RESUMO
The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.
Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc , Proteínas RGS , Neoplasias Gástricas , Humanos , Proteínas RGS/genética , Proteínas RGS/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Reparo de Erro de Pareamento de DNA , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/genéticaRESUMO
BACKGROUND: Brain metastasis is a common outcome in non-small cell lung cancer, and despite aggressive treatment, its clinical outcome is still frustrating. In recent years, immunotherapy has been developing rapidly, however, its therapeutic outcomes for primary lung cancer and brain metastases are not the same, suggesting that there may be differences in the immune microenvironment of primary lung cancer and brain metastases, however, we currently know little about these differences. METHODS: Seventeen paired samples of NSCLC and their brain metastases and 45 other unpaired brain metastases samples were collected for the current study. Immunohistochemical staining was performed on all samples for the following markers: immune checkpoints CTLA-4, PD-1, PD-L1, B7-H3, B7-H4, IDO1, and EphA2; tumor-infiltrating lymphocytes (TILs) CD3, CD4, CD8, and CD20; tumor-associated microglia/macrophages (TAMs) CD68 and CD163; and tumor proliferation index Ki-67. The differences in expression of these markers were compared in 17 paired samples, and the effect of the expression level of these markers on the prognosis of patients was analyzed in lung adenocarcinoma brain metastases samples. Subsequently, multiplex immunofluorescence staining was performed in a typical lung-brain paired sample based on the aforementioned results. The multiplex immunofluorescence staining results revealed the difference in tumor immune microenvironment between primary NSCLC and brain metastases. RESULTS: In 17 paired lesions, the infiltration of CTLA-4+ (P = 0.461), PD-1+ (P = 0.106), CD3+ (P = 0.045), CD4+ (P = 0.037), CD8+ (P = 0.008), and CD20+ (P = 0.029) TILs in brain metastases were significantly decreased compared with primary tumors. No statistically significant difference was observed in the CD68 (P = 0.954) and CD163 (P = 0.654) TAM infiltration between primary NSCLC and paired brain metastases. In all the brain metastases lesions, the expression of PD-L1 is related to the time interval of brain metastases in NSCLC. In addition, the Cox proportional hazards regression models showed high expression of B7-H4 (hazard ratio [HR] = 3.276, 95% confidence interval [CI] 1.335-8.041, P = 0.010) and CD68 TAM infiltration (HR = 3.775, 95% CI 1.419-10.044, P = 0.008) were independent prognosis factors for lung adenocarcinoma brain metastases patients. CONCLUSIONS: Both temporal and spatial heterogeneity is present between the primary tumor and brain metastases of NCSLC. Brain metastases lesions exhibit a more immunosuppressive tumor immune microenvironment. B7-H4 and CD68+ TAMs may have potential therapeutic value for lung adenocarcinoma brain metastases patients.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Antígeno CTLA-4 , Receptor de Morte Celular Programada 1 , Microambiente TumoralRESUMO
We aimed to detect the clinicopathological features and immune microenvironment of double-hit/triple-hit lymphoma in the gastrointestinal tract (GI-DHL/THL) and identify the best diagnostic strategies. A total of 114 cases, including 15 GI-DHL/THL, 42 non-GI-DHL/THL and 57 control diffuse large B-cell lymphoma (DLBCL) cases, were comparatively analyzed for their clinicopathological characteristics, the expression of the immune-regulatory checkpoint PD-L1 and immune microenvironment. We applied univariate and multivariate analyses to determine predictors of DHL/THL. GI-DHL/THL patients showed a higher prevalence of previous infection with hepatitis B virus (HBV) than those with GI-DLBCL. Morphologically, 87% of cases exhibited features of DLBCL. Regarding immunohistochemistry results, the MYC protein expression and the Ki-67 proliferation index were significantly higher in the GI-DHL/THL group than in the GI-DLBCL group. The main source of PD-L1 expression in DHL was tumor-associated macrophages, whereas some tumor cells were positive for PD-L1 in GI-DLBCL cases, as determined through multiplex immunofluorescence staining. The multivariable logistic analysis suggested that 5 variables, namely, age, Mum1, CD10, MYC, and HBV infection status, reflect the risk of DHL/THL. The GI-DHL/THL group show different clinicopathological features and immune microenvironments from DLBCL, which might suggest that different signaling pathways are involved. More work is needed to elucidate the pathogenic mechanism of GI-DHL/THL.
