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1.
Tumour Biol ; 42(1): 1010428319901052, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31959092

RESUMEN

Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast cancer (negative to estrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2). Recent gene expression studies of triple-negative breast cancers have highlighted their heterogeneity and the importance of immune responses in their biology and prognostic assessment. Indeed, regulatory T cells may play a crucial role in producing an immune-suppressed microenvironment, notably in triple-negative breast cancers. Feline invasive mammary carcinomas arise spontaneously in immune-competent animals, in which we hypothesized that the immune tumor microenvironment also plays a role. The aims of this study were to determine the quantity and prognostic value of forkhead box protein P3-positive peritumoral and intratumoral regulatory T cells in feline invasive mammary carcinomas, and to identify an immune-suppressed subgroup of triple-negative basal-like feline invasive mammary carcinomas. One hundred and eighty female cats with feline invasive mammary carcinomas, treated by surgery only, with 2-year follow-up post-mastectomy, were included in this study. Forkhead box protein P3, estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor type 2, and cytokeratin 14 expression were assessed by automated immunohistochemistry. Peritumoral regulatory T cells were over 300 times more abundant than intratumoral regulatory T cells in feline invasive mammary carcinomas. Peritumoral and intratumoral regulatory T cells were associated with shorter disease-free interval and overall survival in both triple-negative (ER-, PR-, HER2-, N = 123 out of 180) and luminal (ER+ and/or PR+, N = 57) feline invasive mammary carcinomas. In feline triple-negative basal-like (CK14+) mammary carcinomas, a regulatory T-cell-enriched subgroup was associated with significantly poorer disease-free interval, overall survival, and cancer-specific survival than regulatory T-cell-poor triple-negative basal-like feline invasive mammary carcinomas. High regulatory T-cell numbers had strong and negative prognostic value in feline invasive mammary carcinomas, especially in the triple-negative basal-like subgroup, which might contain a "basal-like immune-suppressed" subtype, as described in triple-negative breast cancer. Cats with feline invasive mammary carcinomas may thus be interesting spontaneous animal models to investigate new strategies of cancer immunotherapy in an immune-suppressed tumor microenvironment.


Asunto(s)
Neoplasias Mamarias Animales/patología , Neoplasias de la Mama Triple Negativas/patología , Animales , Gatos , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Inmunosupresión/métodos , Neoplasias Mamarias Animales/metabolismo , Pronóstico , Receptores Estrogénicos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Microambiente Tumoral/fisiología
2.
Acta Cytol ; 64(1-2): 92-102, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30909279

RESUMEN

Salivary gland tumor aspiration cytology is a useful preoperative test to guide the most appropriate clinical and surgical management for these patients. Although salivary gland cytology is often useful to distinguish between non-neoplastic lesions, benign neoplasms and malignant neoplasms, there remain many challenges in this area. Specifically, these tumors are uncommon and may have considerable morphologic overlap, especially in the setting of a malignant tumor. This article reviews some of the immunohistochemical and molecular characteristics of more common salivary gland neoplasms that pathologists and cytotechnologists may encounter. When used in combination with morphologic features, such ancillary testing can be useful to further refine the differential diagnosis, more strongly favor a particular entity, or in some instances confidently provide a specific diagnosis.


Asunto(s)
Biopsia con Aguja Fina/métodos , Citodiagnóstico/métodos , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Diagnóstico Diferencial , Humanos , Inmunohistoquímica/métodos , Técnicas de Diagnóstico Molecular/métodos , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/genética , Glándulas Salivales/metabolismo
3.
Acta Cytol ; 64(1-2): 16-29, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30878997

