RESUMEN

Lobular neoplasia (LN) and columnar cell alterations (CCAs) may share similar genetic abnormalities, but there is no appreciable literature that addresses the simultaneous occurrence of these lesions in breast core biopsy (CNB) specimens or resection specimens. Three groups of breast tissue were examined: group 1, 68 CNB specimens targeted for "suspicious" microcalcifications (Breast Imaging Reporting and Data System [BI-RADS] 4) and diagnosed with LN; group 2, 2,516 CNB reports for a 1-year period; and group 3, 400 consecutive breast carcinoma resection specimens analyzed for LN and CCAs within the vicinity of carcinoma. In group 1, LN was associated with CCAs in 54% of cases (37/68). In group 2, LN was found in association with CCA in 1.3% of cases (32/2,516). In group 3, 13.0% of cases of CCAs (52/400) were associated with LN. Our study suggests the association of these two lesions in breast tissue is nonrandom and that they may have a common progenitor pathway of neoplastic development.

Asunto(s)

Neoplasias de la Mama/patología , Mama/patología , Carcinoma in Situ/patología , Carcinoma Lobular/patología , Biopsia , Femenino , Humanos , Hiperplasia/patología , Neoplasias Primarias Múltiples/patología

RESUMEN

Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neuronally differentiated cells. Pulmonary neuroendocrine carcinomas such as carcinoid tumors and small cell carcinomas are derived from neuroendocrine cells. We hypothesize that neuroendocrine cells may also express MAP-2, and therefore, MAP-2 may be used as a marker for pulmonary carcinomas of neuroendocrine differentiation. To investigate the utility of using MAP-2 expression to separate pulmonary neuroendocrine from non-neuroendocrine tumors, we examined the expression of MAP-2 immunohistochemically in 100 cases of pulmonary carcinomas. The immunoperoxidase method with antigen retrieval was used to characterize the expression of MAP-2, chromogranin, synaptophysin, and neuron-specific enolase in 25 small cell carcinomas, 25 carcinoid tumors, 25 adenocarcinomas, and 25 squamous cell carcinomas. All tumors were lung primaries. All 25 cases of carcinoid tumors (100%) as well as 23 of 25 cases (92%) of small cell carcinomas were positive for MAP-2. Four of 25 cases (16%) of adenocarcinomas were positive for MAP-2 and synaptophysin. Among the 25 squamous carcinomas, 4 cases (16%) were positive for MAP-2, 2 cases (8%) were positive for synaptophysin, 11 cases (44%) were positive for neuron-specific enolase, and none was positive for chromogranin. In conclusion, MAP-2 is a new sensitive and specific marker for the pulmonary tumors of neuroendocrine differentiation. We recommend that MAP-2 be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors.

Asunto(s)

Proteínas Asociadas a Microtúbulos/análisis , Biomarcadores de Tumor/análisis , Tumor Carcinoide/metabolismo , Tumor Carcinoide/patología , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Pequeñas/patología , Cromograninas/análisis , Humanos , Inmunohistoquímica , Pulmón/química , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Fosfopiruvato Hidratasa/análisis , Sensibilidad y Especificidad , Sinaptofisina/análisis

RESUMEN

Papillary fibroelastomas are rare and benign cardiac tumors that typically affect the cardiac valves. To the best of our knowledge, the English literature contains only 1 case report of pulmonary valve fibroelastoma diagnosed by echocardiogram and confirmed by surgical resection. There is a paucity of pathology literature on this subject. We describe an additional case of pulmonary valve fibroelastoma diagnosed by transesophageal echocardiography and magnetic resonance imaging confirmed by pathologic examination in a patient who also had a thymoma.

Asunto(s)

Neoplasias Cardíacas/patología , Válvula Pulmonar , Ecocardiografía Transesofágica , Femenino , Neoplasias Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/patología , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad

RESUMEN

This review examines the use of self-assembly in the fabrication of ceramic mesostructures, emphasizing the use of amphiphilic surfactants and block copolymers. The association between this area of research and biomimetics is discussed, linking developments in synthetic self-assembly with biomineralization. The fabrication of hierarchical structures through the use of simultaneous processing is shown to be a necessary condition for applications of this new technology.

