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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical, cytogenetic, histopathologic, and immunohistochemical data were obtained in a series of 11 small round cell tumors (SRCT) of bone and soft tissue with the translocation t(11;22) (q24;q12). Ten cases were primary in bone, and one was of extraskeletal origin. According to conventional histopathologic criteria, 10 cases were Ewing's sarcomas (ES) and one was a peripheral neuroectodermal tumor (PNET). Besides the t(11;22), six cases had additional chromosomal aberrations, including trisomy 7 and partial trisomy for the long arm of chromosome 1, which have both been described as nonspecific secondary abnormalities often associated with tumor progression. The tumors were screened for neural differentiation with an antibody panel consisting of neuron-specific enolase, S100 protein, Leu-7, chromogranin, synaptophysin, and neurofilament. Three cases of ES were positive for S100 protein. The PNET and one case of ES were positive for neuron-specific enolase. All of the remaining immunohistochemical stains were negative. Hence, five of 11 SRCT of bone or soft tissue with the t(11;22) showed morphologic and/or immunohistochemical evidence of neural differentiation. In this limited series of cases, no cytogenetic or prognostic differences could be demonstrated between cases with and without a neural phenotype. Our results support the hypothesis that SRCT of bone of soft tissue with the t(11;22) form a single biologic entity displaying varying degrees of neuroectodermal differentiation. The clinical significance of additional cytogenetic abnormalities and of morphologic or immunohistochemical evidence of neural differentiation in this group of tumors needs to be further studied.
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PMID:Neural differentiation in small round cell tumors of bone and soft tissue with the translocation t(11;22)(q24;q12): an immunohistochemical study of 11 cases. 217 3

The theory that poorly differentiated prostate carcinoma develops a neuroendocrine (NE) phenotype is controversial. Supportive data is variable with NE expression being observed in anywhere from 5% to 83% of prostate cancers. These percentages are derived from standard immunohistochemistry studies, which make no attempt to quantify the results. High-density tissue microarrays (TMAs), represent a novel method for evaluating up to 1000 tissue samples with a 0.6 mm diameter on a single glass slide. This high throughput technology for screening antibodies, however, requires validation to determine if TMAs are useful in evaluating heterogeneously expressed proteins such as the NE markers chromogranin A (CGA) and synaptophysin (SYN). This study compares results from standard slides to TMAs in 50 primary and metastatic prostate tumors taken from 12 rapid autopsies from men with hormone refractory prostate cancer. One hundred standard and 2 TMA slides were immunostained for CGA and SYN. Using standard slides, focal NE expression was seen in 1/12 primary prostate tumors. Overall, 13/100 (13%) standard slides showed focal NE expression for both primary and metastatic prostate tumors; NE expression was observed in 4/12 autopsy cases (33%) when all tumor sites per case were considered. 458 tissue elements (tumor and normal) were arrayed into one paraffin block. Seventy-three percent (332/458) of the elements placed into the TMA were confirmed histologically to represent tumor. Seventy-five percent (250/332) and 66% (218/332) could be evaluated for CGA and SYN expression, respectively. Six of the metastatic tumors expressed CGA and SYN or 2.4% (6/250; 95% CI = 0.9% to 5.2%) and 2.3% (6/218; 95% CI = 0.8% to 5.3%), respectively. In conclusion, only focal NE expression was observed by both methods (eg, standard and TMA slides). The focal expression in these advanced prostate tumors was unexpected given data from prostate tumor cell lines and animal models suggesting that progression to the NE phenotype parallels tumor progression. This study also supports the use of high density TMAs to screen for protein expression, even when expression is focal.
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PMID:Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. 1082 85

A 9-year-old girl with a 1-month history of generalized seizure presented with a distinctive tumor resembling pleomorphic xanthoastrocytoma. Neuroimagings showed a right frontotemporal lobe tumor. Histological examination of the resected tumor indicated similarity to pleomorphic xanthoastrocytoma without staining for glial fibrillary acidic protein. The neuronal immunoreactivity and ultrastructural features showed two discrepancies: Numerous cytoplasmic processes containing rich structures suspected to be microtubules and neurofilaments were present, but neurofilament protein 70 kd/200 kd staining was negative; and many tumor cells showed synaptophysin staining, but no synaptic structures or vesicles were observed. She suffered recurrence 14 months after the first surgery. The specimen from the second operation revealed no malignant transformation with a MIB-1 labeling index of 1.9%. Only 2 months after the second operation, there was a second recurrence. Irradiation was administered (60.2 Gy). Twenty-eight months later, no tumor progression was seen. This tumor was an unconventional type with "abortive" or "aberrant" neuronal differentiation or an extreme variant of pleomorphic xanthoastrocytoma.
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PMID:Distinctive pleomorphic xanthoastrocytoma-like tumor with exclusive abortive or aberrant neuronal differentiation and repeated recurrence--case report. 1237 98

We describe an unusual progression of astrocytoma into secondary glioblastoma exhibiting advanced neuronal immunophenotype. A tumor of the left frontal lobe of a 35-year-old man was diagnosed as astrocytoma. The tumor was treated by partial removal with postoperative chemoradiotherapy, followed by extensive removal of the residual regrowing tumor 5 month later. A secondary tumor was discovered and partially resected 8 years later, but the patient died 11 months following the operation due to extensive tumor progression showing subarachnoidal and intraventricular dissemination. The secondary tumor was small cell-predominant, highly proliferative tumor with an extremely high MIB-1 labeling index (80%). Unexpectedly, most of the tumor cells were positive for neuronal markers (synaptophysin and NeuN), but not for glial fibrillary acidic protein (GFAP). Retrospective examination of the original tumor revealed not only diffuse GFAP expression, but also neuronal marker expressions in small numbers of tumor cells that were hard to discriminate from the other cells on hematoxylin-eosin (HE) stain. This way of malignant progression of astrocytoma was quite unusual. Although the secondary tumor was classified as glioblastoma according to World Health Organization (WHO) classification (2000), it might be categorized into new variants of malignant glioneuronal tumors proposed recently.
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PMID:Secondary glioblastoma with advanced neuronal immunophenotype. 1596 44

Endocrine tumors are defined as neoplastic lesions resulting from the proliferation of cells engaged in an endocrine differentiation pathway, as shown by their expression of a set of specific markers, including true endocrine markers (such as chromogranine A) and neuro-endocrine markers, shared between neurons and endocrine cells (such as synaptophysin). The demonstration of the synthesis and secretion of one or several hormones is not necessary for the assessment of the endocrine nature of a tumor; only tumors associated with a clinical syndrome resulting from hormone overproduction can be said functioning endocrine tumors. Beyond their common features, endocrine tumors are characterized by a marked diversity, which results from the large functional, structural and embryological heterogeneity of normal endocrine cells. The natural history of endocrine tumors is also characterized by a marked heterogeneity in their evolution and rate of progression. While most endocrine tumors are locally and slowly evolving, some of them behave as truly malignant tumors, as shown by their capacity of metastatic dissemination and their fatal evolution. A better understanding of the cellular and molecular mechanisms involved in tumor progression and metastatic dissemination is necessary for the identification of new prognostic tools and novel therapeutic targets.
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PMID:[Endocrine tumors: biology and physiopathology]. 1673 72

Antiangiogenic therapy is a promising alternative for prostate cancer growth and metastasis and holds great promise as an adjuvant therapy. The present study evaluated the potential of stable expression of angiostatin and endostatin before the onset of neoplasia and during the early and late stages of prostate cancer progression in transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Groups of 5-, 10-, and 18-week-old male TRAMP mice received recombinant adeno-associated virus-6 encoding mouse endostatin plus angiostatin (E+A) by i.m. injection. The effects of therapy were determined by sacrificing groups of treated mice at defined stages of tumor progression and following cohorts of similarly treated mice for long-term survival. Results indicated remarkable survival after recombinant adeno-associated virus-(E+A) therapy only when the treatment was given at an earlier time, before the onset of high-grade neoplasia, compared with treatment given for invasive cancer. Interestingly, early-stage antiangiogenic therapy arrested the progression of moderately differentiated carcinoma to poorly differentiated state and distant metastasis. Immunohistochemical analysis of the prostate from treated mice indicated significantly lower endothelial cell proliferation and increased tumor cell apoptosis. Vascular endothelial growth factor receptor (VEGFR)-2 expression was significantly down-regulated in tumor endothelium after treatment but not VEGFR-1. Analysis of the neuroendocrine marker synaptophysin expression indicated that antiangiogenic therapy given at an early-stage disease reduced neuroendocrine transition of the epithelial tumors. These studies indicate that stable endostatin and angiostatin gene therapy may be more effective for minimally invasive tumors rather than advanced-stage disease.
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PMID:Effects of sustained antiangiogenic therapy in multistage prostate cancer in TRAMP model. 1757 46

The objective of this study was to investigate functional deficits and reactive peri-tumoral brain plasticity events in glioma-bearing rats. 9L gliosarcoma cells were implanted into the forelimb region of the sensorimotor cortex in Fischer rats. Control animals underwent the same operation without tumor implantation. Sensitive tests for detecting sensorimotor dysfunction, including forelimb-use asymmetry, somatosensory asymmetry, and vibrissae-evoked forelimb placing tests, were conducted. We found that tumor-bearing animals exhibited significant composite behavioral deficits on day 14 post-tumor injection compared to surgical controls. With the assistance of magnetic resonance imaging, we demonstrated a significant correlation between tumor volume and magnitude of somatosensory asymmetry, indicating that the somatosensory asymmetry test can provide an effective and efficient means to measure and predict tumor progression. Histopathological assessments were performed after the rats were sacrificed 14 days following tumor implantation. Immunostaining revealed that densities of microtubule-associated protein 2, glial fibrillary acid protein, von Willebrand factor, and synaptophysin were all significantly upregulated in the peri-tumoral area, compared to the corresponding region in surgical controls, suggesting synaptic plasticity, astrocyte activation and angiogenesis in response to tumor insult. Understanding the behavioral and bystander cellular events associated with tumor progression may lead to improved evaluation and development of new brain tumor treatments that promote, or at least do not interfere with, functional adaptation.
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PMID:Sensorimotor deficits associated with brain tumor progression and tumor-induced brain plasticity mechanisms. 1770 96

Neuroendocrine malignancies of the gastroenteropancreatic axis include carcinoid and pancreatic endocrine tumors. These heterogeneous neoplasms arise from the enterochromaffin cells of the gastrointestinal tract and the islet cells of the pancreas. Histologically, most well-differentiated endocrine tumors consist of small, round, monomorphic cells, arranged in islands or trabeculae, with a distinct "salt-and-pepper" pattern of nuclear chromatin. Chromogranin and synaptophysin are useful as immunohistochemical markers of neuroendocrine differentiation. Other common features include the capacity to secrete peptide hormones and biogenic amines. A relatively indolent growth rate is characteristic of most gastrointestinal neuroendocrine tumors, with the exception of poorly differentiated tumors which are usually aggressive. Treatment strategies are designed to limit tumor progression and palliate hormonal syndromes. This article reviews the diverse biologic characteristics of gastrointestinal neuroendocrine tumors and current treatment options for metastatic disease.
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PMID:Biology and treatment of metastatic gastrointestinal neuroendocrine tumors. 1925 90

Despite improvements in diagnosis of advanced prostate cancer (PCa), treatment is not efficient and 5-year survival is still low. Initially, the less abundant of cell types, neuroendocrine cells (NE), are involved in regulatory process but their physiological role is not fully understood. Among others, an increase in NE cells along with tumor progression has been commonly reported but their role in tumorigenesis or the molecular mechanisms of transdifferentiation is still a matter of debate. We have used human PCa cells (LNCaP) induced to differentiate to NE cells with several stimuli: androgen withdrawal, cyclic AMP or treatment with the antioxidant pineal hormone melatonin. PCa patients' specimens were also analyzed by western blotting and by immunocytochemistry. NE-like LNCaP cells express high levels of mitochondrial superoxide dismutase (MnSOD/SOD2) in addition to NE markers. MnSOD upregulation is mediated by NFkappaB transcription factor, mainly through p65 translocation into the nuclei. More importantly, overexpression of MnSOD induces the rise of NE-markers in LNCaP cells, showing that MnSOD upregulation might be instrumental for NE differentiation in PCa cells. Furthermore, MnSOD is highly expressed in advanced tumors of patients' when compared with control, nonpathological samples or with low-grade tumors, along with the presence of synaptophysin, a common NE marker. Also, fluorescence immunohistochemical analysis revealed that MnSOD colocalizes with NE markers in most of NE cells observed in PCa specimens. The present findings indicate that MnSOD is essential for NE transdifferentiation and mediates in part the differentiation process, which appears also to be critical in vivo.
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PMID:Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells. 1950 53

Large-cell neuroendocrine carcinoma of the colon is a rare entity with a prognosis that is usually poor due to the high likelihood of early metastasis. A 61-year-old man had surgery for colon cancer of the transverse colon and cecum. Microscopic examination of the tumor showed that the location was the proximal transverse colon, with small nests containing rosettes and palisading patterns of large tumor cells with faintly granular cytoplasm. The immunohistochemistry was positive for synaptophysin and chromogranins. The tumors were diagnosed as a large-cell neuroendocrine carcinoma of the colon. In addition, the tumor of the cecum showed microscopic findings consistent with a well-differentiated adenocarcinoma. The immunohistochemical panel showed that the tumor was negative for neuroendocrine markers. There were no clinical findings suggestive of hormone hypersecretion. Cancer metastasis was found in the peritoneum section of the small bowel. Postoperative chemotherapy was applied. The patient was alive with good performance after, and there was no sign of tumor progression. This is the first case of a synchronous large-cell neuroendocrine carcinoma and adenocarcinoma of the colon. The patient was treated successfully with debulking surgery and systemic chemotherapy.
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PMID:Synchronous large-cell neuroendocrine carcinoma and adenocarcinoma of the colon. 2047 25


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