RESUMEN

Pulmonary cytology is a challenging diagnostic tool, and it is usually evaluated considering medical history and radiological findings in order to reach an accurate diagnosis. Since the majority of lung cancer patients have an advanced stage at diagnosis, a cytological specimen is frequently the only material available for diagnosis and further prognostic/predictive marker determination. Several types of specimens can be obtained from the respiratory system (including sputum, bronchoalveolar lavage, bronchial brushing, fine needle aspiration, and pleural fluid) with different technical preclinical management protocols and different diagnostic yields. Immunocytochemistry (ICC) has a pivotal role in the determination of diagnostic, prognostic, and predictive markers. Therefore, limited cytology samples are to be used with a cell-sparing approach, to allow both diagnostic ICC evaluation as well as predictive marker assessment by ICC or specific molecular assays. In this review, we describe the most common ICC markers used for the diagnosis and prognostic/predictive characterization of thoracic tumors in different cytological specimens.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Citodiagnóstico/métodos , Inmunohistoquímica/métodos , Neoplasias Pulmonares/metabolismo , Pulmón/metabolismo , Biopsia con Aguja Fina/métodos , Lavado Broncoalveolar/métodos , Broncoscopía/métodos , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Esputo/metabolismo
4.
Acta Cytol ; 64(1-2): 81-91, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30889574

RESUMEN

Fine needle aspiration samples and small biopsies provide a minimally invasive diagnostic modality for mass lesions. When an infectious process is suspected based on initial evaluation, ancillary techniques can assist in making a specific diagnosis. Here we review the cytopathology that should prompt additional testing and review the availability and interpretation of special stains, immunohistochemistry, and in situ hybridization. In addition, this review addresses when special cultures may be necessary and the use of newer molecular techniques for pathogen identification.


Asunto(s)
Biopsia con Aguja Fina/métodos , Citodiagnóstico/métodos , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Bacterias/genética , Bacterias/aislamiento & purificación , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Humanos , Técnicas de Diagnóstico Molecular/métodos , Guías de Práctica Clínica como Asunto
5.
Acta Cytol ; 64(1-2): 124-135, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31509835

RESUMEN

Pancreatic cysts are increasingly detected on imaging studies. Accurate determination of the cyst type is important to provide appropriate care for the patients. It is also very clear that not one single modality can provide adequate diagnostic information. A multidisciplinary approach is the key to the diagnosis of pancreatic cysts. In this setting, the role of ancillary testing, which includes biochemical testing (carcinoembryonic antigen and amylase levels in the cyst), molecular testing (e.g., KRAS, GNAS, VHL, and CTNB1), and/or immunohistochemical tests are very important to obtain an accurate diagnosis. This review will discuss helpful ancillary tests in common pancreatic cyst neoplasms and how to approach the diagnosis of pancreatic cysts.


Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Quiste Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Antígeno Carcinoembrionario/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Análisis Mutacional de ADN/métodos , Humanos , Inmunohistoquímica/métodos , Mutación , Quiste Pancreático/genética , Quiste Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética
6.
Acta Cytol ; 64(1-2): 175-181, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31121596

RESUMEN

Biliary brushing cytology has become the standard of practice for the investigation of strictures of the biliary and pancreatic duct systems. The methodology however has a limitation in that it has low diagnostic sensitivity when only cytologic evaluation is used. A number of testing methodologies have been applied to brushing specimens in an attempt to improve overall sensitivity without loss of specificity. These have included DNA ploidy analysis, immunocytochemistry, individual gene mutational analysis, fluorescence in-situ hybridization (FISH), and next generation sequencing (NGS). Currently, FISH coupled with routine cytology appears to be the method of choice for improving diagnostic sensitivity. NGS shows significant promise for improvement of diagnostic sensitivity.


