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1.
Anticancer Res ; 41(9): 4609-4617, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475089

RESUMEN

BACKGROUND/AIM: This study aimed to assess the yield of an Oncomine comprehensive assay v3 (OCAv3)-based next-generation sequencing (NGS) analysis for detecting anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) fusions in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: NGS data from 85 NSCLC cases were reviewed. ALK and ROS1 fusion status was compared to conventional tests. RESULTS: ALK or ROS1 fusion reads were detected in 17 NSCLC cases. Results in 10 NSCLC cases showed concordance with conventional tests, high-count fusion reads, a lack of mutually exclusive mutations of ALK or ROS1, and frequent signet-ring cell component. Seven NSCLC cases showing discordant results exhibited low to intermediate fusion read counts and mutations mutually exclusive from ALK or ROS1. CONCLUSION: Cases showing high-count fusion reads in OCAv3-based NGS have a strong possibility of carrying ALK or ROS1 fusion. Cases with low- to intermediate-count fusion reads should be interpreted with caution and may require additional confirmative tests.


Asunto(s)
Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Análisis de Secuencia de ARN/métodos , Adulto , Anciano , Anciano de 80 o más Años , Análisis Citogenético , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
2.
Medicina (Kaunas) ; 57(8)2021 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-34441043

RESUMEN

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015-2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542-10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Femenino , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Pronóstico , Transducción de Señal , Neoplasias de la Mama Triple Negativas/genética
3.
Anticancer Res ; 41(5): 2719-2726, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33952503

RESUMEN

BACKGROUND/AIM: We present a case of uterine dedifferentiated mesonephric-like adenocarcinoma (MLA). CASE REPORT: A 54-year-old woman underwent total hysterectomy for a uterine mass under the impression of a uterine sarcoma. Histologically, MLA exhibited various growth patterns including tubular and glandular architecture. Undifferentiated carcinoma (UC) displayed discohesive tumor cells without any obvious architecture. Immunohistochemically, UC was positive for epithelial markers in very few scattered tumor cells. MLA exhibited the wild-type p53 expression pattern, whereas UC showed a uniform and strong p53 immunoreactivity. Targeted sequencing analysis revealed an identical Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in both components. A pathogenic missense tumor protein 53 (TP53) mutation was detected in UC, but not in MLA. CONCLUSION: The mutant p53 expression pattern exclusively detected in UC was concordant with the presence of missense TP53 mutation. Our observations suggested that TP53 mutation is associated with the possible transformation from MLA to UC.


Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma/diagnóstico , Sarcoma/diagnóstico , Enfermedades Uterinas/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Carcinoma/genética , Carcinoma/patología , Carcinoma/cirugía , Desdiferenciación Celular/genética , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Sarcoma/genética , Sarcoma/patología , Sarcoma/cirugía , Enfermedades Uterinas/patología , Enfermedades Uterinas/cirugía , Conductos Mesonéfricos/diagnóstico por imagen , Conductos Mesonéfricos/patología , Conductos Mesonéfricos/cirugía
4.
In Vivo ; 35(2): 921-927, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33622884

RESUMEN

BACKGROUND/AIM: The application of Oncomine Comprehensive Assay v3 (OCAv3) panel in diffuse gliomas (DGs) remains unknown. We investigated the utility of OCAv3-based next-generation sequencing (NGS) in isocitrate dehydrogenase (IDH)-mutated grade II-III DGs. PATIENTS AND METHODS: We collected 20 tissue samples obtained from IDH-mutated grade II-III DG patients and performed OCAv3-based NGS. RESULTS: By conventional molecular methods, the 20 DGs were classified into seven astrocytomas and 13 oligodendrogliomas. OCAv3 detected all mutations identified in these samples using the conventional methods. The results were highly corroborated by the known mutations in each group. Clustered copy number loss of genes located at the 1p and 19q loci was detected in all 13 oligodendroglioma cases, which harbor the 1p/19q codeletion. CONCLUSION: The application of OCAv3-based NGS will improve diagnostic accuracy in DG, with the most beneficial aspects expected in detecting copy number alterations to identify the 1p/19q codeletion correctly.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Astrocitoma/diagnóstico , Astrocitoma/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Cromosomas Humanos Par 1/genética , Humanos , Isocitrato Deshidrogenasa/genética , Mutación , Oligodendroglioma/diagnóstico , Oligodendroglioma/genética
5.
Neurooncol Adv ; 2(1): vdaa129, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33305267

