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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.
J Pathol Transl Med ; 2021 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-34353008

RESUMEN

Background: Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters. Materials and Methods: Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed. Results: Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006). Conclusion: Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

4.
J Epidemiol ; 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33536377

RESUMEN

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

5.
J Gynecol Oncol ; 31(6): e78, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33078588

RESUMEN

OBJECTIVE: Kallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining. METHODS: We analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0-1+) (n=120 patients) and moderate/strong (2-3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors. RESULTS: Patients with KLK5 2-3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0-1+. With a median follow-up of 60.8 (interquartile range, 47.5-77.9) months, patients with KLK5 2-3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0-1+ group) and 59.4% (vs. 72.8% in the KLK5 0-1+ group), respectively (all p<0.05). KLK5 2-3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis. CONCLUSIONS: KLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.

6.
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
7.
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
8.
Diagnostics (Basel) ; 10(8)2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32824242

RESUMEN

We investigated the clinicopathological characteristics of 31 cases of pleomorphic high-grade squamous intraepithelial lesions (PHSIL) of the uterine cervix. We reviewed electronic medical records and all available slides to collect clinical and pathological information. PHSILs were histologically characterized by significant nuclear enlargement, marked pleomorphism, hyperchromasia, increased mitotic activity, and frequent atypical mitoses. In the majority of cases (24/31; 77.4%), this striking nuclear atypia involved both the surface epithelium and the endocervical glands. In the remaining seven cases, pleomorphic cells were observed in the surface epithelium only. PHSILs involving both the surface epithelium and glands showed higher mitotic counts and Ki-67 labelling indices than the surface-only PHSILs. Invasive squamous cell carcinoma was present in only one case (3.2%), and none developed recurrent disease. Our observations of striking nuclear atypia in cases of HSIL did not indicate increased aggressiveness. Further investigations are required for confirmation of our data in larger cohorts.

9.
Anticancer Res ; 40(3): 1487-1494, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32132048

RESUMEN

BACKGROUND/AIM: The clinicopathological and prognostic significances of programmed death ligand 1 (PD-L1) expression in triple-negative breast carcinoma (TNBC) are still unclear. We investigated whether PD-L1 expression is associated with clinicopathological characteristics and outcomes of TNBC patients. MATERIALS AND METHODS: We performed immunostaining for PD-L1 (SP142) in 83 TNBCs. Staining proportion of ≥1% was regarded as positive PD-L1 expression. RESULTS: Positive intratumoral (IT) PD-L1 expression (19/83; 22.9%) was inversely associated with lymphovascular invasion (LVI) and distant metastasis, and was significantly associated with better disease-free survival for TNBC patients. Positive stromal PD-L1 expression (44/83; 53.0%) also correlated inversely with LVI. CONCLUSION: Positive IT PD-L1 expression was associated with favorable outcomes in TNBC. In addition, positive IT and stromal PD-L1 were inversely associated with LVI and distant metastasis of TNBC.


Asunto(s)
Antígeno B7-H1/biosíntesis , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Antígeno B7-H1/inmunología , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , República de Corea
10.
Diagnostics (Basel) ; 10(3)2020 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-32164210

RESUMEN

Malignancies of extragenital origin very rarely metastasize to the uterine body. Endometrium-limited metastases may pose diagnostic challenges in endometrial curettage specimens as they may be misdiagnosed as primary endometrial tumors. We investigated the clinicopathological characteristics of seven cases with endometrial-limited metastases from carcinomas of the nasopharynx (n = 1), breast (n = 2), colon (n = 2), stomach (n = 1), and appendix (n = 1). The patients' ages ranged from 36 to 71 (mean: 55.4) years. None of the patients had a remarkable gynecological history, and the presenting sign in all cases was abnormal uterine bleeding. Although myometrial involvement was absent, multiple metastases were already present in extrauterine locations such as the lung, liver, bone, abdominopelvic peritoneum, and omentum. All patients underwent ultrasonographic examination prior to endometrial curettage. The histologies of the endometrial metastases identified from the curettage specimens were identical to those of the corresponding primary tumors. Ancillary tests including immunostaining and Epstein-Barr virus-encoded RNA in situ hybridization confirmed the extragenital origin. Endometrium-limited metastases from extragenital malignancies are extremely rare. They present with abnormal vaginal bleeding and mimic endometrial carcinomas of endometrioid or poorly differentiated types. Since their clinical presentations and histological features are similar to those of primary endometrial tumors, pathologists should consider the possibility of metastases while evaluating endometrial curettage specimens obtained from patients with a history of extragenital malignancies.

