RESUMEN
We have established a cell line derived from a pleural effusion of breast scirrhous carcinoma. This cell line presented immunohistochemically negative for estrogen receptor and slightly positive for progesterone receptor, and positive for c-erbB/HER2/neu. However the original tumor was found to be positive for estrogen receptor and progesterone receptor and slightly positive for c-erbB/HER2/neu expression. Enzyme and electrochemiluminescence immunoassays of tumor markers in the conditioned medium by the cell line revealed they secrete CA15-3, NCC-ST-439 and HER2 protein. We believe the cell line will contribute to the therapeutic study of malignant breast cancer.
Asunto(s)
Adenocarcinoma Escirroso , Biomarcadores de Tumor/análisis , Neoplasias de la Mama , Derrame Pleural Maligno , Receptor ErbB-2 , Adenocarcinoma Escirroso/genética , Adenocarcinoma Escirroso/patología , Adenocarcinoma Escirroso/ultraestructura , Animales , Antígenos de Carbohidratos Asociados a Tumores/análisis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/ultraestructura , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Cariotipificación , Ratones , Persona de Mediana Edad , Mucina-1/análisis , Trasplante de Neoplasias , Derrame Pleural Maligno/citología , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patología , Receptor ErbB-2/análisis , Receptores de Estrógenos , Receptores de ProgesteronaRESUMEN
We successfully established a breast scirrhous carcinoma cell line (designated as NABCA) derived from metastatic tumors of the lymph node. The cells grew as multi-layered cultures without contact inhibition. The population doubling time was approximately 66 h. G-band karyotype of NABCA revealed 66% diploid, XX. Surprisingly, the cells had a number of secretory granules and straight microvilli as a brash border. In heterotransplantation, the cells produced a tumor resembling the original tumor. The NABCA is sensitive to Adriamycin (doxorubicin; KYOWA HAKKO KOGYO, Tokyo, Japan) and Taxol (paclitaxel; Bristol-Myers KK, Tokyo, Japan). This cell line is useful for studying the mechanism of lymphatic metastasis and susceptibility of anticancer drugs in human breast scirrhous cancer.
Asunto(s)
Adenocarcinoma Escirroso/patología , Neoplasias de la Mama/patología , Técnicas de Cultivo de Célula/métodos , Adenocarcinoma Escirroso/genética , Adenocarcinoma Escirroso/secundario , Adenocarcinoma Escirroso/ultraestructura , Animales , Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/ultraestructura , División Celular , Línea Celular Tumoral , Resistencia a Antineoplásicos , Femenino , Humanos , Cariotipificación , Metástasis Linfática , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Persona de Mediana Edad , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
Whether argyrophilic nucleolar organizer region (AgNOR) is a predictor of prognosis in breast cancer is controversial. The semiquantitative procedure used to calculate interphasic argyrophilic dots optically is neither reliable nor reproducible. We measured the mean area of AgNOR dots, the mean AgNOR area per nucleus (MA), and the mean AgNOR number per nucleus (MN) by automated image analysis in specimens from 131 patients with breast cancer. Higher MA (> 7.41 microns2), detected in 22 (16.8%) of 131 patients, did not correlate with clinicobiologic variables, except for DNA ploidy status. Overall survival was significantly better in patients with lower MA than in those with higher MA. On multivariate analysis, MA was a significant independent factor, followed by nodal status. These findings indicate that expression of AgNOR should be evaluated in terms of area occupied and that the mean area of AgNOR per nucleus (MA) is an important prognostic factor in the overall survival of breast cancer patients.
Asunto(s)
Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/ultraestructura , Carcinoma Ductal de Mama/ultraestructura , Núcleo Celular/ultraestructura , Región Organizadora del Nucléolo/ultraestructura , Adenocarcinoma Escirroso/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , ADN de Neoplasias/análisis , Femenino , Citometría de Flujo , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Tinción con Nitrato de PlataRESUMEN
The three-dimensional structure of the collagen networks in human gastric carcinoma was examined by scanning electron microscopy (SEM) after treatment with the cell-maceration method using a low temperature NaOH solution. Based on stromal content, the poorly differentiated adenocarcinoma can be divided into the medullary carcinoma area and the scirrhous carcinoma area. In the medullary carcinoma, the collagen sheath around the small tumor cell acinus formed spherical chambers (20-30 microns in diameter) with fenestrations (about 5 microns in diameter) connecting the chambers. The collagen sheath was composed of fine collagen fibrils (about 50 nm in diameter). In the scirrhous area, there was abundant fibrous stroma composed of thicker collagen fibrils (about 100 nm in diameter). Tiny tumor cell nests were sporadically seen in the fibrous stroma. These tumor nests were surrounded by collagen fibrils (about 50 nm in diameter). In the moderately differentiated tubular adenocarcinoma, the tumors were surrounded by spherical, ovoid or irregular shaped thick collagen sheaths (50-200 microns in diameter), which were composed of loosely packed 50 nm collagen fibrils. In well differentiated tubular adenocarcinoma, tumor glands were surrounded by spherical, ovoid or irregularly-shaped thick collagen sheaths (50-200 microns in diameter), composed of densely arranged fine collagen fibrils. In papillary carcinoma, the collagen sheaths were nipple-shaped. They were composed of very densely arranged fine collagen fibrils (about 50 nm in diameter).