Asunto(s)
Neoplasias de los Conductos Biliares/diagnóstico , Conductos Biliares Intrahepáticos/patología , Sistema Biliar/patología , Colangiocarcinoma/diagnóstico , Citodiagnóstico/métodos , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Sistema Biliar/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Sensibilidad y Especificidad
7.
Acta Cytol ; 64(1-2): 30-39, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30783052

RESUMEN

Human papilloma virus (HPV)-related squamous cell carcinoma (SCC) is biologically unique and has a better prognosis than conventional SCC of the head and neck. p16 immunohistochemistry emerged as a valuable surrogate marker for HPV in oropharyngeal SCC. The criteria for a positive p16 result in tissue specimens are well established. However, there is no consensus regarding interpreting p16 staining in cell blocks and other cytology specimens. This review discusses the current evidence on p16 testing in cytology specimens and also highlights other methods for HPV testing, including DNA and RNA in situ hybridization, as well as other molecular HPV tests.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Inmunohistoquímica/métodos , Infecciones por Papillomavirus/metabolismo , Biopsia con Aguja Fina/métodos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Humanos , Hibridación in Situ/métodos , Papillomaviridae/genética , Papillomaviridae/fisiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Sensibilidad y Especificidad
8.
Chemosphere ; 238: 124581, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31445333

RESUMEN

Lead (Pb) pollution is one of the most serious environmental problems and has attracted worldwide attention. Pb causes hematological, central nervous system, as well as renal toxicity, and so on. Although many investigations about Pb in blood to evaluate pollution status and toxic effects have been reported, there are open question about biological behavior of Pb. In order to reveal any toxicological mechanisms or influences, we focused on the local distribution of Pb in mice organs. Lead acetate (100 mg/L and 1000 mg/L) in drinking water were given to the BALB/c mice (male, seven weeks of age, N = 24) for three weeks. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis revealed a homogenous distribution of Pb in the liver and inhomogeneous distribution in the kidney and brain. The hippocampus, thalamus, and hypothalamus had higher concentrations than other areas such as the white matter. Surprisingly, in the kidney, Pb tended to accumulate in the medulla rather than the cortex, strongly suggesting that high sensitivity areas and high accumulation areas differ. Moreover, distribution of stromal interacting protein 1 (STIM1) which is candidate gene of Pb pathway to the cells was homogenous in the liver and kidney whereas inhomogeneous in the brain. In contrast to our hypothesis, interestingly, Pb exposure under the current condition did not induce mRNA expressions for any candidate channel or transporter genes. Thus, further study should be conducted to elucidate the local distribution of Pb and other toxic metals, and pathway that Pb takes to the cells.


Asunto(s)
Química Encefálica/efectos de los fármacos , Riñón/química , Plomo/análisis , Hígado/química , Molécula de Interacción Estromal 1/análisis , Animales , Encéfalo/metabolismo , Inmunohistoquímica/métodos , Terapia por Láser , Masculino , Espectrometría de Masas/métodos , Ratones , Ratones Endogámicos BALB C , Análisis Espectral
9.
Virchows Arch ; 475(6): 771-779, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31686194

RESUMEN

The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)-associated markers stathmin and LLT-1 were positive in most of the cases (12/13 and 12/13, respectively). Interestingly, FOXP-1 was uniformly positive in PTFL (12/13 cases) in contrast to reactive GCs in FH, where only a few isolated positive cells were observed. FISH revealed no evidence of BCL2, BCL6, or MYC rearrangements in the examined cases. By PCR, clonal immunoglobulin gene rearrangements were detected in 100% of the tested PTFL cases. Our study confirmed the unique morphological and immunophenotypic features of PTFL and suggests that FOXP-1 can represent a novel useful diagnostic marker in the differential diagnosis between PTFL and FH.