11.
Mol Clin Oncol ; 12(2): 117-119, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31929881

RESUMEN

The current study reports the case of multifocal ectopic thyroid tissues in the breast. Ectopic thyroid tissue is an uncommon entity found not only in the cysts of thyroglossal ducts, but also along the thyroglossal duct. The most frequent location of this tissue is the base of the tongue, but they can also occur in the anterior tongue, submandibular or sublingual region, larynx, trachea, mediastinum and heart. Only a single case of ectopic thyroid tissue in breast has been previously reported in English literature. However, the current case was associated with abnormal embryological development compared with previous reports, which are attributed to abnormal implantation.

12.
Cell Death Differ ; 27(4): 1341-1354, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31527799

RESUMEN

Notch, an essential factor in tissue development and homoeostasis, has been reported to play an oncogenic function in a variety of cancers. Here, we report ubiquitin-specific protease 8 (USP8) as a novel deubiquitylase of Notch1 intracellular domain (NICD). USP8 specifically stabilizes and deubiquitylates NICD through a direct interaction. The inhibition of USP8 downregulated the Notch signalling pathway via NICD destabilization, resulting in the retardation of cellular growth, wound closure, and colony forming ability of breast cancer cell lines. These phenomena were restored by the reconstitution of NICD or USP8, supporting the direct interaction between these two proteins. The expression levels of NICD and USP8 proteins were positively correlated in patients with advanced breast cancer. Taken together, our results suggest that USP8 functions as a positive regulator of Notch signalling, offering a therapeutic target for breast cancer.

13.
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
14.
Anticancer Res ; 39(10): 5361-5367, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31570430

RESUMEN

BACKGROUND/AIM: The mechanism responsible for B-cell translocation gene 1 (BTG1) down-regulation in breast carcinoma remains unknown. We examined the BTG1 expression status in breast carcinoma cells and investigated the mechanism underlying the observed alterations. MATERIALS AND METHODS: Four breast carcinoma cell lines (SK-BR-3, MDA-MB-231, T-47D, and MCF-7), and one normal mammary epithelial cell line (MCF-10A) were analyzed. BTG1 expression was examined using quantitative reverse transcription polymerase chain reaction (PCR) and western blot. Methylation status of the BTG1 promoter was analyzed using methylation-specific PCR (MSP). To investigate the effect of methylation on BTG1, the cells were treated with a demethylating agent. RESULTS: The carcinoma cells expressed significantly lower levels of BTG1 mRNA and protein than normal cells. The BTG1 promoter was highly methylated in the carcinoma cells. 5-aza-2-deoxycytidine significantly restored BTG1 expression. CONCLUSION: Down-regulation of BTG1 expression through epigenetic repression is involved in mammary carcinogenesis. BTG1 is a potential diagnostic marker and therapeutic target for breast carcinoma.


Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN/genética , Regulación hacia Abajo/genética , Proteínas de Neoplasias/genética , Regiones Promotoras Genéticas/genética , Carcinogénesis/genética , Línea Celular Tumoral , Epigénesis Genética/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Células MCF-7 , ARN Mensajero/genética
15.
In Vivo ; 33(5): 1485-1492, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31471396

RESUMEN

BACKGROUND/AIM: We aimed to demonstrate the use of next-generation sequencing (NGS) to confirm the presence of tumor protein 53 (TP53) mutations in tubo-ovarian and peritoneal high-grade serous carcinoma (HGSC) with a wild-type p53 immunostaining pattern and investigate whether the TP53 mutational status is altered by chemotherapy. MATERIALS AND METHODS: A commercial NGS panel comprising 171 genes was used to analyze the genetic profiles of 15 HGSC samples. Paired specimens obtained before and after chemotherapy were available for four patients. RESULTS: All examined samples exhibited TP53 mutations. For all the patients who underwent neoadjuvant or postoperative adjuvant chemotherapy, TP53 mutations identified in samples obtained after chemotherapy were the same as those detected in pre-chemotherapeutic samples. CONCLUSION: HGSCs exhibit TP53 mutations even though a subset of HGSCs displayed a wild-type p53 immunostaining pattern. Chemotherapy does not affect the TP53 mutational status in HGSC.