Assuntos
Antígeno B7-H1 , Linfoma Difuso de Grandes Células B , Humanos , Antígeno Ki-67 , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Imuno-Histoquímica , Trato Gastrointestinal/patologia , Proteínas Proto-Oncogênicas c-myc , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas c-bcl-6 , Microambiente TumoralRESUMO
Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed postmortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients' ages ranged from 59 to 81, including three males and one female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the postmortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.
Assuntos
Infecções por Coronavirus/patologia , Fígado/patologia , Pulmão/patologia , Miocárdio/patologia , Pneumonia Viral/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biópsia com Agulha de Grande Calibre , COVID-19 , China , Infecções por Coronavirus/complicações , Feminino , Fibrose , Humanos , Hipertrofia , Imuno-Histoquímica , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/patologia , Contagem de Leucócitos , Pulmão/diagnóstico por imagem , Linfopenia/patologia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Radiografia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios XRESUMO
Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syndrome. NexGen sequencing identified a frame-shift mutation in the MSH2 gene. The patient was found to have a metachronous colorectal carcinoma, uterine endometrial carcinoma, and skin cancer from 1998 to 2016. Five family members had also suffered from colorectal cancer or glioma. This case report illustrates the importance of the multidisciplinary care approach, mismatch repair protein and gene testing, and detailed medical history taking into consideration the diagnosis of Muir-Torre syndrome.
Assuntos
Síndrome de Muir-Torre/genética , Proteína 2 Homóloga a MutS/genética , Feminino , Mutação da Fase de Leitura , Humanos , Pessoa de Meia-Idade , Síndrome de Muir-Torre/patologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologiaRESUMO
INTRODUCTION: To systematically analyze CT and clinical characteristics to find out the risk factors of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC). Then the significant characteristics were used to set up a mathematic model to predict EGFR mutation in NSCLC. MATERIALS AND METHODS: PubMed, Web of Knowledge and EMBASE up to August 17, 2018 were systematically searched for relevant studies that investigated the evidence of association between CT and clinical characteristics and EGFR mutation in NSCLC. After study selection, data extraction, and quality assessment, the pooled odds ratios (ORs) were calculated. Then from May 2017 to August 2018, all NSCLC received EGFR mutation examination and CT examination in our hospital were chosen to test the prediction model by receiver operating characteristic (ROC) curves. RESULTS: Seventeen original studies met the inclusion criteria. The results showed that the ORs of ground-glass opacity (GGO), air bronchogram, pleural retraction, vascular convergence, smoking history, female gender were, respectively, 1.93 (P = 0.003), 2.09 (P = 0.03), 1.59 (P < 0.01), 1.61 (P = 0.001), 0.28 (P < 0.01), 0.35 (P < 0.01). The result of speculation, cavitation/bubble-like lucency, lesion shape, margin, pathological stage were, respectively, 1.19 (P = 0.32), 0.99 (P = 0.97), 0.82 (P = 0.42), 1.02 (P = 0.90), 0.77 (P = 0.30). 121 NSCLC received EGFR mutation test were included to test the prediction model. The mathematical model based on the results of meta-analysis was: 0.74 × air bronchogram + 0.46 × pleural retraction + 0.48 × vascular convergence - 1.27 × non-smoking history - 1.05 × female. The area under the ROC curve was 0.68. CONCLUSION: Based on the current evidence, GGO presence, air bronchogram, pleural retraction, vascular convergence were significant risk factors of EGFR mutation in NSCLC. And the prediction model can help to predict EGFR mutation status.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Tomografia Computadorizada por Raios X/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Curva ROCRESUMO