RESUMEN

Background: The incidence and clinical features of the malignant transformation of benign meningiomas are poorly understood. This study examined the risk of the malignant transformation of benign meningiomas after surgery or stereotactic radiosurgery. Methods: We systematically reviewed studies published between 1979 and 2019 using PubMed, Scopus, and other sources. We analyzed pooled data according to the PRISMA guideline to clarify the incidence rate of malignant transformation (IMT) and factors affecting malignant transformation in surgically or radiosurgically treated benign meningiomas. Results: IMT was 2.98/1000 patient-years (95% confidence interval [CI] = 1.9-4.3) in 13 studies in a single-arm meta-analysis. Although the evidence level of the included studies was low, the heterogeneity of the incidence was mostly explained by the tumor location. In meta-regression analysis, skull base tumors had a significantly lower IMT than non-skull base tumors, but no gender association was observed. IMT after radiosurgery in 9 studies was 0.50/1000 person-years (95% CI = 0.02-1.38). However, a higher proportion of skull base tumors, lower proportion of males, and lower salvage surgery rate were observed in the radiosurgery group than in the surgery group. The median time to malignant change was 5 years (interquartile range = 2.5-8.2), and the median survival after malignant transformation was 4.7 years (95% CI = 3.7-8) in individual case data. Conclusion: IMT of benign meningioma was significantly affected by the tumor location. Radiosurgery did not appear to increase IMT, but exact comparisons were difficult because of differences in study populations.

6.
In Vivo ; 34(6): 3619-3626, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33144476

RESUMEN

BACKGROUND/AIM: Histone modification is associated with tumorigenesis and cancer progression. Recent studies have revealed the prognostic value of histone modification; however, its prognostic role in distal bile duct cancer remains unclear. PATIENTS AND METHODS: We analyzed the expression of H3K9me3, H4K20me3, and H3K36me3 and its correlation with survival outcomes in resected samples from 88 patients with distal bile duct cancer. RESULTS: Low expression rates of H3K9me3, H4K20me3, and H3K36me3 were significantly associated with poor overall survival (p=0.003, 0.008, and 0.047, respectively) and event-free survival (p=0.03 for H3K9m3). Additionally, low-expression of H3K9me3 was an independent poor prognostic indicator (p<0.001; HR=7.85; 95% CI=2.693-22.883). CONCLUSION: H3K9me3 was an independent poor prognostic factor in distal common bile duct cancer. Our results suggest that histone markers are potential prognostic markers and provide better management for patients at risk for an aggressive course of disease.


Asunto(s)
Neoplasias de los Conductos Biliares , Histonas , Neoplasias de los Conductos Biliares/genética , Conducto Colédoco , Histonas/genética , Histonas/metabolismo , Humanos , Pronóstico , Procesamiento Proteico-Postraduccional
7.
Cancer Genomics Proteomics ; 17(6): 813-826, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33099482