Asunto(s)
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Neoplasias de las Trompas Uterinas/genética , Neoplasias de las Trompas Uterinas/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Proteína p53 Supresora de Tumor/genética , Anciano , Biomarcadores de Tumor , Neoplasias de las Trompas Uterinas/metabolismo , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Estadificación de Neoplasias , Proteína p53 Supresora de Tumor/metabolismo
16.
Oral Oncol ; 96: 34-41, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31422211

RESUMEN

OBJECTIVES: Signaling between cancer stem cells (CSC) and their extracellular matrix has a crucial role in CSC progression and maintenance. However, mediators of this signaling pathway in head and neck squamous cell carcinoma (HNSCC) are largely unknown. Here, we explored whether integrin ß1, which is one of the key regulators of the communication between cells and their microenvironment, affected the stemness of HNSCC cells. MATERIALS AND METHODS: We examined self-renewal capacity, chemoresistance, and xenograft tumorigenicity after knockdown of integrin ß1 in primary HNSCC cells. In addition, we studied the role of focal adhesion kinase (FAK), an intracellular downstream molecule of integrin signaling, in influencing stemness of HNSCC. The relevance of Notch1 and integrin ß1 interactions in HNSCC cells was also examined. Finally, immunohistochemical analysis was carried out to test whether the coexpression of integrin ß1 and Notch1 in the samples from HNSCC patients correlated with their survival. RESULTS: Targeting integrin ß1 in HNSCC cells inhibited self-renewal, chemoresistance, and in vivo tumor-forming capacity. Treatment with an inhibitor of FAK decreased self-renewal capacities and expression of various putative stem cell markers (Oct4, Sox2, and Nanog) in a dose-dependent manner. Moreover, knockdown of integrin ß1 decreased the expression of Notch1 and its target genes (Hey1 and Hes1). Notably, HNSCC patients demonstrating simultaneous expression of integrin ß1 and Notch1 in their tissue samples had significantly worse survival rate. CONCLUSION: Integrin ß1/Notch1 axis has a significant role in the regulation of stemness in HNSCC.


Asunto(s)
Biomarcadores/metabolismo , Integrina beta1/metabolismo , Células Madre Neoplásicas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Desnudos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Pathol Res Pract ; 215(5): 1071-1075, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30846412

RESUMEN

BACKGROUND: With the recent development of molecular tests for various biomarkers, it has become even more important to prepare adequate tissue samples. However, little is known about how the effect of cold ischemia time or formalin fixation time can affect KRAS mutation detection in colorectal cancer. METHODS: This study included the results of KRAS mutation tests for colorectal cancer in 401 specimens. We investigated clinicopathologic factors that may affect DNA quality of formalin-fixed, paraffin-embedded (FFPE) tissue including specimen type, cold ischemia time, and formalin fixation time and assessed the detection rate of the KRAS mutation in samples with varying DNA quality. RESULTS: Sample DNA quality for KRAS mutation test was better in biopsy specimens, which showed markedly shorter cold ischemia time and shorter formalin fixation time compared to resection specimens. A cold ischemia time of one hour or less was associated with better sample DNA quality. But the formalin fixation time was not a significant factor when it fell within the range performed in routine pathology diagnosis. When prolonged formalin fixation was tested, we confirmed that the specimen DNA quality gradually got worse from one month to three months. CONCLUSIONS: The biopsy specimens showed better sample DNA quality for KRAS mutation test compared to resection specimens. In a routine diagnostic pathology setting, the cold ischemia time was an important factor affecting DNA quality and the formalin fixation had a wide time range for optimal DNA quality.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/genética , Análisis Mutacional de ADN/métodos , Proteínas Proto-Oncogénicas p21(ras)/análisis , Manejo de Especímenes/métodos , Biomarcadores de Tumor/genética , Isquemia Fría , Humanos , Adhesión en Parafina , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Fijación del Tejido
18.
Anticancer Res ; 39(2): 663-670, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30711943