BACKGROUND: To analyse the differences in computed tomography (CT) features between patients with lung adenocarcinoma who have epidermal growth factor receptor (EGFR) mutations and those who have wild-type EGFR. METHODS: Patients with lung adenocarcinoma (n = 156) were enrolled from October 2013 to March 2016, including 56 patients with wild-type EGFR and 100 patients with EGFR mutations. Two independent radiologists evaluated patient characteristics and imaging features. Chi-squared test, Fisher's exact test or ANOVA was applied to discriminate clinical and CT characteristics between the genotypes. A prediction tool for EGFR mutation was devised from principal component analysis. RESULTS: The proportion of females and non-smokers in the exon 19 deletion and exon 21 missense groups was higher than in the wild-type group (P < 0.01). Severe emphysema was higher in the wild-type group than in the exon 19 deletion group (P < 0.01). The maximum diameter in the mediastinal window (MaxDmediastinal) in the wild-type group was longer than in the exon 19 deletion and exon 21 missense groups. The minimum diameter in the mediastinal window (MinDmediastinal) in the wild-type group was also longer than in the exon 21 missense group, with a significant difference (P < 0.05). The tumor shadow disappearance rate (TDR) in the exon 19 deletion group was higher than in the wild-type group. Ground glass opacity (GGO) appeared to be more common in the exon 19 deletion group (P = 0.010). The prediction score for exon 19 deletion mutation was: 0.305 × gender + 0.254 × smoking history + 0.198 × MaxDmediastinal + TDR × 0.254 + 0.280 × GGO + 0.095 × emphysema. The sensitivity and specificity for predicting exon 19 deletion were 59.09 and 76.79%, respectively. The prediction score for the exon 21 missense mutation was: 0.354 × gender + 0.291 × smoking history + 0.410 × MaxDmediastinal + 0.408 × MinDmediastinal. The sensitivity and specificity for predicting exon 21 missense mutation were 72.34 and 78.57%, respectively. CONCLUSION: As well as gender, smoking history and GGO, adenocarcinomas with EGFR mutation were significantly associated with emphysema, TDR, and the diameter in the mediastinal window. As exon 19 deletion and 21 missense mutations might be predicted by those features, the scoring system might be valuable for clinical diagnosis.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Estudos Retrospectivos , Fumar , Tomografia Computadorizada por Raios X/métodosRESUMO
Gastric cancer (GC) poses a significant health challenge worldwide, necessitating the identification of predictive biomarkers to improve prognosis. Dysregulated lipid metabolism is a well-recognized hallmark of tumorigenesis, prompting investigation into apolipoproteins (APOs). In this study, we focused on apolipoprotein D (APOD) following comprehensive analyses of APOs in pan-cancer. Utilizing data from the TCGA-STAD and GSE62254 cohorts, we elucidated associations between APOD expression and multiple facets of GC, including prognosis, tumor microenvironment (TME), cancer biomarkers, mutations, and immunotherapy response, and identified potential anti-GC drugs. Single-cell analyses and immunohistochemical staining confirmed APOD expression in fibroblasts within the GC microenvironment. Additionally, we independently validated the prognostic significance of APOD in the ZN-GC cohort. Our comprehensive analyses revealed that high APOD expression in GC patients was notably associated with unfavorable clinical outcomes, reduced microsatellite instability and tumor mutation burden, alterations in the TME, and diminished response to immunotherapy. These findings provide valuable insights into the potential prognostic and therapeutic implications of APOD in GC.