RESUMEN

BACKGROUND/AIM: Mesonephric carcinoma (MNC) is a rare but notable entity of the female genital tract. While many researchers have acknowledged and studied MNC, much remains unknown on the characteristics of mesonephric remnant (MNR) or hyperplasia (MNH). There has not been any study examining the molecular features of MNR and MNH so far. The aim of this study was to investigate the clinicopathological and molecular characteristics of ten uterine mesonephric lesions, including two MNRs without atypia, four MNHs without atypia, and three MNHs with atypia. MATERIALS AND METHODS: We reviewed the electronic medical records and all available slides of ten cases from multiple institutions. Targeted sequencing and array comparative genomic hybridization were performed. RESULTS: Three atypical MNHs displayed nuclear enlargement, mild-to-moderate nuclear pleomorphism, and nuclear membrane irregularity, and harbored pathogenic Kirsten rat sarcoma 2 viral oncogene homolograt sarcoma 2 viral oncogene homolog (KRAS) mutation. Two of those that co-existed with MNC harbored the same sequence alterations as each of their adjacent MNC. One of the three atypical MNHs harbored chromosome 1q gain. CONCLUSION: Atypical MNH is a potential premalignant lesion in which KRAS mutation and chromosome 1q gain play an important role in the early stage of mesonephric carcinogenesis.


Asunto(s)
Cromosomas Humanos Par 1/genética , Mutación con Ganancia de Función , Hiperplasia/patología , Mesonefroma/patología , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Femenino , Humanos , Hiperplasia/genética , Mesonefroma/genética , Persona de Mediana Edad , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Pronóstico , Neoplasias del Cuello Uterino/genética
8.
Anticancer Res ; 40(10): 5777-5785, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32988905

RESUMEN

BACKGROUND/AIM: Emerging evidence suggests that Insulin-like growth factor II mRNA-binding protein 3 (IMP3) promotes tumor progression in several human malignancies. We investigated whether IMP3 expression has clinicopathological and prognostic significance in gallbladder adenocarcinoma (GBAC). PATIENTS AND METHODS: We examined immunohistochemical IMP3 expression in 204 GBACs and its associations with clinicopathological parameters and patient outcomes. RESULTS: The majority (87.7%) of GBACs exhibited at least focal cytoplasmic and membranous IMP3 immunoreactivity. Tumor-specific IMP3 expression highlighted proper muscle invasion, which was not detected in the corresponding hematoxylin and eosin-stained slides. This finding upgraded pathological tumor stage (pT) from pT1a to pT1b in four well-differentiated GBACs. High IMP3 expression was associated with high histological grade, advanced stage, and lymphatic invasion, as well as worse overall survival. CONCLUSION: Tumor-specific IMP3 expression in GBAC is helpful in determining the tumor extent, especially in well-differentiated tumors. High IMP3 expression reflects aggressive oncogenic behavior of GBAC. IMP3 expression may be used as a diagnostic and prognostic marker in GBAC.


Asunto(s)
Carcinoma/genética , Neoplasias de la Vesícula Biliar/genética , Pronóstico , Proteínas de Unión al ARN , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Carcinoma/patología , Femenino , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Proteínas de Unión al ARN/genética
9.
Anticancer Res ; 40(10): 5925-5932, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32988924

RESUMEN

BACKGROUND/AIM: Paired box 8 (PAX8) is an organ-specific marker discriminating Müllerian and breast carcinomas. Recent studies have described PAX8 expression in a small subset of breast carcinomas, which may cause a diagnostic pitfall in the determination of cancer origin. The aim of this study was to investigate characteristics of PAX8-expressing metastatic breast carcinomas (MBCs) to help elucidate the primary site of occurrence. PATIENTS AND METHODS: Using immunohistochemistry, we examined PAX8 status in 80 MBCs and 52 matched primary breast carcinomas (PBCs). RESULTS: A total of 20% of MBCs displayed PAX8 expression and the concordance rate of PAX8 expression between MBCs and PBCs was 92.3%. In MBCs, PAX8 expression was significantly associated with high-grade features (p=0.042), estrogen and progesterone receptor negativities (p=0.005 and p=0.017, respectively). CONCLUSION: PAX8 may be identified in MBCs with high-grade and non-luminal molecular subtypes. Careful assessment is needed when designating a primary site relying principally on PAX8 positivity.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Inmunohistoquímica , Factor de Transcripción PAX8/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Persona de Mediana Edad
10.
Brain Tumor Pathol ; 37(4): 136-144, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32761533