Asunto(s)
Colágeno/ultraestructura , Microscopía Electrónica de Rastreo , Neoplasias Gástricas/ultraestructura , Adenocarcinoma/ultraestructura , Adenocarcinoma Papilar/ultraestructura , Adenocarcinoma Escirroso/ultraestructura , Carcinoma Medular/ultraestructura , HumanosRESUMEN
Reported is the case history of a 58-year-old woman with a lump in the left breast. The tumor was composed of two nodules, sharing a common portion. Grossly, one was an irregular hard tumor that was grayish in color, and the other was a well circumscribed cystic tumor that showed necrosis and a hemorrhage that had filled it with a reddish soft mass. Light microscopically, combined features of a scirrhous carcinoma and of an osteosarcoma were observed in each nodule, but the common portion was consistent with a metaplastic carcinoma, with cancer cells and sarcoma-like cells closely mingled. An ultrastructural study showed that the sarcoma-like cells were composed of polymorphic cells that resembled osteoblasts, myofibroblasts, osteoclasts, histiocytes, and undifferentiated tumor cells. Immunohistochemically, vimentin and alpha 1-antitrypsin in the sarcoma-like cells were positive, suggesting these cells were of a mesenchymal rather than of an epithelial origin.
Asunto(s)
Adenocarcinoma Escirroso/patología , Neoplasias de la Mama/patología , Osteosarcoma/patología , Adenocarcinoma Escirroso/análisis , Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/análisis , Neoplasias de la Mama/ultraestructura , Femenino , Humanos , Técnicas para Inmunoenzimas , Microscopía Electrónica , Persona de Mediana Edad , Osteosarcoma/análisis , Osteosarcoma/ultraestructura , Vimentina/análisis , alfa 1-Antitripsina/análisisRESUMEN
Bilateral breast tumors with a histologically scirrhous pattern were conclusively diagnosed as gastric carcinoma metastatic to the breast using mucosubstance histochemistry and electron microscopy. The majority of the carcinoma cells gave histochemically positive reactions for galactose oxidase-Schiff, stable class III con A, and high-iron diamine-alcian blue (HID-AB). Also electron microscopically, numerous HID-positive mucus droplets (sulfomucin) were seen in the carcinoma cells. These findings invalidated the possibility that the carcinomas were primary breast cancer. The practical applications of distinctive patterns of mucus secretion are discussed.
Asunto(s)
Adenocarcinoma Escirroso/secundario , Neoplasias de la Mama/secundario , Neoplasias Gástricas/patología , Adenocarcinoma Escirroso/análisis , Adenocarcinoma Escirroso/diagnóstico , Adenocarcinoma Escirroso/patología , Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/análisis , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Neoplasias de la Mama/ultraestructura , Femenino , Histocitoquímica , Humanos , Microscopía Electrónica , Persona de Mediana Edad , Moco/análisis , Neoplasias Gástricas/análisis , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/ultraestructuraRESUMEN
The morphological differences between cells of a human scirrhous gastric carcinoma cell line (KATO-III) cultured in plastic dishes and in collagen-coated dishes were examined by phase-contrast and electron microscopy. When KATO-III cells were inoculated into plastic dishes, a few cells became attached to the surface of the dishes and the rest remained in suspension. However, when they were inoculated into collagen-coated dishes, they all remained in suspension. In both types of dish, most of the cells in suspension were single although a few were in clusters. The cells in suspension in collagen-coated dishes differed in morphology from those in the plastic dishes. They had abundant cytoplasm, well-developed Golgi complexes, and many microvillus-like cell protrusions. Moreover, they had hemidesmosome-like and desmosome-like structures on their surface and an increased amount of intracytoplasmic desmosome-like structures. The cells in clusters in the collagen-coated dishes were closely connected by junctional complexes, such as tight junctions, desmosomes and interdigitations, whereas those in plastic dishes were linked only by desmosomes. These results suggest that collagen affects the morphology of human scirrhous carcinoma cells.