Asunto(s)
Factores de Transcripción Forkhead/metabolismo , Linfoma de Células B/patología , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Proteínas Represoras/metabolismo , Adolescente , Adulto , Niño , Diagnóstico Diferencial , Humanos , Inmunohistoquímica/métodos , Inmunofenotipificación/métodos , Linfoma de Células B/diagnóstico , Linfoma de Células B/metabolismo , Linfoma Folicular/diagnóstico , Masculino , Estatmina/metabolismo , Adulto Joven
10.
Georgian Med News ; (294): 123-128, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31687963

RESUMEN

Microenvironment plays central role in the development of cervical precancerous and cancerous lesions. Cervical intraepithelial neoplasia (CIN) represents a group of precancerous lesions, divided into three degrees. We investigated the distribution of intraepithelial lymphocytes and macrophages in different grades of CIN. We analysed lymphocyte marker CD103, macrophage marker CD68 and proliferation marker Ki67 using standard immunohistochemistry. In addition, we investigated the distribution of lymphocytes using standard haematoxylin and eosin method. The results of our study indicated thatgrade I CIN which subsequently progressed into grade II CIN was characterised with low lymphocytic infiltration, low lympho-epithelial index and low lymphocyte proliferation index. Similar results were seen in cases of CINII which were later progressed into CINIII or in carcinoma. Therefore, we would like to recommend the analysis of microenvironment alterations in CIN lesions, in order to assess their progression potential.


Asunto(s)
Antígenos CD/metabolismo , Biomarcadores de Tumor/análisis , Transformación Celular Neoplásica/patología , Neoplasia Intraepitelial Cervical/patología , Linfocitos Intraepiteliales/patología , Antígeno Ki-67/metabolismo , Macrófagos/patología , Microambiente Tumoral , Neoplasias del Cuello Uterino/patología , Antígenos CD/análisis , Neoplasia Intraepitelial Cervical/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Antígeno Ki-67/análisis , Clasificación del Tumor , Neoplasias del Cuello Uterino/metabolismo
11.
Georgian Med News ; (294): 128-131, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31687964

RESUMEN

Histone modifications represent one of the types of epigenetic changes. Histones, undergo different types of epigenetic modifications, including the phosphorylation of serine residues. pHH3 antibodies specifically detect histon-3 protein, when phosphorylated at 10th and 28th serine residues. Traditionally pHH3 antibodies are used as proliferation marker, as it detects cells in late G2 and M phase. We studied the distribution of phosphor-histon-3 in epithelial tumors of the ovary and its relationship with ER, PR, Ki67, p53 and BCL2. Altogether, we investigated postoperative material from 160 patients. Standard immunohistochemistry was used to detect, phosphohistone-H3 (pHH3), ER, PR, Ki67, p53 and BCL2. The results of our study showed that phosphohistone-H3 expression is negatively associated with the expression of ER and PR expression, as well as with BCL2 expression, on the other hand it positively correlates with Ki67 and mutant p53 (p<0.05). In addition, the expression of phosphohistone-H3 is detected in Ki67 negative cases and its expression is increased along with the increase of malignancy grade. Our study results indicate that PHH3 might be used as an additional marker for the assessment of proliferation and malignancy potential of epithelial tumors of the ovary.


Asunto(s)
Epigénesis Genética , Histonas/análisis , Antígeno Ki-67/análisis , Índice Mitótico/métodos , Clasificación del Tumor/métodos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Fosforilación , Biomarcadores de Tumor , Proliferación Celular , Femenino , Humanos , Inmunohistoquímica/métodos
12.
Medicine (Baltimore) ; 98(44): e17782, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689847