RESUMEN

Oncogenic gene fusions have been reported in diffuse gliomas and may serve as potential therapeutic targets. Here, using next-generation sequencing analysis (Illumina TruSight Tumor 170 panel), we analyzed a total of 356 diffuse gliomas collected from 2017 to 2019 to evaluate clinical, pathological, and genetic features of gene fusion. We found 53 cases of glioblastomas harboring the following oncogenic gene fusions: MET (n = 18), EGFR (n = 14), FGFR (n = 12), NTRK (n = 5), RET (n = 2), AKT3 (n = 1), and PDGFRA fusions (n = 1). Gene fusions were consistently observed in both IDH-wildtype and IDH-mutant glioblastomas (8.8% and 9.4%, p = 1.000). PTPRZ1-MET fusion was the only fusion that genetically resembled secondary glioblastomas (i.e., high frequency of IDH mutation, ATRX loss, TP53 mutation, and absence of EGFR amplification), whereas other gene fusion types were similar to primary glioblastomas (i.e., high frequency of IDH-wildtype, TERT mutation, EGFR amplification, and PTEN mutation). In IDH-wildtype glioblastoma patients, multivariable analysis revealed that the PTPRZ1-MET fusion was associated with poor progression-free survival (HR [95% CI]: 5.42 (1.72-17.05), p = 0.004). Additionally, we described two novel cases of CCDC6-RET fusion in glioma. Collectively, our findings indicate that targetable gene fusions are associated with aggressive biological behavior and can aid the clinical treatment strategy for glioma patients.


Asunto(s)
Neoplasias Encefálicas/genética , Fusión Génica/genética , Estudios de Asociación Genética , Glioblastoma/genética , Glioma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/genética , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Proteínas del Citoesqueleto/genética , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Glioma/mortalidad , Glioma/patología , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas c-ret/genética , Tasa de Supervivencia
11.
J Nippon Med Sch ; 87(3): 157-161, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32655092

RESUMEN

Screening esophagogastroduodenoscopy of a 65-year-old man revealed a 4.7-cm polypoid in the gastric high body. Clinical and laboratory findings, including serum gastrin level (460 pg/mL) and biopsy findings, were consistent with a diagnosis of type I neuroendocrine tumor (NET). Histologically, the mass consisted of dilated tortuous glands at the surface and grade 1 NET in deeper tissue. Some hyperplastic glands exhibited a transition to adenocarcinoma, which invaded the NET, simulating a "tumor in tumor" appearance. Next-generation sequencing revealed that the adenocarcinoma component harbored a TP53 mutation, whereas the NET component showed no pathogenic mutation. To our knowledge, this unusual collision of adenocarcinoma and NET within a single gastric hyperplastic polyp has not been previously described. This case suggests that large gastric hyperplastic polyps should be carefully examined because of the possibility of underlying NET and malignant transformation of surface epithelium.


Asunto(s)
Adenocarcinoma/patología , Pólipos Intestinales/patología , Neoplasias Primarias Múltiples/patología , Tumores Neuroendocrinos/patología , Neoplasias Gástricas/patología , Anciano , Transformación Celular Neoplásica/patología , Humanos , Masculino
12.
Mod Pathol ; 33(4): 541-550, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31822803