RESUMEN

We report a small-cell variant of synovial sarcoma examined by fine-needle aspiration (FNA) biopsy. The patient is a 23-yr-old female who had a synovial sarcoma involving the left infratemporal region, diagnosed at 7 yr of age, followed by a metastatic lesion involving the lung and chest wall 16 yr later. The chest wall metastases was sampled by FNA biopsy. The aspirate consisted of numerous, small, round cells with very high nuclear-to-cytoplasmic ratios. The cytomorphologic features could potentially be confused with other pediatric small round cell tumors. Ancillary studies demonstrated positive staining of the neoplastic cells for cytokeratin, epithelial membrane antigen (EMA), and CD99. The differential diagnosis of other small round cell tumors that may be mistaken for the small-cell variant of synovial sarcoma are presented. We believe that this is the first FNA report detailing the cytologic and ancillary features of the small-cell variant of synovial sarcoma.

Asunto(s)

Neoplasias de Cabeza y Cuello/diagnóstico , Sarcoma Sinovial/diagnóstico , Adulto , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Carcinoma de Células Pequeñas/diagnóstico , Niño , Diagnóstico Diferencial , Femenino , Neoplasias de Cabeza y Cuello/química , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Neoplasias del Mediastino/química , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/secundario , Proteínas de Neoplasias/análisis , Sarcoma Sinovial/química , Sarcoma Sinovial/secundario , Hueso Temporal

RESUMEN

Catechol-O-methyltransferase (COMT) plays both a regulatory and protective role in catechol homeostasis. It contributes to the regulation of tissue levels of catecholamines and catecholestrogens (CEs) and, by blocking oxidative metabolism of catechols, prevents endogenous and exogenous catechols from becoming a source of potentially mutagenic electrophiles. Evidence implicating CEs in carcinogenesis, in particular in the hamster kidney model of estrogen-induced cancer, has focused attention on the protective role of COMT in estrogen target tissues. We have previously reported that treating hamsters with estrogens causes translocation of COMT to nuclei of epithelial cells in the renal cortex, the site of CE biosynthesis and where the cancers arise. This finding suggested that nuclear COMT may be a marker of a threat to the genome by catechols, including CEs. It is postulated that CEs play a role in the genesis of breast cancer by contributing to a state of chronic oxidative stress that is presumed to underlie the high incidence of this disease in the United States. Therefore, here we used immunocytochemistry to re-examine human breast parenchyma for nuclear COMT. In addition to confirming previous reports of cytoplasmic COMT in mammary epithelial cells, we identified nuclear COMT in foci of mammary epithelial cells in histologically normal breast tissue of virtually all control (macromastia) and cancer patients and in breast cancer cells. There was no correlation between tissue histology and the numbers of cells with nuclear COMT, the size of foci containing such cells, or intensity of nuclear COMT immunostaining. The focal nature of the phenomenon suggests that nuclear COMT does not serve a housekeeping function but that it reflects a protective response to an increased local catechol load, presumably of CEs and, as such, that it may be a characteristic of the population of women studied who share the same major risk factor for developing breast cancer, that of living in the industrialized West.

Asunto(s)

Neoplasias de la Mama/enzimología , Mama/enzimología , Catecol O-Metiltransferasa/metabolismo , Núcleo Celular/enzimología , Adolescente , Adulto , Mama/citología , Neoplasias de la Mama/patología , Células Epiteliales/enzimología , Femenino , Humanos , Persona de Mediana Edad , Distribución Tisular

RESUMEN

Fine-needle aspiration of the breast is one of the most common procedures performed on patients with a palpable breast mass. The pathologist needs to be aware of the diagnostic and prognostic parameters that must be included in the cytopathology report of breast carcinomas. These fundamental parameters include tumor type, nuclear grade of the carcinoma, and hormone receptor status.