RESUMO
BACKGROUND: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV-posDLBCL) is an aggressive B-cell lymphoma that often presents similar morphological and immune phenotype features to that of EBV-negative DLBCL (EBV-negDLBCL). AIMS AND METHODS: To better understand their difference in genomic landscape, we performed whole-exome sequencing (WES) of EBV-posDLBCL and EBV-negDLBCL. RESULTS: This analysis revealed a new mutational signature 17 (unknown) and signature 29 (smoking) in EBV-posDLBCL as well as a specific mutational signature 24 (associated with aflatoxin) in EBV-negDLBCL. Compared with EBV-negDLBCL, more somatic copy number alterations (CNAs) and deletions were detected in EBV-posDLBCL (p = 0.01). The most frequent CNAs specifically detected in EBV-posDLBCL were gains at 9p24.1 (PDL1 and JAK2), 8q22.2-q24.23 (DEPTOR and MYC), and 7q31.31-q32.2 (MET), which were validated in additional EBV-posDLBCL cases. Overall, 53.7% (22/41) and 62.9% (22/35) of the cases expressed PD-L1 and c-MET, respectively, in neoplastic cells, whereas only 15.4% (4/26) expressed c-MYC. Neoplastic c-MET expression was positively correlated with PD-L1 (p < 0.001) and MYC expression (p = 0.016). However, EBV-posDLBCL cases did not show any differences in overall survival between PD-L1-, c-MET-, or c-MYC-positive and -negative cases or between age-related groups. Analysis of the association between somatic mutation load and EBV status showed no difference in the distribution of tumor mutant burden between the two lymphomas (p = 0.41). Recurrent mutations in EBV-posDLBCL implicated several genes, including DCAF8L1, KLF2, and NOL9, while in EBV-negDLBCL, ANK2, BPTF, and CNIH3 were more frequently mutated. Additionally, PIM1 is the most altered gene in all the WES-detected cases. CONCLUSIONS: Our results confirm that genomic alteration differs significantly between EBV-posDLBCL and EBV-negDLBCL, and reveal new genetic alterations in EBV-posDLBCL. The positive correlation of c-MET and PD-L1/c-Myc expression may be involved in the pathogenesis of EBV-posDLBCL, which is should be explored prospectively in trials involving MET-directed therapies.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Humanos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Genômica , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Background: The purpose of this study is to present a series of primary intracranial sarcomas (PIS), a rare type of tumor of the central nervous system, in order to improve our understanding of the disease. These tumors are heterogeneous and prone to recurrence after resection, exhibiting a high mortality rate. As PIS has yet to be understood and studied on a large scale, it is vital for further evaluation and research. Methods: Our study included 14 cases of PIS. The patients' clinical, pathological, and imaging features were retrospectively analyzed. Additionally, targeted DNA next-generation sequencing (NGS) was applied for the 481-gene panel to detect gene mutations. Results: The average age for PIS patients was 31.4 years. Headache (7, 50.0%) was the most common symptom leading to the hospital visit. Twelve cases had PIS located in the supratentorial area and two in the cerebellopontine angle region. The maximum tumor diameter ranged from 19.0 mm to 130.0 mm, with an average diameter of 50.3 mm. Pathological types of tumors were heterogeneous, with chondrosarcoma being the most common, followed by fibrosarcoma. Eight of the 10 PIS cases that underwent MRI scanning showed gadolinium enhancement; 7 of these cases were heterogeneous, and 1 of them was garland-like. Targeted sequencing was performed in two cases and identified mutations in genes such as NRAS, PIK3CA, BAP1, KDR, BLM, PBRM1, TOP2A, DUSP2, and CNV deletions of SMARCB1. Additionally, the SH3BP5::RAF1 fusion gene was also detected. Of the 14 patients, 9 underwent a gross total resection (GTR), and 5 chose subtotal resection. Patients who underwent GTR displayed a trend toward superior survival. Among the 11 patients with available follow-up information, one had developed lung metastases, three had died, and eight were alive. Conclusion: PIS is extremely rare compared to extracranial soft sarcomas. The most common histological type of intracranial sarcoma (IS) is chondrosarcoma. Patients who underwent GTR of these lesions showed improved survival rates. Recent advancements in NGS aided in the identification of diagnostic and therapeutic PIS-relevant targets.
RESUMO
BACKGROUND: Lower-grade gliomas (LGG) are heterogeneous diseases by clinical, histological, and molecular criteria. We aimed to personalize the diagnosis and therapy of LGG patients by developing and validating robust cellular morphometric subtypes (CMS) and to uncover the molecular signatures underlying these subtypes. METHODS: Cellular morphometric biomarkers (CMBs) were identified with artificial intelligence technique from TCGA-LGG cohort. Consensus clustering was used to define CMS. Survival analysis was performed to assess the clinical impact of CMBs and CMS. A nomogram was constructed to predict 3- and 5-year overall survival (OS) of LGG patients. Tumor mutational burden (TMB) and immune cell infiltration between subtypes were analyzed using the Mann-Whitney U test. The double-blinded validation for important immunotherapy-related biomarkers was executed using immunohistochemistry (IHC). RESULTS: We developed a machine learning (ML) pipeline to extract CMBs from whole-slide images of tissue histology; identifying and externally validating robust CMS of LGGs in multicenter cohorts. The subtypes had independent predicted OS across all three independent cohorts. In the TCGA-LGG cohort, patients within the poor-prognosis subtype responded poorly to primary and follow-up therapies. LGGs within the poor-prognosis subtype were characterized by high mutational burden, high frequencies of copy number alterations, and high levels of tumor-infiltrating lymphocytes and immune checkpoint genes. Higher levels of PD-1/PD-L1/CTLA-4 were confirmed by IHC staining. In addition, the subtypes learned from LGG demonstrate translational impact on glioblastoma (GBM). CONCLUSIONS: We developed and validated a framework (CMS-ML) for CMS discovery in LGG associated with specific molecular alterations, immune microenvironment, prognosis, and treatment response.
Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/patologia , Inteligência Artificial , Relevância Clínica , Glioma/patologia , Aprendizado de Máquina , Microambiente TumoralRESUMO
CONTEXT.: The pathology residency program began in China in 2014. There has been no competency assessment on training programs in the Hubei province of China. OBJECTIVE.: To evaluate the current residency training curriculum and resident performance in Hubei Province. DESIGN.: A 37-question online questionnaire was designed to cover general demographic information, diagnostic competency, expectations of ideal caseload for gross and preview, teaching patterns, examinations, research activities, weak points, and other topics in pathology practice. RESULTS.: A total of 166 participants, including 62 postgraduate year (PGY) 2, 49 PGY3, and 55 new practicing pathologists, responded to the survey. PGY3 residents were found to be more competent than PGY2 in diagnostic competency. Forty-five of 55 new practicing pathologists (81.8%) reported that they could sign out cases independently, whereas 10 of 55 (18.2%) were found to still need transitional time for learning before working independently. Some residents could sign out cytopathology cases and gained knowledge in immunohistochemistry and histochemical staining, while some residents did not receive adequate training in molecular pathology. The ideal caseloads for gross and preview during residency were greater than 5000 and 7000, respectively. Nonneoplastic diseases, neuropathology, dermatopathology, hematopathology, and soft tissue pathology were considered difficult subspecialties in pathology practice. CONCLUSIONS.: While residents trained in Hubei Province have met the basic requirements for qualified pathologists, more efforts need to be made in many areas, such as a well-structured training curriculum and better-designed proficiency examinations. The findings of this study are of great importance to prioritizing training in the future.
Assuntos
Internato e Residência , Humanos , Currículo , Educação de Pós-Graduação em Medicina/métodos , Avaliação Educacional/métodos , Competência Clínica , ChinaRESUMO
Background: Lung cancer histologic types and subtypes are closely associated with treatment selection and prognosis prediction. In this study, we aim to evaluate the suitability of computed tomography-guided percutaneous core needle biopsy (CT-guided PCNB) in typing and subtyping lung cancer. Methods: From August 2007 to December 2015, the patients who underwent CT-guided PCNB and lung lesion resection were retrospectively collected and analyzed. All pathological sections were reassessed in consensus by 2 junior pathologists (group A) and 2 senior pathologists (group B), respectively. All cases were diagnosed on 3 levels: first, malignant and benign diagnosis; second, histologic types diagnosis; and third, histologic subtypes diagnosis and compared with surgery results. Pearson chi-square test was used to compare the differences of diagnostic accuracy between pathologists in group A and group B. Results: A cohort of 160 patients was included in this study. On the first level, the diagnostic accuracy was 90.63% (group A) and 94.38% (group B), (P = .20). On the second level, the diagnostic accuracy for malignant lesions, adenocarcinoma (ADC), and squamous cell carcinoma (SQC) were, respectively, 72.66%, 84.72%, and 69.05% (group A) and 76.98%, 90.28%, and 71.43% (group B) (P > .05). On the third level, the diagnostic accuracy for ADC subtypes were 26.39% (group A) and 55.56% (group B) (P < 0.01); for SQC subtypes were 28.57% (group A) and 38.10% (group B) (P = 0.36). Conclusion: Small specimens obtained by CT-guided PCNB were suitable for the diagnosis of lung cancer histologic types, which may contribute to the selection of a suitable treatment strategy for the unresectable lung cancers. While for the diagnosis of subtypes, discussion with experienced pathologists was recommended.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/patologia , Biópsia com Agulha de Grande Calibre , Humanos , Biópsia Guiada por Imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Current treatments for lower-grade glioma (LGG) do not effectively improve life expectancy rates, and this is a major global health concern. Improving our knowledge of this disease will ultimately help to improve prevention, accurate prognosis, and treatment strategies. Pyroptosis is an inflammatory form of regulated cell death, which plays an important role in tumor progression and occurrence. There is still a lack of effective markers to evaluate the prognosis of LGG patients. We collected paraffin-embedded tissue samples and prognostic information from 85 patients with low-grade gliomas and fabricated them into a tissue microarray. Combining data from public databases, we explored the relationship between pyroptosis-related genes (PRGs) and the prognoses of patients with LGG and investigated their correlations with the tumor microenvironment (TME) by means of machine learning, single-cell, immunohistochemical, nomogram, GSEA, and Cox regression analyses. We developed a six-gene PRG-based prognostic model, and the results have identified CASP4 as an effective marker for LGG prognosis predictions. Furthermore, the effects on immune cell infiltration may also provide guidance for future immunotherapy strategies.
