (P = .004), the mindbomb homolog-1 (P = .005), fibroblast growth factor receptor-4 positivity (P = .047), and p27 negativity (P = .007). After surgery, there were 34.6% residual volumes, which were associated with older age (P = .038) and also with growth patterns including anterior, posterior, suprasellar, and cavernous sinus extension (P = .001); 43.3% of these residuals grew and postoperative growth rate was calculated. Pre- and postoperative growth rates were correlated (r = 0.497, P = .026). Postoperative growth rate was associated with age (P = .015) and gender (P = .017). CONCLUSIONS: Our data suggest that the growth rate of PAs are influenced by various patient- and tumor-specific characteristics including the age and sex of the patient, the specific subtype of PA, its hormonal activity, its immunohistochemical profile including the mindbomb homolog 1 labeling index status, and its preponderance for different growth directions relative to the pituitary fossa. Furthermore, the pre- and postoperative PA growth rates were correlated, suggesting that postoperative PA growth rates can be predicted, in part, by preoperative growth rates, thus better informing postoperative outcome.