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1.
Angiogenesis ; 22(3): 441-455, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31161471

RESUMEN

The origin of blood and lymphatic vessels in high-grade serous adenocarcinoma of ovary (HGSOC) is uncertain. We evaluated the potential of cancer stem cells (CSCs) in HGSOC to contribute to their formation. Using spheroids as an in vitro model for CSCs, we have evaluated their role in primary malignant cells (PMCs) in ascites from previously untreated patients with HGSOC and cell lines. Spheroids from PMCs grown under specific conditions showed significantly higher expression of endothelial, pericyte and lymphatic endothelial markers. These endothelial and lymphatic cells formed tube-like structures, showed uptake of Dil-ac-LDL and expressed endothelial nitric oxide synthase confirming their endothelial phenotype. Electron microscopy demonstrated classical Weibel-Palade bodies in differentiated cells. Genetically, CSCs and the differentiated cells had a similar identity. Lineage tracking using green fluorescent protein transfected cancer cells in nude mice confirmed that spheroids grown in stem cell conditions can give rise to all three cells. Bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor inhibited the differentiation of spheroids to endothelial cells in vitro. These results suggest that CSCs contribute to angiogenesis and lymphangiogenesis in serous adenocarcinoma of the ovary, which can be inhibited.


Asunto(s)
Adenocarcinoma/patología , Linfangiogénesis , Neoplasias Quísticas, Mucinosas y Serosas/patología , Células Madre Neoplásicas/patología , Neovascularización Patológica/patología , Neoplasias Ováricas/patología , Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/ultraestructura , Ascitis/metabolismo , Ascitis/patología , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Biomarcadores de Tumor/metabolismo , Vasos Sanguíneos/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Células Endoteliales/metabolismo , Femenino , Humanos , Proteínas de Neoplasias/metabolismo , Neoplasias Quísticas, Mucinosas y Serosas/irrigación sanguínea , Neoplasias Quísticas, Mucinosas y Serosas/ultraestructura , Células Madre Neoplásicas/ultraestructura , Neoplasias Ováricas/irrigación sanguínea , Neoplasias Ováricas/ultraestructura , Pericitos/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
2.
Ultrastruct Pathol ; 41(1): 62-66, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28029275

RESUMEN

Ovarian mature cystic teratoma (OMCT) is an ovarian benign neoplasm with excellent prognosis presenting components of the three germinal layers. However, transformation into a malignant neoplasm is a rare event (so-called somatic transformation). In most of the cases, the malignant component expresses as epidermoid carcinoma, but occasionally central nervous system tumors occur. Some of the previously reported tumors are astrocytoma, glioblastoma, and ependymoma. Somatic transformation of OMCT into an oligodendroglioma is exceptional. We report a 19-year-old female with a left OMCT with an area of oligonedroglial cells proliferation characterized by immunohistochemical studies with positivity for GFAP and S100, with a low Ki67 index (5%). Additionally, electron microscopy revealed oligodendrocytes with parallel bundles of cytoplasmic intermediate filaments, confirming the oligodendroglial nature of the proliferation. The patient was treated only with left oophorectomy, and three and half years after surgery, there is no evidence of disease.


Asunto(s)
Biomarcadores de Tumor/análisis , Proliferación Celular , Inmunohistoquímica , Microscopía Electrónica , Neoplasias Quísticas, Mucinosas y Serosas/diagnóstico , Oligodendroglioma/diagnóstico , Neoplasias Ováricas/diagnóstico , Teratoma/diagnóstico , Femenino , Humanos , Neoplasias Quísticas, Mucinosas y Serosas/química , Neoplasias Quísticas, Mucinosas y Serosas/cirugía , Neoplasias Quísticas, Mucinosas y Serosas/ultraestructura , Oligodendroglioma/química , Oligodendroglioma/cirugía , Oligodendroglioma/ultraestructura , Neoplasias Ováricas/química , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/ultraestructura , Ovariectomía , Valor Predictivo de las Pruebas , Salpingectomía , Teratoma/química , Teratoma/cirugía , Teratoma/ultraestructura , Resultado del Tratamiento , Adulto Joven
3.
Hum Pathol ; 55: 174-81, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27237368

RESUMEN

Stratified mucin-producing intraepithelial lesion (SMILE) is considered to be a variant of adenocarcinoma in situ (defined as intraepithelial malignant glandular epithelium without invasion) or adenosquamous carcinoma in situ of the uterine cervix. However, recent study suggested that SMILE is more similar to high-grade squamous epithelial lesion by their immunohistochemical findings. An invasive form of SMILE "invasive stratified mucin-producing carcinoma (ISMC)" has been also proposed, but immunohistochemical features are not well documented. Therefore, this study aimed to clarify the immunohistochemical characteristics of SMILE and ISMC. Twelve cases of SMILE were found among 445 patients (2.7%) with high-grade intraepithelial lesions or invasive carcinomas, 3 of whom had solely intraepithelial disease with SMILE component (mean age, 37 years; range, 30-48 years) and 9 with invasive carcinomas (mean age, 47 years; range, 37-66 years; including ISMC). Immunohistochemically, SMILE and ISMC were diffusely positive for p16 and CAM5.2, focally for IMP3, and almost negative or only focally positive for p63. Nuclear signals in SMILE and invasive carcinomas were detected by human papillomavirus (HPV) in situ hybridization; 5 cases showed HPV16 and/or HPV18 polymerase chain reaction products. The ultrastructural study of 1 case showed surface microvilli and small vacuolar structure in SMILE; ISMC had mucous-like vacuoles, many mitochondria and intracytoplasmic lumen but lacked tonofilament. These findings were more similar to adenocarcinoma in situ or adenocarcinoma than squamous intraepithelial lesion or squamous cell carcinoma. We suggest that SMILE is an intraepithelial neoplasm and ISMC is an invasive form of SMILE.