Asunto(s)
Adenocarcinoma Escirroso/ultraestructura , Membrana Celular/ultraestructura , Colágeno/farmacología , Neoplasias Gástricas/ultraestructura , Células Tumorales Cultivadas/ultraestructura , Adhesión Celular , Desmosomas/ultraestructura , Humanos , Uniones Intercelulares/ultraestructura , Microscopía Electrónica , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The tumour stroma in cases of ductal infiltrating carcinoma of the mammary gland contains substantial amounts of collagen type I trimer, besides the regular collagen types. Reconstituted collagen trimer consists of fibrils that are significantly thinner than reconstituted fibrils of type I collagen. The axial periodicity is somewhat longer due to widening of the c-d and d-e regions. Transmission EM of the tumours shows characteristic phenomena at the stromal-tumour cell junctions: frequent absence of a basal lamina and thin disordered collagen fibrils that show frequent direct contacts with tumour cells. On the basis of literature data concerning the interaction between stroma and epithelia under physiological and pathological conditions it is hypothesized that the interaction of collagen type I trimer fibrils with tumour cells is instrumental in augmenting tumour cell progression and that the trimer may provide contact guidance for invasive growth.
Asunto(s)
Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/ultraestructura , Carcinoma Intraductal no Infiltrante/ultraestructura , Colágeno/análisis , Femenino , Humanos , Sustancias Macromoleculares , Microscopía ElectrónicaRESUMEN
Detailed light and electron microscopic, and immunohistochemical observations were made on the distribution and morphological characteristics of myoepithelial cells in the 53 cases of breast cancer. In non-invasive carcinoma, myoepithelial cells in the normal duct were found to be remaining at the outer margin of the cancer nests, but neoplastic myoepithelial cells were not detected in the carcinoma tissue. In invasive carcinoma, a small number of fluorescence-weakly-positive cells could be observed in more than 50% of medullary-tubular carcinoma, in all cases of papillary-tubular carcinoma, and two of three cases of invasive lobular carcinoma. Almost all of these cells were ultrastructurally intermediate cells which have the morphological characteristics of both epithelial cell and myoepithelial cell. Fluorescence-positive cells were observed in all cases of scirrhous carcinoma. Moreover, these cells showed a stronger fluorescence than that of other types of carcinoma and were ultrastructurally more similar to normal myoepithelial cell. The tumor cells having myoepithelial characteristics in invasive carcinoma showed a stronger tendency for arranging at the margin of carcinoma nests in contact with the stroma. The results of the present study indicate that in invasive carcinoma of the breast, neoplastic myoepithelial cells could be demonstrated together with ductal epithelial cells and as to its histogenesis, there is a possibility that breast cancer develops from common stem cells which have the ability of differentiating into both epithelial and myoepithelial cell because of the presence of intermediate cells.
Asunto(s)
Neoplasias de la Mama/ultraestructura , Carcinoma/ultraestructura , Adenocarcinoma/ultraestructura , Adenocarcinoma Escirroso/ultraestructura , Anticuerpos , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Microscopía Electrónica , Miosinas/inmunología , Células MadreRESUMEN
To elucidate the histogenesis of gastric scirrhous cancer, the promotion of collagen production by normal human skin fibroblasts (HSF-1) with human gastric cancer cells (KATO-III, MKN-45 and MKN-28) was investigated by direct coculture and parabiotic culture. Argyrophilic collagenous fibers were demonstrated among fibroblasts on both direct cocultures and parabiotic cultures of the fibroblasts with gastric cancer cells. Microscopic examination showed that these fibers appeared earlier and were more abundant and thicker in direct cocultures and parabiotic cultures than in single cultures of fibroblasts. Gastric cancer cells in single or parabiotic culture did not form argyrophilic fibers. For quantitative proof of the promotion of collagen production by fibroblasts with gastric cancer cells, hydroxyproline produced by fibroblasts was measured. Much higher fibroblast hydroxyproline values were obtained in parabiotic cultures with gastric cancer cell lines than in single cultures of HSF-1. Moreover, the rate of collagen synthesis by HSF-1 was much higher than that of any gastric cancer cell line tested. These results demonstrate that gastric cancer cells enhance collagen production by fibroblasts in vitro. This finding suggests that they may produce a factor promoting fibroblast collagen synthesis and that this may contribute to the formation of stromal collagen in human gastric scirrhous cancer.