RESUMEN

BACKGROUND/AIM: Sphingosine kinase 1 (SPHK1) is up-regulated in many different cancers and plays a crucial role in tumor development and progression. However, the prognostic value of SPHK1 in colorectal cancer (CRC) remains unclear. MATERIALS AND METHODS: The expression of SPHK1 in CRC cell lines and 328 CRC tissue samples was examined. It was also investigated whether SPHK1 expression is associated with clinicopathological characteristics and outcomes in patients with CRC. RESULTS: HCT 116 and HT-29 cells expressed significantly higher SPHK1 levels than did CCD 841 CoTr. On immunohistochemistry, SPHK1 expression was significantly higher in CRC tissue than in normal colonic mucosal tissue, with 34.1% of CRC patients exhibiting high SPHK1 expression. High SPHK1 expression in CRC was significantly associated with higher histological grade, deeper invasion depth, lymphatic invasion, vascular invasion, and development of distant metastasis, and was shown to be an independent predictor of distant metastasis. Furthermore, patients with high SPHK1 expression had significantly lower overall survival rates than those with low expression. CONCLUSION: High SPHK1 expression was significantly associated with aggressive CRC behavior and worse overall survival, and was an independent predictor of distant metastasis. SPHK1 may thus be a potential prognostic biomarker and therapeutic target in CRC patients.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Metástasis de la Neoplasia , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Células HCT116 , Células HT29 , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Resultado del Tratamiento
19.
BMC Gastroenterol ; 19(1): 24, 2019 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-30736729

RESUMEN

BACKGROUND: Although the incidence of early gastric cancer (EGC) continues to rise, there have been few studies on the intra-gastric distribution and locational characteristics of EGCs. In addition, there has been no attempt to visualize the intra-gastric distribution of EGCs using a merged tumor map. METHODS: We investigated the anatomic distribution of 644 cases of EGCs and analyzed the correlation between clinicopathologic findings and location by dividing areas of the stomach vertically and transversely. Merged tumor maps were generated using 310 surgically resected cases. RESULTS: Early gastric cancer was most commonly located in the antrum (57.5%) along the lesser curvature (37.8%). The intra-gastric distributions were similar in the merged tumor maps. Vertically, cancers of the middle third were associated with younger patient age, larger tumor size, and more frequent poorly differentiated (PD) or signet ring cell histology than cancers in other sites. Submucosal invasion was most frequently observed in the upper third. When divided transversely, tumors in the anterior or posterior wall showed more frequent PD or signet ring cell histology than those along the lesser or greater curvatures. CONCLUSIONS: EGC is the most prevalent in the antrum along the lesser curvature and has characteristic locational features, including histologic type, invasion depth, patient age, and tumor size. These results will improve the endoscopic detection rate of EGC and help to determine endoscopic resectability.


Asunto(s)
Neoplasias Gástricas/patología , Estómago/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/cirugía , Resección Endoscópica de la Mucosa , Femenino , Gastrectomía , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Estómago/cirugía , Neoplasias Gástricas/cirugía , Carga Tumoral
20.
BMC Cancer ; 18(1): 938, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30285668

RESUMEN

BACKGROUND: Carcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer. METHODS: Invasive ductal breast cancer patients (N = 145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures. RESULTS: CD8 + TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73-12.31) was associated with poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR p for trend = 0.063). CONCLUSIONS: A relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.


Asunto(s)
Neoplasias de la Mama/patología , Linfocitos Infiltrantes de Tumor/inmunología , Adulto , Anciano , Análisis de Varianza , Neoplasias de la Mama/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Estimación de Kaplan-Meier , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Neutrófilos/inmunología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos
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