Assuntos
Glioma , Piroptose , Humanos , Piroptose/genética , Bases de Dados Factuais , Glioma/genética , Imunoterapia , Conhecimento , Microambiente TumoralRESUMO
RATIONALE AND OBJECTIVES: To develop and validate a nomogram for differentiating second primary lung cancers (SPLCs) from pulmonary metastases (PMs). MATERIALS AND METHODS: A total of 261 lesions from 253 eligible patients were included in this study. Among them, 195 lesions (87 SPLCs and 108 PMs) were used in the training cohort to establish the diagnostic model. Twenty-one clinical or imaging features were used to derive the model. Sixty-six lesions (32 SPLCs and 34 PMs) were included in the validation set. RESULTS: After analysis, age, lesion distribution, type of lesion, air bronchogram, contour, spiculation, and vessel convergence sign were considered to be significant variables for distinguishing SPLCs from PMs. Subsequently, these variables were selected to establish a nomogram. The model showed good distinction in the training set (area under the curve = 0.97) and the validation set (area under the curve = 0.92). CONCLUSION: This study found that the nomogram calculated from clinical and radiological characteristics could accurately classify SPLCs and PMs.
Assuntos
Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Nomogramas , Tórax/patologia , Tomografia Computadorizada por Raios X/métodosRESUMO
Purpose We aimed to determine the epidermal growth factor receptor (EGFR) genetic profile of lung cancer in Asians, and develop and validate a non-invasive prediction scoring system for EGFR mutation before treatment. Methods This was a single-center retrospective cohort study using data of patients with lung cancer who underwent EGFR detection (n = 1450) from December 2014 to October 2020. Independent predictors were filtered using univariate and multivariate logistic regression analyses. According to the weight of each factor, a prediction scoring system for EGFR mutation was constructed. The model was internally validated using bootstrapping techniques and temporally validated using prospectively collected data (n = 210) between November 2020 and June 2021.Results In 1450 patients with lung cancer, 723 single mutations and 51 compound mutations were observed in EGFR. Thirty-nine cases had two or more synchronous gene mutations. We developed a scoring system according to the independent clinical predictors and stratified patients into risk groups according to their scores: low-risk (score <4), moderate-risk (score 4-8), and high-risk (score >8) groups. The C-statistics of the scoring system model was 0.754 (95% CI 0.729-0.778). The factors in the validation group were introduced into the prediction model to test the predictive power of the model. The results showed that the C-statistics was 0.710 (95% CI 0.638-0.782). The Hosmer-Lemeshow goodness-of-fit showed that χ2 = 6.733, P = 0.566. Conclusions The scoring system constructed in our study may be a non-invasive tool to initially predict the EGFR mutation status for those who are not available for gene detection in clinical practice.
Assuntos
Neoplasias Pulmonares , Povo Asiático/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Estudos RetrospectivosRESUMO
BACKGROUND: The corona virus disease 2019 (COVID-19) has been a pandemic for more than one year and estimated to affect the whole world in the near future. CASE SUMMARY: Here we reported that one COVID-19 patient with vesicles was treated by bullectomy. The patient's perioperative laboratory tests were analyzed. The pathological findings of bullectomy were described and compared with those of common bulla cases. CONCLUSION: This patient with vesicles underwent bullectomy and had a poor prognosis. He showed diffuse alveolar damage and extensive necrosis in bullectomy specimen. We hope our report will be of interest for clinicians who will treat COVID-19 patients in the future.