RESUMEN

Secretory carcinoma is a salivary gland tumor with a characteristic chromosomal translocation that results in an ETV6-NTRK3 fusion gene. Secretory carcinoma shows relatively frequent rates of lymph-node metastasis and tumor recurrence and has a characteristic histology. Except for the ETV6 translocation, genomic alterations in secretory carcinoma have not been reported. In the present study, we characterized the novel recurrent genetic mutations of secretory carcinoma. On the basis of histology, immunohistochemistry, and ETV6 gene break-apart fluorescence in situ hybridization assays, 22 tumors were classified as secretory carcinomas (19 ETV6 translocation-positive and 3 ETV6 translocation-negative secretory carcinomas) and their clinicopathologic characteristics were reviewed. Targeted deep sequencing analyses were performed on 20 secretory carcinomas (17 ETV6 translocation-positive and 3 ETV6 translocation-negative secretory carcinomas) to investigate their genetic alterations. The A16V (C→T) mutation in PRSS1, which encodes a cationic trypsinogen and has a mutation associated with hereditary pancreatitis and pancreatic adenocarcinoma, was observed in 40% (8/20) (7/17 of ETV6 translocation-positive and 1/3 of ETV6 translocation-negative secretory carcinomas). Pathogenic variants of MLH1, MUTYH, and STK11 were also identified. Variants of uncertain significance included mutations in KMT5A. These novel characteristic genetic alterations may advance current understandings of secretory carcinoma tumorigenesis and progression, leading to improved diagnoses and treatment strategies.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Mutación , Neoplasias de las Glándulas Salivales/genética , Adolescente , Adulto , Anciano , Carcinoma/patología , Niño , ADN Glicosilasas/genética , Femenino , Predisposición Genética a la Enfermedad , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Neoplasias de las Glándulas Salivales/patología , Translocación Genética , Tripsina/genética , Adulto Joven
13.
J Nippon Med Sch ; 87(6): 350-354, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33431761

RESUMEN

Early gastric cancer (EGC) with synchronous distant metastasis is extremely rare. Here, we report a case of stage IV Epstein-Barr virus (EBV) -associated EGC. A 51-year-old man presented with vague abdominal pain of 3 weeks' duration. Imaging studies revealed enlargement of the left supraclavicular, perigastric, and para-aortic lymph nodes, a huge gastric polypoid mass, and multiple liver masses. Histopathological examination of a biopsy specimen of the supraclavicular lymph node showed poorly differentiated carcinoma expressing EBV in tumor cell nuclei. The gastric mass exhibited tubular adenocarcinoma, which also expressed EBV in tumor cell nuclei. After 3 weeks of palliative chemotherapy with fluoropyrimidine and platinum, the patient died of liver failure. Next-generation sequencing analysis revealed mutation of the CDKN1B gene in the metastatic carcinoma and mutations of the CTNNB1 and PIK3R1 genes in the gastric carcinoma. In addition to the rare presentation of EBV-associated EGC, this case showed marked morphological and molecular differences between primary and metastatic tumors, which suggests clonal evolution of EBV-associated GC.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/virología , Herpesvirus Humano 4/aislamiento & purificación , Mutación , Neoplasias Primarias Múltiples , Neoplasias Gástricas/genética , Neoplasias Gástricas/virología , Adenocarcinoma/patología , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Resultado Fatal , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Paliativos , Neoplasias Gástricas/patología , beta Catenina/genética
14.
Sci Rep ; 9(1): 15628, 2019 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-31666552

RESUMEN

The fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT). We investigated whether P-I-R (progressive vs. indeterminate vs. regressive) staging is predictive of hepatocellular carcinoma (HCC) recurrence in patients with chronic hepatitis B (CHB) taking AVT who underwent resection. Patients with CHB-related HCC who underwent curative resection between 2004 and 2017 and had received ≥2 years AVT at the time of resection were eligible. Two pathologists performed P-I-R staging. In total, 104 patients with CHB-related HCC were enrolled. The mean age of the study population was 56.3 years. The mean duration of AVT at the time of resection was 62.6 months. During the follow-up period (mean, 45.5 months), 20 (19.2%) and 14 (13.5%) patients developed early and late recurrence of HCC, respectively. The cumulative incidence of late recurrence was significantly lower in patients with regressive patterns than in those with indeterminate and progressive patterns according to P-I-R staging (P = 0.015, log-rank test), although the cumulative incidence of overall recurrence according to P-I-R staging was similar. Hepatitis B virus DNA levels (hazard ratio [HR] = 3.200, P = 0.020) and the regressive P-I-R staging pattern (HR = 0.127, P = 0.047) independently predicted the risk of late recurrence. One-time assessment of the P-I-R staging at the time of curative resection in patients with CHB-related HCC receiving AVT independently predicted late HCC recurrence. Therefore, qualitative fibrosis assessment by P-I-R staging might be useful in predicting the outcomes of patients with CHB undergoing AVT.