Asunto(s)
Adenocarcinoma Escirroso/metabolismo , Colágeno/biosíntesis , Piel/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma Escirroso/patología , Adenocarcinoma Escirroso/ultraestructura , Línea Celular , Técnicas de Cultivo , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/ultraestructura , Humanos , Microscopía Electrónica , Piel/patología , Piel/ultraestructura , Neoplasias Gástricas/patología , Neoplasias Gástricas/ultraestructuraRESUMEN
A scanning electron microscopic technique for the examination of bulk, fresh, hydrated human tissue is described. Samples of fresh tissue are frozen in liquid nitrogen against a mirror-finished copper block and planed in a cryoultramicrotome before transfer to a low temperature scanning electron microscope. After sublimation of water from the specimen surface, the tissue is examined in secondary electron and backscattered electron modes. Adjacent pieces of tissue, and those retrieved after backscattered electron observation, can be readily prepared for and examined by light and by conventional transmission electron microscopy. The method has been tested with multiple blocks taken from 6 cases of human breast carcinoma. In the backscattered electron mode, the infiltrating columns of neoplastic cells can be distinguished from mammary adipose and fibrous tissue. Within a carcinoma, the collagenous stroma, carcinoma cells, and perivascular and perineural infiltrates can be identified. These features have been contrasted with those obtained by light microscopy, by low temperature scanning, and by transmission electron microscopy. This use of backscattered electron imaging for the investigation of unfixed hydrated tissue offers the possibility that the technique could be of considerable value in the microscopy of very small samples in which, because of a need for subsequent biochemical, histochemical, and immunologic investigation, fixation and dehydration are to be avoided.
Asunto(s)
Neoplasias de la Mama/ultraestructura , Microscopía Electrónica de Rastreo/métodos , Adenocarcinoma Escirroso/ultraestructura , Biopsia , Mama/ultraestructura , Carcinoma Intraductal no Infiltrante/ultraestructura , Femenino , HumanosRESUMEN
Scirrhous carcinoma of the breast was divided into 2 subtypes and studied electron microscopically. One type consisted of severe scleroid infiltration of papillotubular carcinoma into the stromal tissues, the other of scirrhous carcinoma in a narrow sense. In the former type, heterochromatins, light and dark cells, and intercellular lumens were observed. In the latter type, euchromatins, light cells and the absence of intercellular lumens were noted. Many intracytoplasmic lumens were observed in scirrhous carcinoma of the latter type. Thus, the 2 subtypes of scirrhous carcinoma differed greatly from each other electron microscopically due to different cellular activities. In discussing prognosis, the 2 subtypes of scirrhous carcinoma of the breast should be differentiated.
Asunto(s)
Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/ultraestructura , Femenino , Humanos , Líquido Intracelular/citología , Microscopía Electrónica , Invasividad Neoplásica , PronósticoRESUMEN
The ultrastructural analysis of the three main histological forms (adenocarcinoma, scirrhous carcinoma, and solid carcinoma) of infiltrative mammary gland carcinomas with regard to the histological grades of malignancy (I, II, III) has revealed that with the increase of the histological grade of malignancy the number of ultrastructurally differentiated cells decreased. No correlation between histological and ultrastructural findings has been found, however. In histologically highly differentiated adenocarcinomas of grade I of malignancy ultrastructurally nondifferentiated cells could mainly be found, but ultrastructurally differentiated cells predominated in a number of cases of histologically nondifferentiated scirrhous and solid carcinomas of grade III of malignancy. Some cases of histologically similar carcinomas showed predominance of ultrastructural differentiated cells, others of ultrastructurally nondifferentiated cells. These results should be taken into account in ultrastructural diagnosis and evaluation of prognostic significance of electron microscopic findings.
Asunto(s)
Adenocarcinoma Escirroso/ultraestructura , Adenocarcinoma/ultraestructura , Neoplasias de la Mama/ultraestructura , Adenocarcinoma/patología , Adenocarcinoma Escirroso/patología , Mama/patología , Neoplasias de la Mama/patología , Femenino , Humanos , Microscopía Electrónica , Estadificación de NeoplasiasRESUMEN
Improved early diagnosis and utilization of new procedures for postoperative treatment of breast cancer have made it possible, especially in the case of small tumors, to depart from the orthodox radical operative procedures. In planning a proper therapeutic approach, preoperative diagnosis plays an ever increasing role. In a prospective study 103 cases with cytologically and histologically verified carcinoma of the breast were subjected to cytological grading. The parameter for the grading included the dissociation range and polymorphism of the nuclei, the occurrence of nucleoli and the size of the nuclei. The low-risk-group was comprised mainly of older patients with small cell unimorphous, histologically scirrhous or tubular carcinomas. The high-risk-group was comprised mainly of younger patients predominantly with large call polymorphous, histologically solid carcinomas. The results are expected to give insight into tumor dynamics as well as to be to of therapeutic relevance.