RESUMEN

INTRODUCTION: Ovarian metastases from rectal cancer are infrequent; thus it might be hard to diagnose and treat them. Our study introduces a challenging case which highlights our method in addressing such an issue. PATIENTS CONCERNS: A 74-year-old woman was admitted to our Unit showing abdominal pain, vomit, and a gross abdominal mass located in the right iliac fossa and mesogastrium. Oncological markers recorded following abnormalities: carbohydrate antigen 19.9 (Ca19.9) = 453.40 U/mL, carbohydrate antigen 125 (Ca125) = 88.3 U/mL. DIAGNOSIS: Such a metastatic tumor being difficult to diagnose, we could not achieve a precise preoperative diagnosis. We entered the operating room with a histologic diagnosis that was highly suspicious of colon adenocarcinoma. During surgery, frozen section analysis was positive for primary ovarian cancer. Thanks to the immunohistochemistry test on the histologic specimen, which might be very helpful in diagnosing such metastatic tumor, final pathology report documented ovarian metastasis from rectal cancer. INTERVENTIONS: We performed total hysterectomy with bilateral salpingo-oophorectomy and low anterior resection of the rectum with a terminal colostomy. Adjuvant chemotherapy was administered for 6 months using FOLFOX plus panitumumab in first-line therapy. OUTCOME: At 8 months from surgery, during follow-up, a local pelvic progression of disease was detected, leading to second-line chemotherapy treatment. CONCLUSION: Correct differential diagnosis between primary and metastatic ovarian tumors is paramount in choosing the best treatment which leads to the best possible outcome. In ovarian metastatic tumors, immunohistochemistry could represent an optimal diagnostic tool.


Asunto(s)
Inmunohistoquímica/métodos , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Ováricas/diagnóstico , Neoplasias del Recto/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Primarias Múltiples/secundario , Neoplasias Ováricas/patología , Neoplasias del Recto/secundario
13.
Medicine (Baltimore) ; 98(48): e18161, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31770261

RESUMEN

RATIONALE: Epithelioid hemangioma (EH) of bone is an intermediate vascular tumor that can be locally aggressive. The optimum management of multifocal EH of bone is not well delineated. We described our experience treating one patient with multifocal EH of bone in an effort to document the effect of bisphosphonates in bone EH. PATIENT CONCERNS: In this report, a 53-year old male patient presented with back pain which was initially been diagnosed of multiple bone metastatic carcinoma by 18F-FDG PET/CT scan and bone scintigraphy. DIAGNOSIS: CT-guided bone biopsy of ilium indicated that puncture tissue had irregular hyperplasia of thick and thin-walled blood vessels, immunohistochemistry revealed positive staining for CD31 and CD34, negative for CAMTA-1, PCK and EMA, which confirmed the diagnosis of multiple EH. INTERVENTIONS: The patient was treated with 4 times of intravenous Zometa (zoledronate, 4 mg each time) with average three-month interval. Bone metabolic markers including serum bone specific alkaline phosphatase (BALP) and type I collagen cross-linked C-terminal telopeptide (CTX) levels were closely monitored before and after use of bisphosphonates each time. OUTCOME: BALP and CTX were significantly lowered following intravenous Zometa and the back pain improved with integrated therapy including bone graft fusion internal fixation surgery and vertebroplasty. CONCLUSIONS: EH of multiple bones responded favorably to intravenous Zometa with improvement of bone metabolic markers. After 1 year on follow-up, the patient was doing well with no significant pain. We suggest that bisphosphonates should be considered in the treatment of multifocal osteolytic EH of bone.


Asunto(s)
Neoplasias Óseas , Huesos , Hemangioendotelioma Epitelioide , Inmunohistoquímica/métodos , Metástasis de la Neoplasia/diagnóstico , Procedimientos Ortopédicos/métodos , Ácido Zoledrónico/administración & dosificación , Biopsia/métodos , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Remodelación Ósea/efectos de los fármacos , Huesos/diagnóstico por imagen , Huesos/metabolismo , Huesos/patología , Terapia Combinada , Diagnóstico Diferencial , Difosfonatos/administración & dosificación , Monitoreo de Drogas/métodos , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/metabolismo , Hemangioendotelioma Epitelioide/patología , Hemangioendotelioma Epitelioide/terapia , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
14.
J Cancer Res Clin Oncol ; 145(12): 2969-2982, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31612319