Asunto(s)
Antivirales/administración & dosificación , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Cirrosis Hepática/patología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Humanos , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad
15.
Anticancer Res ; 39(11): 6299-6305, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31704860

RESUMEN

BACKGROUND/AIM: A minority of grade I meningiomas (MG1s) recur after surgical resection and their progression is associated with high grade transformation (HGT). This study aimed to characterize the clinicoradiological features of recurrent MGs (RMG) with HGT. PATIENTS AND METHODS: We identified 17 patients diagnosed with MG1 who then underwent surgery for RMG. Patients were categorized into HGT group vs. non-HGT (nHGT) group based on RMG histological grade and clinicoradiological features were comparatively analyzed. RESULTS: HGT was observed in 41.4% of RMGs. Original tumor size was larger in the HGT group and recurrence time interval was shorter. Following recurrence, 57.1% in the HGT group experienced further disease progression, compared to 22.2% in the nHGT group. CONCLUSION: A considerable HGT rate in RMGs developed after MG1 was observed. Although HGT was not distinguished from nHGT by radiological features, HGT in RMG was associated with larger initial tumor size and shorter recurrence time interval.


Asunto(s)
Transformación Celular Neoplásica/patología , Neoplasias Meníngeas/patología , Meningioma/patología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
16.
Anticancer Res ; 39(9): 4947-4955, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519600

RESUMEN

BACKGROUND/AIM: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) plays an important role in the adhesion, invasion, and metastasis of tumor cells. Although emerging evidence suggests that IMP3 promotes tumor progression in several malignancies, the expression of IMP3 and its prognostic implication in adenocarcinoma of the ampulla of Vater (AVAC) has not been clarified to date. MATERIALS AND METHODS: The IMP3 expression status in 87 AVAC tissues was examined using immunostaining, and its association with various clinicopathological features and outcome of patients with AVAC was investigated. RESULTS: The vast majority (87.4%) of AVAC cases displayed at least focal cytoplasmic and membranous IMP3 immunoreactivity in tumor cells, whereas IMP3 expression was consistently absent from normal biliary epithelial cells. Tumor-specific IMP3 expression was associated with submucosal and pancreatic invasion, which were not identified in the corresponding hematoxylin and eosin-stained slides. This finding led to up-staging of the pathological tumor stage in two cases of well-differentiated AVAC. In addition, high IMP3 expression was significantly associated with a poorly differentiated histology (p=0.026). Survival analyses revealed that high IMP3 expression independently predicted shorter recurrence-free (p=0.003) and overall (p=0.029) survival. CONCLUSION: Our study demonstrated tumor-specific IMP3 expression in AVAC, which will be helpful in determining invasion depth and tumor extent in patients with well-differentiated tumors, as well as indicating worse survival of patients with AVAC. Our data highlight IMP3 expression status as a potential diagnostic and prognostic marker for AVAC.


Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/genética , Neoplasias del Conducto Colédoco/mortalidad , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias del Conducto Colédoco/diagnóstico , Neoplasias del Conducto Colédoco/metabolismo , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Proteínas de Unión al ARN/genética , Carga Tumoral
17.
Yonsei Med J ; 60(10): 914-923, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31538426