Asunto(s)

Biopsia con Aguja , Neoplasias de la Mama/patología , Neoplasias de la Mama/química , Ciclo Celular , Núcleo Celular/patología , Femenino , Humanos , Cinética , Pronóstico , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis

RESUMEN

The cell types that may be present in any fine-needle aspiration biopsy (FNAB) of breast include epithelial cells (EC), myoepithelial cells (MEC), bipolar stromal cells (BSC), vascular pericytes/endothelial cells (VPEC), and adipose cells (AC). The recognition of most of these benign cellular elements in aspirates of the breast is relatively straightforward, based on distinct cytomorphologic criteria. However, there is controversy regarding the recognition of MEC because BSC are often referred to as MEC by cytopathologists. It is important to identify MEC in breast aspirates, because their presence has been associated with benign epithelial proliferations. In this study we used immunocytochemical methods on archival cytology slides with antibodies specific for MEC, calponin, and smooth muscle myosin heavy chain (SMMHC), to determine the distribution of MEC in FNAB of the breast and to ascertain the distribution of MEC in in situ and invasive carcinomas. Fifteen benign FNABS of breast and corresponding tissue biopsies were obtained along with 10 malignant FNABS and corresponding excisional breast biopsies from 1989-1993. Calponin and SMMHC antibodies were used on archival alcohol-fixed Papanicolaou-stained direct smears as well as the corresponding tissue sections. The distribution and pattern of positive immunostaining with both antibodies were recorded on the benign elements and the carcinomas for both cytologic and histologic slides. Benign breast tissues demonstrated strong continuous immunostaining for calponin and SMMHC of MEC. The interlobular stromal cells as well as intralobular stromal cells showed no immunostaining with either antibody. In cytologic preparations, MEC staining with calponin and SMMHC appeared as spindle cells between epithelial cells or along the edges of the epithelial groups. The bipolar stromal cells did not stain with either antibody. The tissues with DCIS (ductal carcinoma in situ) often showed the presence of MEC with strong calponin immunostaining, but sometimes the immunostaining was discontinuous or entirely absent around markedly dilated ducts. The SMMHC antibody was invariably negative, with architectural DCIS in dilated ducts. Two cases of DCIS with prominent periductal fibrosis or inflammation were positive for calponin, but the periductal stromal cells were calponin- and SMMHC-negative. Invasive carcinoma was negative for both calponin and SMMHC, but areas of DCIS were often positive in a discontinuous pattern. In conclusion, 1) Benign cellular elements from breast tissue FNAB showed strong continuous decoration of MEC with both calponin and SMMHC. Vascular pericytes and vascular smooth muscle were positive for both antibodies, but these cells were not observed in the FNAB. Benign proliferative epithelium showed no local increase in MEC with either antibody. Bipolar stromal cells in tissue and smears did not stain for MEC antibodies. 2) BSC did not correspond morphologically to MEC, and were not decorated with calponin or SMMHC. 3) Calponin-positive MEC were commonly associated with in situ ductal lesions, although they may at times have been discontinuous or absent entirely. DCIS may be recognized in FNAB by the presence of calponin-positive MEC associated with tumor cell groups. 4) Invasive carcinomas were invariably negative for MEC with these antibodies.

Asunto(s)

Enfermedades de la Mama/patología , Mama/química , Proteínas de Unión al Calcio/metabolismo , Músculo Liso/química , Cadenas Pesadas de Miosina/metabolismo , Biopsia con Aguja , Mama/patología , Endotelio Vascular/patología , Células Epiteliales/patología , Femenino , Humanos , Inmunohistoquímica , Proteínas de Microfilamentos , Células del Estroma/patología , Calponinas

RESUMEN

Multiloculated thymic cysts are uncommon lesions that can be either acquired or associated with malignancies. This report describes the fine-needle aspiration (FNA) cytology of a mediastinal seminoma with prominent cystic change, confirmed by surgical pathology examination and ancillary studies performed on both the cytology and tissue specimens. The FNA cytology revealed clusters of malignant oval-to-polygonal-shaped cells with large oval nuclei possessing prominent nucleoli set in a pale-to-eosinophilic cytoplasm. These cells were surrounded by a dense lymphoid infiltrate along with a few noncaseating granulomas. The large malignant seminoma cells stained positive for placental alkaline phosphatase (PLAP) and negative for both low molecular and broad-spectrum cytokeratin. The differential diagnosis of malignancies associated with thymic cysts is presented. To the best of our knowledge, this is the first report of aspiration cytology of a mediastinal seminoma associated with a multilocular cyst.