Asunto(s)
Biomarcadores de Tumor/análisis , Inmunohistoquímica , Microscopía Electrónica de Transmisión , Neoplasias Quísticas, Mucinosas y Serosas/química , Neoplasias Quísticas, Mucinosas y Serosas/ultraestructura , Lesiones Intraepiteliales Escamosas de Cuello Uterino/metabolismo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/ultraestructura , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , ADN Viral/genética , Femenino , Pruebas de ADN del Papillomavirus Humano , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Neoplasias Quísticas, Mucinosas y Serosas/clasificación , Neoplasias Quísticas, Mucinosas y Serosas/virología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Lesiones Intraepiteliales Escamosas de Cuello Uterino/clasificación , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Terminología como Asunto , Neoplasias del Cuello Uterino/clasificación , Neoplasias del Cuello Uterino/virología , Adulto Joven
4.
Eur J Gynaecol Oncol ; 22(2): 110-5, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11446472

RESUMEN

Ovaries removed at 1,050 autopsies (accidental deaths) and from 300 patients with various benign gynaecological diseases were studied in search of the incipient benign epithelial tumors. One percent of the ovaries contained incipient mucinous tumors, 1.1%--Brenner tumors, 0.5%--endometrioid tumors. The exact percentage of the serous tumors was difficult to establish because of the absence of morphological criteria that distinguish these tumors from tumor-like conditions (inclusion cysts). The mucinous and Brenner tumors, as well as some serous tumors were located deep in the medullary or hilar regions of the ovary and were not connected to the covering of the ovary. The theory of incessant ovulation that links ovulatory damage of the ovarian surface with the initiation of neoplastic growth does not explain the genesis of all epithelial tumors. It is more likely that the latter two types arise in other parts of the female gonad. The process of morphogenesis of epithelial benign tumors is closely related to stromal alterations, specific for each histogenetic entity.


Asunto(s)
Tumor de Brenner/patología , Neoplasias Quísticas, Mucinosas y Serosas/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Tumor de Brenner/ultraestructura , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Quísticas, Mucinosas y Serosas/ultraestructura , Neoplasias Glandulares y Epiteliales/ultraestructura , Neoplasias Ováricas/ultraestructura , Lesiones Precancerosas/patología , Lesiones Precancerosas/ultraestructura
5.
Semin Diagn Pathol ; 15(1): 2-20, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9503503

RESUMEN

Predominantly cystic renal neoplasms have been the source of diagnostic confusion and controversy. In this review, the authors analyze the clinical and pathological features of four entities that consistently exhibit a diffusely cystic growth pattern, are strikingly similar in their gross appearances, and are not separable by preoperative imaging studies. Based on the literature, this review concludes that tumors in young children that have been classified as cystic nephroma and cystic partially differentiated nephroblastoma likely represent a single entity, and all should be considered highly cystic Wilms' tumors with little or no capacity for invasion or metastasis and diagnosed as cystic partially differentiated nephroblastoma. Conversely, cystic nephroma in adults has no discernible connection with Wilms' tumor or nephrogenic rests and should be considered a benign composite neoplasm of stroma and epithelium of unknown histogenesis, which may rarely become malignant with secondary development of a sarcoma. Multilocular cystic renal cell carcinoma appears to be unrelated to cystic nephroma and if the following criteria are met, it appears to be a neoplasm with an intrinsically cystic growth pattern, and no, or at most little, malignant potential: (1) an expansile mass is surrounded by a fibrous wall, (2) the interior of the tumor entirely is composed of cysts and septa with no expansile solid nodules, and (3) the septa contain aggregates of epithelial cells with clear cytoplasm. Cystic hamartoma of the renal pelvis is a rare, complex tumor composed of stroma with a prominent smooth muscle component and a variety of epithelial elements.


Asunto(s)
Neoplasias Renales/clasificación , Neoplasias Renales/patología , Neoplasias Quísticas, Mucinosas y Serosas/patología , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/ultraestructura , Adolescente , Adulto , Anciano , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/ultraestructura , Niño , Preescolar , Femenino , Hamartoma/patología , Hamartoma/ultraestructura , Humanos , Inmunohistoquímica , Lactante , Enfermedades Renales Quísticas/patología , Enfermedades Renales Quísticas/ultraestructura , Neoplasias Renales/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Neoplasias Quísticas, Mucinosas y Serosas/ultraestructura , Distribución por Sexo , Tumor de Wilms/patología , Tumor de Wilms/ultraestructura
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