RESUMEN

PURPOSE: Few efforts have been made to integrate a next generation sequencing (NGS) panel into standard clinical treatment of ovarian cancer. The aim of this study was to investigate the clinical utility of NGS and to identify clinically impactful information beyond targetable alterations. MATERIALS AND METHODS: We conducted a retrospective review of 84 patients with ovarian cancer who underwent NGS between March 1, 2017, and July 31, 2018, at the Yonsei Cancer Hospital. We extracted DNA from formalin-fixed, paraffin-embedded tissue samples of ovarian cancer. The TruSight Tumor 170 gene panel was used to prepare libraries, and the MiSeq instrument was used for NGS. RESULTS: Of the 84 patients, 55 (65.1%) had high-grade serous carcinomas. Seventy-three (86.7%) patients underwent NGS at the time of diagnosis, and 11 (13.3%) underwent NGS upon relapse. The most common genetic alterations were in TP53 (64%), PIK3CA (15%), and BRCA1/2 (13%), arising as single nucleotide variants and indels. MYC amplification (27%) was the most common copy number variation and fusion. Fifty-seven (67.9%) patients had more than one actionable alteration other than TP53. Seven (8.3%) cases received matched-target therapy based on the following sequencing results: BRCA1 or 2 mutation, poly ADP ribose polymerase inhibitor (n=5); PIK3CA mutation, AKT inhibitor (n=1); and MLH1 mutation, PD-1 inhibitor (n=1). Fifty-three (63.0%) patients had a possibility of treatment change, and 8 (9.5%) patients received genetic counseling. CONCLUSION: Implementation of NGS may help in identifying patients who might benefit from targeted treatment therapies and genetic counseling.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Ováricas/genética , Pautas de la Práctica en Medicina , Adulto , Anciano , Variaciones en el Número de Copia de ADN/genética , Femenino , Genoma Humano , Humanos , Persona de Mediana Edad , Terapia Molecular Dirigida , Mutación/genética , Neoplasias Ováricas/patología , Estudios Retrospectivos
18.
J Neurooncol ; 142(3): 445-454, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30710203

RESUMEN

PURPOSE: The TruSight Tumor 170 (TST-170) panel consists of a DNA workflow for the identification of single-nucleotide variants, small insertions and deletions, and copy number variation, as well as a panel of 55 genes for a RNA workflow for the identification of splice variants and gene fusions. To date, the application of TST-170 in diffuse gliomas (DGs) has not been described. METHODS: We analyzed 135 samples of DG, which were diagnosed by WHO criteria based on histological features and conventional molecular tests including immunostaining, 1p/19q FISH, and analysis of MGMT methylation and TERT promoter mutation. RESULTS: A total of 135 cases consisted of 38 IDH-mutant [17 astrocytoma (AC), 13 oligodendroglioma (OD) and eight glioblastoma (GBM)], 87 IDH-wildtype (six AC, three OD and 78 GBM), and 10 diffuse midline glioma, H3K27M-mutant. DNA analysis enabled the detection of all mutations identified in these samples by conventional techniques, and the results were highly comparable to the known mutations in each subtype. RNA analysis detected four fusion genes including PTPRZ1-MET, FGFR3-TACC3, FAM131B-BRAF, and RET-CCDC6 and one splicing variant (EGFR vIII mutant). Clustered copy number loss in 1p and 19q loci genes were detected in 1p/19q-codeleted OD. CONCLUSIONS: The application of TST-170 panel based NGS in clinical and laboratory setting is expected to improve diagnostic accuracy and prognostication. Most benefits are expected in IDH-wildtype DG, a group of genetically heterogenous tumors harboring DNA sequence changes, copy number alterations, and fusions in a large number of oncogenes and tumor suppressor genes.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Variaciones en el Número de Copia de ADN , Glioma/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Femenino , Estudios de Seguimiento , Glioma/patología , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Adulto Joven
19.
Am J Surg Pathol ; 43(1): 12-25, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29189288