Asunto(s)

Biopsia con Aguja , Quiste Mediastínico/complicaciones , Quiste Mediastínico/patología , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/patología , Seminoma/complicaciones , Seminoma/patología , Humanos

Asunto(s)

Sustitutos de Huesos/uso terapéutico , Cuidados Críticos/métodos , Atención Perioperativa/métodos , Costillas/anomalías , Costillas/cirugía , Titanio , Preescolar , Humanos , Masculino , Atención Perioperativa/enfermería , Radiografía , Costillas/diagnóstico por imagen

RESUMEN

The diagnostic process begins with triage of the FNAB, depending on the patient's problem. Portions of the specimen can then be set aside for appropriate immunocytochemistry, hormone receptors analysis, electron microscopy, flow cytometry, or molecular studies. Microscopic evaluation, as in surgical pathology, begins with scanning objective examination of tissue architecture, followed by study of cellular characteristics, and finally the nuclear features. Cytopathology and surgical pathology are no longer distinct entities.

Asunto(s)

Biopsia con Aguja , Neoplasias/diagnóstico , Patología Quirúrgica/métodos , Núcleo Celular/patología , Femenino , Humanos , Masculino , Pronóstico

RESUMEN

Some cytologic specimens may be limited in quantity, and this may hamper or preclude the performance of immunocytochemistry (ICC) in cases where more than one antibody (ab) is required by ICC to arrive at a definitive diagnosis. There is very little information in the cytology literature regarding the use of ICC for specimens that are limited in quantity. In this study, we describe a method, derived from the principles of double immunolabelling, whereby more than one ab test can be repeatedly used on the same Papanicolaou stained slide. Multiple cytologic scrape preparations fixed in 95% ethanol were obtained from fresh surgical specimens including carcinomas of the breast, endometrium, stomach, ovary and colon. Nonneoplastic tissues included tonsil (2), lymph node (2) and myometrium. Papanicolaou stained slides or unstained slides were subjected to two sequential ICC procedures, the first in which the ab was known to be nonreactive with the cells (insulin, glucagon, or somatostatin) and the second in which the ab was known to be positive in the cells. Positive controls for the known positive abs included a single-step ICC procedure as well as the tissue section. The test abs included CAM 5.2, AE1/3, K903, LCA, L26, UCHL-1, s-100, mCEA, GCDFP-15, vimentin, muscle specific actin and desmin. Identical two-step ab procedures were carried out on the tissues from the same surgical specimens. For Papanicolaou stained cytologic specimens, abs were reactive and gave excellent results for the repeat second-step ICC method. There was no false positive or false negative staining. This "repeat ICC" method also gave excellent results on the tissue sections. Immunocytochemistry can be performed more than once on the very same cytologic specimen if the initial ICC antibody attempt is negative. This method may be especially useful in situations where more than one antibody is needed on a very limited cytologic sample size.

Asunto(s)

Inmunohistoquímica/métodos , Manejo de Especímenes/métodos , Anticuerpos Monoclonales/metabolismo , Carcinoma/metabolismo , Carcinoma/patología , Citodiagnóstico , Femenino , Humanos , Neoplasias/metabolismo , Neoplasias/patología