RESUMO
AIMS: High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta-2 microglobulin (B2M) in lower-grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration. METHODS: A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan-Meier survival analysis and meta-analysis were used for survival analysis. GO(Gene-ontology) enrichment analysis, co-expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma. RESULTS: We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta-analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co-expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines. CONCLUSIONS: We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration.
Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/metabolismo , Microambiente Tumoral/fisiologia , Microglobulina beta-2/biossíntese , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Estudos de Coortes , Bases de Dados Genéticas/tendências , Glioma/genética , Glioma/mortalidade , Humanos , Taxa de Sobrevida/tendências , Microglobulina beta-2/genéticaRESUMO
AIMS: Secondary gliosarcoma (SGS) rarely arises post treatment of primary glioblastoma multiforme (GBM), and contains gliomatous and sarcomatous components. The origin and clonal evolution of SGS sarcomatous components remain uncharacterized. Therapeutic radiation is mutagenic and can induce sarcomas in patients with other tumor phenotypes, but possible causal relationships between radiotherapy and induction of SGS sarcomatous components remain unexplored. Herein, we investigated the clonal origin of SGS in a patient with primary GBM progressing into SGS post-radiochemotherapy. METHODS: Somatic mutation profile in GBM and SGS was examined using whole-genome sequencing and deep-whole-exome sequencing. Mutation signatures were characterized to investigate relationships between radiochemotherapy and SGS pathogenesis. RESULTS: A mutation cluster containing two founding mutations in tumor-suppressor genes NF1 (variant allele frequency [VAF]: 50.0% in GBM and 51.1% in SGS) and TP53 (VAF: 26.7% in GBM and 50.8% in SGS) was shared in GBM and SGS. SGS exhibited an overpresented C>A (G>T) transversion (oxidative DNA damage signature) but no signature 11 mutations (alkylating-agents - exposure signature). Since radiation induces DNA lesions by generating reactive oxygen species, the mutations observed in this case of SGS were likely the result of radiotherapy rather than chemotherapy. CONCLUSIONS: Secondary gliosarcoma components likely have a monoclonal origin, and the clone possessing mutations in NF1 and TP53 was likely the founding clone in this case of SGS.
Assuntos
Neoplasias Encefálicas , Evolução Clonal/genética , Glioblastoma , Gliossarcoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Gliossarcoma/genética , Gliossarcoma/secundário , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Reverse Variant of Follicular Lymphoma (RVFL) is one of the rare morphological variants of FL, characterized by dark staining small centrocytes in the center and pale staining large centroblasts at the periphery of the neoplastic follicles. Only rare cases of RVFL have been described to date. The histological appearance of this little known variant of FL may be misinterpreted if pathologists are unaware of its existence. The main purpose of this study is to draw pathologists' attention to such an uncommon growth pattern of FL so that this variant can be correctly recognized and the clinical significance further studied in the future. METHODS: Four cases of FL with unusual morphologic features were evaluated for the expression pattern of CD20, CD10, BCL6, BCL2, CD21, CD23, CD3, CD5, Cyclin D1, IgD and Ki67 by immunohistochemistry. Fluorescence in situ hybridization (FISH) with break-apart probes was performed to detect BCL2 gene rearrangement. RESULTS: All four cases showed distinctive morphologic pattern of RVFL; in addition, each also exemplified unique morphological features. Immunohistochemical stains confirmed the cells in both the central areas and the peripheral cuffs had the same immunophenotypic profiles, contrasting to the FL with marginal zone differentiation in which only the center of the nodules showed expression of CD10. FISH demonstrated BCL2 gene rearrangement in all cases. CONCLUSION: The growth pattern of this rare FL variant may mimic FL with marginal-zone differentiation and other entities including but not limited to marginal zone lymphoma (MZL), progressive transformation of germinal centers (PTGC) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Pathologists should be familiar with this unusual morphological variant to avoid diagnostic pitfalls.