RESUMEN

PURPOSE: Non-canonical NFκB (NC-NFκB) pathway plays an influential role in metastasis, which promotes cancer proliferation and progression. The aim of the study was to examine the expression of NC-NFκB proteins and their correlation with clinicopathological factors associated with metastatic cases of uveal melanoma (UM) and with the patient outcome. METHOD: Expression of NC-NFκB proteins (p52, RelB, and co-expression of p52/RelB) was evaluated in 75 formalin-fixed cases of uveal melanoma by immunohistochemistry. Validation of nuclear immunoreactivity was done by western blotting. Transcriptional status of NC-NFκB genes was assessed in 60 fresh tumor tissues by quantitative real-time PCR. Co-immunoprecipitation was performed to determine the presence of native p52/RelB heterodimer in UM. Prognostic relevance was determined using Cox proportional hazard and Kaplan-Meier methods. RESULTS: Immunohistochemical expression of p52, RelB, and their co-expression was observed in 81%, 68.7%, 56.2% of metastatic cases, respectively, while their expression was seen only in 38%, 33% and 30% of non-metastatic cases. Loss of BAP-1 was correlated with expression of p52 and RelB proteins. Co-immunoprecipitation assay confirmed the putative interaction of p52 with RelB protein in metastatic cases of uveal melanoma. Co-expression of p52/RelB and expression of p52 protein was significantly correlated with decreased metastasis-free survival (MFS) (p = 0.004; p = 0.002) and overall survival (OS) (p = 0.004; p = 0.032), while the RelB expression only correlated with reduced MFS (p = 0.003). CONCLUSION: Our data showed that non-canonical NFκB proteins were significantly higher in metastatic cases and associated with poor outcome of the patients. Furthermore, the p52 protein could be used as a potential therapeutic biomarker for metastatic cases in uveal melanoma.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/genética , Melanoma/genética , Subunidad p52 de NF-kappa B/genética , Metástasis de la Neoplasia/genética , Factor de Transcripción ReIB/genética , Neoplasias de la Úvea/genética , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Melanoma/patología , Metástasis de la Neoplasia/patología , Pronóstico , Estudios Prospectivos , Transcripción Genética/genética , Neoplasias de la Úvea/patología
15.
Anticancer Res ; 39(10): 5437-5448, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31570438

RESUMEN

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) is a key multi-step process which enables cancer cells to detach from the epithelial primary tumor mass and allows them to metastasize to distant organs. We immunohistochemically analyzed the expression of the transcription factors (TWIST-1, SLUG, ZEB1, ZEB2) and components of the extracellular matrix (laminin-5, fibronectin) which influence the EMT. MATERIALS AND METHODS: Primary human breast (MDA-MB-231), colon (HT29, HCT116), ovarian (SKOV3, OVCAR3) and head and neck squamous cell carcinoma cell lines (UTSCC2, UTSCC24A) grown as xenografts were immunohistochemically analyzed in vitro and in vivo. RESULTS: A high SLUG expression was observed in every cancer entity both in vitro and in vivo. ZEB1 and ZEB2 showed a high in vivo expression especially in SKOV3 and in in vitro grown MDA-MB-231 cells. CONCLUSION: SLUG expression showed the highest expression in all cancer entities investigated. Hence, it presumably represents the master regulator of EMT in these metastatic tumor entities.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Factores de Transcripción/metabolismo , Línea Celular Tumoral , Matriz Extracelular/metabolismo , Células HCT116 , Células HT29 , Humanos , Inmunohistoquímica/métodos , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
16.
Anticancer Res ; 39(10): 5505-5513, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31570444

RESUMEN

BACKGROUND/AIM: The potential of the DNA mismatch repair (MMR) system as a prognostic predictor has been evaluated in several cancer types. However, associations between MMR and the prognostic factors of ovarian cancer are poorly understood. PATIENTS AND METHODS: MLH1 expression was evaluated by immunohistochemistry in patients with advanced serous ovarian cancer treated with platinum- and taxane-based chemotherapy. Associations between MLH1 expression and clinicopathological factors as well as claudin-4 expression were examined. RESULTS: Low MLH1 expression was significantly associated with increased progression-free and overall survival, and a normalisation of CA125 levels after chemotherapy. Additionally, low claudin-4 expression was more frequently found among the group with low MLH1 expression. CONCLUSION: Low MLH1 expression was associated with improved prognosis and is a possible predictor of the chemosensitivity of ovarian cancer. Claudin-4 might be involved in the molecular mechanisms underlying how MLH1 influences survival and chemosensitivity in patients with ovarian cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Hidrocarburos Aromáticos con Puentes/farmacología , Homólogo 1 de la Proteína MutL/metabolismo , Compuestos Organoplatinos/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Taxoides/farmacología , Anciano , Antígeno Ca-125/metabolismo , Claudina-4/metabolismo , Reparación de la Incompatibilidad de ADN/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica/métodos , Neoplasias Ováricas/patología , Pronóstico , Supervivencia sin Progresión
17.
Medicine (Baltimore) ; 98(41): e17567, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31593142

RESUMEN

RATIONALE: Pediatric-type follicular lymphoma (PTFL) is a rare neoplasm with features that differ from those of adult-type follicular lymphoma. Compared to patients with adult-type follicular lymphoma, PTFL patients often show an excellent response. Preoperative diagnosis is challenging and, therefore, an accurate diagnosis is based on the findings of postoperative pathological examination and immunohistochemistry. PATIENT CONCERNS: A 13-year-old boy presented with a slow-growing mass on the right side of his neck. DIAGNOSES: The patient was diagnosed with PTFL based on the findings of histopathological examination and immunohistochemistry. INTERVENTION: The mass was completely resected. OUTCOMES: After 12 months of postoperative follow-up, the patient achieved good recovery without recurrence. LESSONS: The optimal treatment for PTFL has not yet been defined. However, patients with PTFL always show satisfactory prognoses, regardless of treatment strategy (targeted radiotherapy, multiagent chemotherapy, or "watch and wait" strategy). Clinically, pathological and immunohistochemical analyses are necessary in the diagnoses of PTFL cases, especially for distinguishing PTFL from reactive follicular hyperplasia, to avoid unnecessary treatment.


Asunto(s)
Linfoma de Células B/patología , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Cuello/patología , Adolescente , Cuidados Posteriores , Humanos , Inmunohistoquímica/métodos , Linfoma de Células B/diagnóstico , Linfoma de Células B/inmunología , Linfoma de Células B/cirugía , Linfoma Folicular/diagnóstico , Linfoma Folicular/cirugía , Masculino , Cuello/diagnóstico por imagen , Cuello/cirugía , Resultado del Tratamiento , Ultrasonografía
18.
Mutat Res ; 816-818: 111677, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31557600

RESUMEN

LIFR functions as a tumor suppressor and metastatic suppressor of breast cancer. The present study investigates the status of LIFR gene in Indian breast cancer patients. A total of 137 breast cancer tissue and 137 adjacent normal tissue which served as controls were analyzed for mutation by automated DNA sequencing, methylation through methylation-specific polymerase chain reaction and its corresponding expression at mRNA and protein level using real-time quantitative polymerase chain reaction and immunohistochemistry respectively in Indian breast cancer patients. All the molecular findings were statistically correlated with clinopathological parameters of the patients to identify its association. LIFR mRNA expression was found to be 2.534 ±â€¯3.52 fold downregulated with subsequent absence of protein in 67.15% cases (92/137). The absence of LIFR protein coincided with 80.95% (85/105) methylated cases thereby showing a very strong correlation among the LIFR promoter methylation and LIFR protein expression (p = 0.0001). We also observed G2968C nucleotide change in 6/137 cases of exon 20 of LIFR gene resulting in Glu990Gln mutation. Correlation of LIFR promoter methylation with geographic location and age at menopause and LIFR mutation with age at menarche, age at first live birth, molecular subtypes of breast cancer, and lymph node status remained significant even after bonferroni correction (p ≤ 0.0027). All these data suggests the relevance of these associations in relation to Indian breast cancer patients. The loss of LIFR protein was frequently found in Indian breast cancer patients, and aberrant promoter methylation showed a significant correlation with its downregulation.


Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN/genética , Regulación Neoplásica de la Expresión Génica/genética , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética , Mutación/genética , Regulación hacia Abajo/genética , Femenino , Humanos , Inmunohistoquímica/métodos , India , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , ARN Mensajero/genética
19.
J Cancer Res Clin Oncol ; 145(12): 3105-3114, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31562550

RESUMEN

PURPOSE: Tumor inflammatory response was evaluated as a prognostic feature in triple-negative breast cancer (TNBC) and compared with the clinical prognosticators of breast cancer and selected biomarkers of cancer cell proliferation. METHODS: TNBC patients (n = 179) with complete clinical data and up to 18-year follow-up were obtained from Auria biobank, Turku University Hospital, Turku, Finland. Tumor-infiltrating lymphocytes (TILs) and several subtypes of inflammatory cells detected with immunohistochemistry were evaluated in different tumor compartments in full tissue sections and tissue microarrays. RESULTS: Deficiency of stromal TILs and low number of CD8+ T cells independently predicted mortality in TNBC (HR 2.4, p 0.02 and HR 2.1, p 0.02, respectively). Each 10% decrease in stromal TILs resulted in 20% increased risk of mortality. An average of 13.2-year survival difference was observed between the majority (> 75%) of patients with low (< 14% of TILs) vs high (≥ 14% of TILs) frequency of CD8+ T cells. The prognostic value of TILs and CD8+ T cells varied when evaluated in different tumor compartments. TILs and CD8+ T cells were significantly associated with Securin and Separase, essential regulators of metaphase-anaphase transition of the cell cycle. DISCUSSION: TILs and CD8+ T cells provide additional prognostic value to the established clinical prognostic markers in TNBC. However, possible clinical applications would still benefit from systematic guidelines for evaluating tumor inflammatory response. Increasing understanding on the interactions between the regulation of cancer cell proliferation and inflammatory response may in future advance treatment of TNBC.


Asunto(s)
Linfocitos T CD8-positivos/patología , Linfocitos Infiltrantes de Tumor/patología , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica/métodos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Pronóstico
20.
Medicine (Baltimore) ; 98(37): e17104, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31517842

RESUMEN

Esophageal cancer is a common human malignant tumor with high mortality. Glandular epithelial markers, such as CAM5.2, can be expressed in esophageal squamous cell carcinoma (ESCC), but the clinical significance of these cells in ESCC remains elusive.Immunohistochemical analysis of CAM5.2 was performed on 604 ESCC specimens using tissue microarray. Our study design and study population used retrospective cohorts based on the hospital information system and pathological information management system which included medical information, date of admission, procedures undergone, registration, examinations, and medication.In total, positive staining of CAM5.2 was 145 of 604 (24%). Statistical analysis showed that the expression of CAM5.2 had no relationship with sex, age, tumor differentiation, tumor size, tumor-node-metastasis (TNM) classification, and lymph node metastasis, but it was significantly associated with poor prognosis of overall survival (P = .0041) and disease-free survival (P = .0048) in ESCC patients.Herein, we report for the first time that the high expression of the CAM 5.2 is an independent predictor of poor prognosis in patients with ESCC.


Asunto(s)
Biomarcadores/análisis , Neoplasias Esofágicas/clasificación , Carcinoma de Células Escamosas de Esófago/complicaciones , Queratinas/análisis , Queratinas/genética , Adulto , Anciano , Biopsia/métodos , Biopsia/estadística & datos numéricos , China , Estudios de Cohortes , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Inmunohistoquímica/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Transcriptoma
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