RESUMEN

INTRODUCTION: For cytologic specimens, the vast majority of immunocytochemical studies (ICC) are performed on non-gynecologic specimens for diagnostic purposes, and they can be performed on unstained or previously stained direct smears. Although the ThinPrep processor (TPP) has been approved for the preparation of non-gynecologic specimens, there is scant literature describing the utility of ICC methodology on cytology specimens fixed and processed by this method. MATERIALS AND METHODS: Forty-one fresh specimens were obtained from the surgical gross room and aspirated or scraped to collect cells for thin layer (TL) and direct smears (DS). Specimens included a variety of neoplastic and nonneoplastic samples that were either Papanicolaou (P) stained or unstained (US). One group of US TL slides was subjected to antigen retrieval (AR). Staining was graded semiquantitatively. Each sample acted as its own control. Antibodies (abs) included: CAM5.2, AE1/3, K903, vimentin, MSA, desmin, s-100, HMB45, PSA, PAP, chromogranin, NSE, insulin, synaptophysin, pCEA, mCEA, mCEAD14, LCA, L26, UCHL-1, OPD-4, thyroglobulin, GCDFP, ER/PR, laminin, collagen IV, PLAP, HCG, CD68, HAM56, and MAC387. RESULTS: Semiquantitative staining overall results comparisons: TLP > DSP TLP < DSP TLP = DSP TLUS > DSUS 11/25 (44%) 6/25 (24%) 8/25 (32%) 9/24 (38%) TLUS < DSUS TLUS = DSUS 3/24 (12%) 12/24 (50%) TLP Vs. TLUS TLP > TLUS TLP < TLUS TLP = TLUS 8/41 (20%) 9/41 (22%) 24/41 (58%) There were five false-negative results, 2 with TL and 3 with DS, and 1 false-positive TL. DISCUSSION: Immunocytochemistry performed on the ThinPrep Processor showed equal or greater intensity and distribution of proper staining when compared to direct smears with the following advantages: (1) cleaner background, easier to interpret; (2) less abs required in a smaller area; (3) IPX can be done on Papanicolaou-stained thin layer slides; (4) thin layer slides can be modified for multiple abs tests; (5) additional thin layer slides can be prepared for ICC bases on needs. No significant differences of immunostaining were seen when comparing thin layer Papanicolaou-stained and unstained slides. Antigen retrieval offered no advantage in this study.

Asunto(s)

Técnicas Histológicas , Inmunohistoquímica/métodos , Anticuerpos/análisis , Biopsia con Aguja , Femenino , Humanos , Masculino , Neoplasias/inmunología , Neoplasias/patología

Asunto(s)

Biopsia con Aguja/métodos , Técnicas Citológicas , Patología Quirúrgica/métodos , Patología/métodos , Biopsia con Aguja/instrumentación , Técnicas Citológicas/instrumentación , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Microscopía Electrónica , Neoplasias/diagnóstico , Neoplasias/patología , Neoplasias/ultraestructura , Patología/instrumentación , Patología Quirúrgica/instrumentación

RESUMEN

PURPOSE: We tested whether the types of inflammatory cells seen on bladder biopsies were associated with other clinical features and urinary markers of interstitial cystitis. MATERIALS AND METHODS: Bladder biopsies from 30 interstitial cystitis patients were evaluated by immunohistochemical staining for T cells, B cells, macrophages and human leukocyte antigen-DR positive cells. These findings were tested for associations with clinical features and urinary markers of interstitial cystitis using alpha = 0.01 because multiple tests were performed. RESULTS: Overall severity of inflammation was significantly associated with age at symptom onset, symptom relief after bladder distention and urinary interleukin-6 levels. Patients with severe inflammation had trends toward smaller bladder capacity under anesthesia, increased bladder vascularity and mucosal cracks, lower urinary MUC-1 glycoprotein levels and absence of bloating as a symptom. B cell staining was significantly associated with severe inflammation, symptom relief after distention and absence of bloating as a symptom. T cell staining was significantly associated with severe inflammation and age at symptom onset. Human leukocyte antigen-DR staining had trends with symptoms, including presence of bloating, constant urge to void and absence of burning. Macrophage staining did not associate with any features tested at the alpha = 0.05 level. CONCLUSIONS: Interstitial cystitis patients with severe inflammation have different age, treatment response and urinary marker levels than those with mild inflammation. These findings suggest that the 2 patient groups have different underlying pathophysiologies. The significant associations for T and B cell staining were similar to those for overall inflammation.