RESUMEN

Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract mainly occurring in the uterine cervix. To date, only a few cases of MNAC arising from of the uterine body (UB-MNAC) have been reported. The clinicopathologic and molecular characteristics of UB-MNAC remain unknown. In this study, we investigated the clinical, histopathologic, immunohistochemical, and genetic features of UB-MNAC. In total, 11 cases were included. Six patients developed metastatic disease, most commonly in lungs (5/6). Histopathologically, UB-MNAC was characterized by an admixture of tubular, glandular, papillary, retiform, glomeruloid, sex cord-like, and comedonecrosis-like architectural patterns. Three adverse pathologic characteristics, including advanced International Federation of Gynecology and Obstetrics stage, high mitotic activity, and presence of lymphovascular the invasion, were independent factors predicting the development of metastasis. All cases were positive for GATA-binding protein 3 and paired box 2 expression and showed wild-type p53, patchy p16, and preserved PTEN expression, as indicated by immunohistochemistry. Next-generation sequencing using 12 samples (11 primary tumors and 1 metastatic tumor) revealed 42 single nucleotide variations in 16 genes, mostly in KRAS (10/12) and ARID1A (9/12). Copy number variation was found in 16 genomic regions, and consisted of 57 gains and 10 losses, with 1q gain (11/12) being the most prevalent. In conclusion, UB-MNAC displays an aggressive biological behavior, with a tendency to metastasize to the lungs. Adverse pathologic characteristics reflect the aggressive nature of UB-MNAC. Distinct molecular features of UB-MNAC include frequent somatic mutations of KRAS and ARID1A and gain of 1q.


Asunto(s)
Adenocarcinoma/patología , Mesonefroma/patología , Neoplasias Uterinas/patología , Adenocarcinoma/genética , Anciano , Femenino , Humanos , Mesonefroma/genética , Persona de Mediana Edad , Neoplasias Uterinas/genética
20.
Virchows Arch ; 473(2): 165-175, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29926183

RESUMEN

Causes of peritoneal carcinomatosis (PC) in patients with a history of breast carcinoma include both metastatic breast carcinoma (MBC) and primary peritoneal/ovarian carcinoma (PPOC). The origin of PC is important to determine the appropriate treatment strategy. Cytological examination of the peritoneal fluid (PF), which may be the first diagnostic approach to PC, is of distinct value in confirming the presence of malignant cells and determining the origin of PC. We analyzed the clinicopathological and cytomorphological characteristics of 33 patients with a history of breast carcinoma whose PF cytology contained malignant cells. Cases showing positive immunoreactivity for PAX8 and a lack of GATA3 expression were considered as PPOC. Sixteen patients developed PC caused by PPOC. PPOC patients were characterized by early-stage primary breast carcinoma, absence of non-peritoneal MBC before PC, and normal serum levels of CEA and CA15-3. Fourteen PPOC patients had pathogenic germline BRCA mutations. Cytological examination revealed that most of the PPOC cases had a dominant papillary arrangement of the tumor cells with severe nuclear pleomorphism, occasional bizarre nuclei, and atypical mitotic figures. Patients with PPOC who underwent cytoreductive surgery had a significantly longer survival time compared to those who did not, or MBC patients. In patients with a history of breast carcinoma presenting with PC, the presence of early-stage primary breast carcinoma, no prior non-peritoneal MBC, and a dominant papillary cellular arrangement pattern in the PF cytology were independent predictors of PPOC. Cytoreductive surgery significantly improved survival for patients with PPOC.


Asunto(s)
Líquido Ascítico/patología , Neoplasias de la Mama/patología , Carcinoma/patología , Neoplasias Primarias Secundarias/patología , Neoplasias Ováricas/patología , Neoplasias Peritoneales/secundario , Adulto , Líquido Ascítico/química , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/química , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Antígeno Carcinoembrionario/sangre , Carcinoma/química , Carcinoma/genética , Carcinoma/secundario , Procedimientos Quirúrgicos de Citorreducción , Diagnóstico Diferencial , Femenino , Factor de Transcripción GATA3/análisis , Mutación de Línea Germinal , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mucina-1/sangre , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/química , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/cirugía , Neoplasias Ováricas/química , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Factor de Transcripción PAX8/análisis , Neoplasias Peritoneales/química , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/cirugía , Valor Predictivo de las Pruebas , Resultado del Tratamiento
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