Asunto(s)
Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/ultraestructura , Carcinoma/ultraestructura , Biopsia , Núcleo Celular/ultraestructura , Citodiagnóstico , Femenino , Humanos , Estudios ProspectivosAsunto(s)
Adenocarcinoma Escirroso/patología , Neoplasias de la Mama/patología , Adenocarcinoma Escirroso/ultraestructura , Neoplasias de la Mama/ultraestructura , Carcinoma/patología , Carcinoma/ultraestructura , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/ultraestructura , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Estudios ProspectivosRESUMEN
Eighteen argyrophil cell carcinomas in 101 early gastric carcinomas were explained histologically, ultrastructurally, and immunohistochemically for polypeptides, carcinoembryonic antigen (CEA), lysozyme, and human chorionic gonadotrophin (hCG). Seven of these 18 tumors had gastrin, and two of seven tumors also contained somatostatin. In all of these 18 tumors CEA were demonstrated. Seven had lysozyme and five of seven tumors also contained gastrin; hCG were present in four of the 18 tumors and two of four tumors had gastrin, CA, mucin, and lysozyme simultaneously. Argentaffin cells were found in seven of 18 tumors. Of the above seven tumors containing gastrin, three had argentaffin cells. Ultrastructurally, several types of secretory granules were noted and tumor cells resembling D1- or P cells were present in nine of the 18 tumors. Macroscopically, many of the tumors showed IIc or IIc + III type. Histologically, the 18 tumors consisted of six well differentiated adenocarcinomas and 12 poorly differentiated adenocarcinomas including signet-ring cell carcinoma. These 12 tumors frequently developed in the stomach of young females. In view of our previous investigations, it was suggested that the IIc-type argyrophil cell carcinoma histologically showing poorly differentiated adenocarcinoma may be related to scirrhous carcinoma of the stomach.
Asunto(s)
Adenocarcinoma/patología , Neoplasias Gástricas/patología , Adenocarcinoma/ultraestructura , Adenocarcinoma Escirroso/patología , Adenocarcinoma Escirroso/ultraestructura , Adulto , Anciano , Antígeno Carcinoembrionario/análisis , Gonadotropina Coriónica/análisis , Femenino , Gastrinas/análisis , Histocitoquímica , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Plata , Coloración y Etiquetado , Neoplasias Gástricas/ultraestructuraRESUMEN
Study of 14 human infiltrating breast carcinomas revealed new features that shed light on the pathogenesis of tumor stroma formation and on host immunologic defense mechanisms. Fibrin deposits were observed in the stroma of all tumors, particularly at their growing edge. Fibrin may have contributed both to tumor angiogenesis and, with organization, to the formation of the fibrous stroma characteristic of these and other scirrhous carcinomas. We previously proposed similar mechanisms for several animal tumors. All breast carcinomas studied elicited some degree of lymphocytic response at the tumor periphery; lymphocytes penetrated the fibrous tumor stroma poorly, did not exit in significant numbers from central tumor vessels, and, even when greatly outnumbering tumor cells locally, appeared relatively ineffective at tumor cell killing. Microvascular endothelial cell damage was frequently observed and may have been responsible for zones of tumor infarction. Similar observations have been made in skin allografts and animal tumors where rejection was effected principally by microvascular damage and subsequent tissue infarction, not by lymphocyte contact with individual epithelial target cells.
Asunto(s)
Adenocarcinoma Escirroso/patología , Neoplasias de la Mama/patología , Adenocarcinoma Escirroso/irrigación sanguínea , Adenocarcinoma Escirroso/ultraestructura , Adulto , Anciano , Animales , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/ultraestructura , Carcinoma Intraductal no Infiltrante/irrigación sanguínea , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/ultraestructura , Femenino , Fibrina , Técnica del Anticuerpo Fluorescente , Cobayas , Humanos , Linfocitos , Microscopía Electrónica , Persona de Mediana Edad , Vénulas/ultraestructuraRESUMEN
The surface ultrastructure of tissue-cultured cells derived from the pleural effusion of metastatic scirrhous breast carcinoma in the human MDF-7 cell line was studied by scanning electron microscopy. It was found to form monolayers of various colonies or collections of cells which were either separate or intimately adherent. The surface ultrastructure of the cells was found to be exclusively formed of microvilli. Data suggesting a diagnostic significance of microvilli in cancer cells were discussed. Observations were made which point to the existence of a compensatory absorptive functional activity exerted by the microvilli.