Asunto(s)

Linfocitos B , Cistitis Intersticial/patología , Macrófagos , Linfocitos T , Cistitis Intersticial/inmunología , Antígenos HLA-DR , Humanos

RESUMEN

Almost all diseases affecting the native kidney may recur in the transplanted kidney, with one of the most frequent being recurrent glomerulonephritis. Among the glomerulonephritides, membranoproliferative glomerulonephritis (MPGN), immunoglobulin A nephropathy (IgA), and focal-segmental glomerulosclerosis (FSGS) have the highest rates of recurrence. Here we report a patient who, after living-related kidney transplantation, suffered allograft loss shortly after surgery due to recurrence of glomerulonephritis. Two weeks prior to transplant nephrectomy light microscopic examination of the allograft biopsy failed to show glomerulonephritis. Subsequent histopathology of the transplant nephrectomy specimen demonstrated a crescentic form of type I MPGN following withdrawal of cyclosporin A (CsA) and intense course or oral steroid therapy. The entity of recurrent type I MPGN in kidney transplantation is reviewed, and a possible protective role of CsA against rapidly progressive crescentic type I MPGN is explored.

Asunto(s)

Ciclosporina/uso terapéutico , Glomerulonefritis Membranoproliferativa/cirugía , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Femenino , Glomerulonefritis Membranoproliferativa/patología , Supervivencia de Injerto , Humanos , Riñón/patología , Donadores Vivos , Persona de Mediana Edad , Recurrencia

RESUMEN

Giant cell neoplasms of the pancreas are rare tumors of uncertain histogenesis. Mutation of the KRAS oncogene is common in typical pancreatic duct adenocarcinoma. We have analyzed DNA from five pancreatic tumors with giant cells for mutations in the KRAS oncogene and found alterations of the second position of codon 12 in each case (four G > A transitions and one G > C transversion). The common mutation pattern in tumors with giant cells and duct adenocarcinoma suggests a common route to malignant transformation and may indicate a shared histogenesis. We also tested 11 cases of malignant fibrous histiocytoma, a histological mimic of pleomorphic giant cell tumor, for mutations in the KRAS oncogene. The absence of KAS mutations in each of the malignant fibrous histiocytomas (MFHs) and in other histologically similar tumors may provide assistance in the differential diagnosis of pleomorphic pancreatic tumors.

Asunto(s)

Adenocarcinoma/genética , Genes ras/genética , Tumor Óseo de Células Gigantes/genética , Tumores de Células Gigantes/genética , Conductos Pancreáticos , Neoplasias Pancreáticas/genética , Adenocarcinoma/patología , Anciano , Femenino , Tumor Óseo de Células Gigantes/patología , Tumores de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología

RESUMEN

To address the isoenzyme-specific involvement of protein kinase C (PKC) in breast cancer biology, hormone-responsive MCF-7 breast cancer cells were infected with either PKC-alpha or -beta 1 cDNAs subcloned in the retroviral expression vector pMV7. Several stable clones of PKC-overexpressing cells were generated. Western analysis revealed cross-regulation between the alpha and beta isoforms, because induction of overexpression of one up-regulated the other. Overexpression of the alpha and beta isoenzymes, on the other hand, did not affect the already high endogenous expression of the novel delta, epsilon, eta, and zeta isoforms. Compared with control clones, PKC-alpha- and -beta-overexpressing MCF-7 cells exhibited more drastic morphological changes in response to phorbol 12-myristate 13-acetate administration characterized by cellular flattening and vacuolization. More importantly, induction of PKC-alpha and -beta overexpression induced a less aggressive biological behavior, which was characterized by reduced in vitro invasiveness and markedly diminished tumor formation and growth in nude mice. These in vivo findings can probably best be explained by the dramatic down-regulation of estrogen receptor levels observed in tumors derived from PKC-alpha-infected MCF-7 cells. Our data clearly show that it is possible to induce a less aggressive breast cancer phenotype by altering PKC isoenzyme expression.

Asunto(s)

Neoplasias de la Mama/patología , Carcinoma/patología , Isoenzimas/fisiología , Proteína Quinasa C/fisiología , Animales , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/etiología , Carcinoma/enzimología , Carcinoma/etiología , División Celular/efectos de los fármacos , Tamaño de la Célula , Femenino , Expresión Génica , Isoenzimas/biosíntesis , Isoenzimas/genética , Isoenzimas/metabolismo , Ratones , Ratones Desnudos , Fenotipo , Proteína Quinasa C/biosíntesis , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Proteína Quinasa C beta , Proteína Quinasa C-alfa , Acetato de Tetradecanoilforbol/farmacología , Células Tumorales Cultivadas , Vacuolas/patología , Vacuolas/ultraestructura

RESUMEN

The expression of aromatase by breast cancer cells and the role of locally produced estrogen in the stimulation of tumor growth has been controversial. The present study was performed to determine the site of aromatization in human breast cancers, using both immunocytochemistry and in situ hybridization. The functional significance of locally produced estrogens on growth of the tumor was addressed by measuring aromatase activity and a marker of proliferation (PCNA score). In addition, histocultures of some tumors were carried out to investigate whether testosterone aromatization could stimulate tumor proliferation. Of the 19 tumors investigated, 10 (52.6%) showed significant immunoreactivity to antiaromatase antibody in the cytoplasm of tumor epithelial cells and in surrounding stromal cells. The presence of aromatase mRNA detected by ISH was also located in tumor epithelial cells and stromal cell, and the pattern of expression was the same as with immunocytochemistry. In the ten tumors that showed immunoreaction to aromatase, the average aromatase activity measured in cryosections was 286.5 +/- 18.6 (SE) fmol estrogen/mg protein.h, whereas in nine tumors with weak aromatase immunoreaction, the enzyme activity was 154.7 +/- 19.3 (SE) fmol estrogen/mg protein-h (P < 0.05). The mean PCNA score was 33.8 +/- 5.1 (SE)% in strongly stained tumors and 20.8 +/- 2.0 (SE)% in weakly stained tumors (P < 0.05). Aromatase activity level and PCNA score were significantly correlated. In histoculture of four tumors, estradiol increased the incorporation of [3H]-thymidine into DNA. In two of these tumors, aromatase activity was high and [3H]-thymidine incorporation into DNA was also stimulated by testosterone. In the other two tumors that had low aromatase activity, no such stimulation occurred with testosterone. The results indicate that aromatase is expressed mainly in tumor epithelial cells and that sufficient amounts of estrogen are synthesized by the tumor to produce a proliferative response. It is concluded that estrogen synthesis by cancer cells could play a important role in promoting growth in a significant proportion of breast tumors.

Asunto(s)

Aromatasa/biosíntesis , Neoplasias de la Mama/enzimología , Regulación Enzimológica de la Expresión Génica , Biosíntesis de Proteínas , ARN Mensajero/biosíntesis , Transcripción Genética , Secuencia de Bases , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/enzimología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/enzimología , Carcinoma Lobular/patología , Cartilla de ADN , Sondas de ADN , Epitelio/enzimología , Epitelio/patología , Estradiol/biosíntesis , Estrona/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Posmenopausia , Premenopausia , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis

RESUMEN

In the case described here, the patient's initial presentation suggested ovarian carcinoma. She had recurrent ascites, a pelvic mass, elevated CA-125, and extensive peritoneal carcinomatosis with transitional cell histology. The presence of hematuria prompted a cystoscopy, which revealed the true site of origin to be the urinary bladder rather than ovaries. This presentation is extremely rare for bladder cancer. Since transitional cell tumors from the bladder have a much worse prognosis than those of ovarian origin, it is important to identify the primary site correctly. Therefore, cystoscopy is essential for patients with hematuria, and should be considered in cases of apparent primary peritoneal carcinoma with transitional cell histology.

Asunto(s)

Carcinoma de Células Transicionales/patología , Neoplasias Ováricas/patología , Neoplasias de la Vejiga Urinaria/patología , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad