Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment strategy for mesenchymal tumors of the gastrointestinal tract is based upon typing of the tumor. Especially differential diagnosis of gastrointestinal stromal tumors (GISTs) to leiomyomas is crucial for determining radicality of surgery. L1 cell adhesion molecule (CD171) plays an essential role in tumor progression. The aim of this study was to determine expression of L1 in GISTs, smooth muscle tumors, desmoid-type fibromatosis and peripheral nerve sheath tumors (PNSTs). We retrospectively analyzed a total of 129 surgically resected primary tumors or metastases of 72 GISTs, 29 smooth muscle tumors, seven PNSTs and 21 desmoid-type fibromatosis by immunohistochemistry for c-kit, CD34, smooth muscle actin, desmin, vimentin, S-100 and L1 expression. L1 expression was detected in 53 (74%) of 72 GISTs but in none of 29 smooth muscle tumors or 21 desmoid-type fibromatosis (P<0.01 by Fisher's test). In all, four (57%) of seven peripheral nerve sheath tumors were L1-positive. Survival analysis of 55 surgically completely resected GISTs presenting without metastasis at initial diagnosis revealed no tumor-specific death among L1-negative patients (P=0.13 by log-rank test; median follow-up time 41 months) and one recurrence was observed (P=0.12). Interestingly high levels of L1 were seen in tumor vascular endothelial cells of smooth muscle tumors and PNSTs, but not in GISTs. Our data show that L1 is highly expressed in GISTs but not in smooth muscle tumors and desmoid-type fibromatosis being important differential diagnoses. The trend towards a reduced survival of L1-positive patients in this study has to be further evaluated in future trials with higher patient numbers.
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PMID:L1 (CD171) is highly expressed in gastrointestinal stromal tumors. 1640 Mar 20

Angiogenesis is the process in which endothelial cells divide and migrate to form new capillaries, which support the continued growth of tumor through blood flow. Cancer-induced angiogenesis in general represents results of increased expression of angiogenic factors such as VEGF or decreased expression of anti-angiogenic factors, or a combination of both events. Numerous reported studies have demonstrated that angiogenesis plays an important role in tumor progression and metastasis of the great majority of human solid tumors. Furthermore, the quantitation of tumor angiogenesis in resected specimens of human tumor or surgical pathology specimens contribute to assessment of biological behavior and/or clinical outcome of the patients with cancer. Therefore, it is very important to assess the status of angiogenesis or cancer-induced vessels in resected tumor or surgical pathology specimens including those before and after the neoadjuvant therapy. It then becomes very important for pathologists involved in this evaluation to determine which methods to use in order to obtain accurate and reproducible results. In this short review, the status of an analysis of angiogenesis in surgical pathology specimens through analyzing vascular density or vasculatiry using immunohistochemical staining of CD34, a specific immunohistochemical marker for endothelial cells and subsequent evaluation of immunoreactivity in surgical pathology specimens will be summarized.
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PMID:Pathological evaluation of angiogenesis in human tumor. 1650 3

Dermatofibrosarcoma protuberans (DFSP) is a superficial tumor characterized by high rates of local recurrence and a small risk of metastasis. Fibrosarcomatous (FS) areas rarely arise in DFSP, and considerable controversy exists as to whether these tumors have a higher risk of metastasis than the typical DFSP. The aim of this study was to reappraise the prognostic significance of FS changes in DFSP by analyzing 41 patients from the consultation files of our institution. The study included 23 females and 18 males, with a median age of 48 years (range, 16-100 years). Eighteen lesions were located on the trunk, 16 on the extremities, and 7 on the head/neck region. All tumors were treated with local excision, and the surgical margins were considered positive for tumor in 22 of 39 cases (56%). Fibrosarcomas arose de novo in 38 cases and as a recurrence in 3 cases. All tumors involved the dermis and subcutis, and the FS component comprised 5% to 95% of the tumor area (median, 60%). Mitotic rates of the FS component (median, 20 mitoses/10 high-power fields [HPFs]; range, 5-48/10 HPFs) were considerably higher than those of the neighboring DFSP component (0-2 mitoses/10 HPFs). Immunohistochemical analyses showed that CD34 expression was stronger and more extensive in the DFSP component (97% positive; median intensity, 3+) than in the FS component (81% positive; median intensity, 2+). The MIB-1 labeling index was higher in the FS areas (median, 20%; range, 5%-45%) than in the DFSP areas (<3%). Expression of p53 was present in 92% of the FS areas and in only 3% of adjacent DFSP areas. Follow-up data revealed that 8 patients had local recurrences, 4 patients (10%) had metastases, and 2 patients died of disease. None of the variables evaluated, including margin status, FS proportion, and mitotic count, correlated with disease progression. We demonstrate that FS change in DFSP is a form of tumor progression that carries an increased risk of metastasis over classic DFSP and is associated with gains of p53 mutations and increased proliferative activity.
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PMID:The prognostic significance of fibrosarcomatous transformation in dermatofibrosarcoma protuberans. 1662 88

Objective. Information on angiogenesis in parathyroid pathology is scanty and in particular no data are available in parathyroid carcinomas. The aim of this study was to analyze angiogenesis as microvascular density (MVD) in parathyroid neoplastic progression from normal gland to adenoma and carcinoma. Methods. Sections from formalin-fixed, paraffin-embedded specimens of 33 normal parathyroids, 43 sporadic parathyroid adenomas, and 6 parathyroid carcinomas were cut for immunohistochemistry using anti-endothelial marker CD34. MVD was evaluated in each specimen as number microvessels per mm2. MVD data were compared with some anatomoclinical parameters as tumor size, serum calcium, and parathyroid hormone (PTH) level. Results. All normal parathyroid glands, all carcinomas, and 8 adenomas out of 43 (18%) showed MVD less than 100 microvessels/mm2 (median 70.8; 95%CI 66.9-88.5); in the majority of parathyroid adenomas (n = 35; 82%) the number of microvessels/mm2 was higher than 100 (median 188.3; 95%CI 174.9-210.1). In adenomas both preoperative serum intact PTH concentration and the diameters were significantly and inversely related to the microvessel density (r = 0.320, p < 0.05 and r = 0.334, p < 0.05, respectively). Conclusions. This study shows that in parathyroid adenomas MVD is heterogeneous and negatively related to the endocrine activity (secretory status and tumor size). Therefore, angiogenesis in parathyroid adenomas and carcinomas appears to be an early event, which does not follow a parallel increase in size.
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PMID:Microvessel density in human normal and neoplastic parathyroids. 1715 50

Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion.
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PMID:SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. 1736 30

The aim of this study was to assess the significance of expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and associated proteins in pancreatic ductal adenocarcinoma (PDA) and their impact on prognosis. Expression of HIF-1alpha, vascular endothelial growth factor (VEGF), glucose transporter-1 (Glut-1), survivin, CD34 and Ki-67 and apoptotic cells was demonstrated by immunohistochemistry or TUNEL in 58 PDAs and 20 normal pancreatic tissue samples. Our results show positivity of HIF-1alpha, VEGF, Glut-1 and survivin in 70.7%, 77.6%, 67.2% and 84.5% of the patients with PDA, respectively, which is significantly higher than in the normal counterparts. Expression of HIF-1alpha correlated positively with VEGF and Glut-1 expression but not with survivin. Strong HIF-1alpha expression associated with decreased apoptotic index and increased intratumoral microvessel density. Higher HIF-1alpha, VEGF and Glut-1 expression significantly associated with advanced tumor stage and lymph node metastasis. Patients with high HIF-1alpha, VEGF and Glut-1 expressing tumors had a poorer overall survival. Furthermore, Cox regression analysis showed that HIF-1alpha is a prognostic marker of borderline significance while VEGF was important in predicting poor outcome. These results suggest that over-expression of HIF-1alpha may play an important role in cancer progression through up-regulation of VEGF and Glut-1 in PDA patients. HIF-1alpha and VEGF are potential candidates for predicting survival.
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PMID:Expression of hypoxia-inducible factor-1 alpha and associated proteins in pancreatic ductal adenocarcinoma and their impact on prognosis. 1748 56

We analyzed the tumor vascularization in carcinomas ex-pleomorphic adenoma (CXPA) to investigate the angiogenic switch during the malignant transformation of pleomorphic adenoma (PA) to carcinoma and during tumor progression. In eight cases of early CXPA (intracapsular and minimally invasive tumors), eight of advanced CXPA (widely invasive tumors), and ten of PA without malignant transformation, tumor vascularization was assessed in histological samples by measuring total microvascular area (TVA) and microvessel density (MVD) using CD34 and CD105 antibodies. MVD for CD105 increased significantly during tumor progression, whereas this was not the case for CD34 MVD. Comparing widely invasive CXPA with and without myoepithelial differentiation, CXPA with myoepithelial differentiation showed a significantly lower number of CD105 positive vessels but revealed higher TVA values. In these tumors, the neoplastic cells usually formed larger hypovascularized aggregates that were often surrounded by large-sized vessels. In conclusion, the antibody CD105 reveals an angiogenic switch during the progression from adenoma to carcinoma in salivary glands. The degree of angiogenesis and the total vascular area have distinctive patterns in CXPA with and without myoepithelial differentiation. Low angiogenesis associated with high TVA value is more characteristic of CXPA with myoepithelial differentiation.
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PMID:Angiogenic switch during tumor progression of carcinoma ex-pleomorphic adenoma. 1759 87

Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial neoplasm of the gastrointestinal tract and show a predilection for the stomach. Most are detected because of symptoms, but some are incidental findings at autopsy or surgery for other reasons. Incidental GISTs tend to be smaller at diagnosis, but even small (<1 cm) GISTs have been shown to harbor activating KIT mutations at rates similar to advanced GISTs. However, the prevalence and characteristics of small GISTs in surgical resections of the esophagogastric junction (EGJ) remains unclear. We studied 150 esophagogastric resections for esophageal or EGJ carcinomas (100 with preoperative chemoradiation and 50 untreated cases) that had been extensively embedded for histologic examination (mean 30 sections/case). Number, size, morphology, and location of all GISTs and leiomyomas were recorded. All potential GISTs were evaluated with CD117 and CD34 immunohistochemistry, and a subset (35) leiomyomas with smooth muscle actin, desmin, and CD117. We found 18 incidental GISTs in 15 of 150 (10%) patients; 3 patients harbored 2 separate lesions. Prevalence of GIST was identical in treated (10 of 100) and untreated (5 of 50) cases. All (100%) showed positivity for both CD117 and CD34 and all were of spindle cell morphology. Lesions ranged from 0.2 to 3.0 mm in size (mean 1.3 mm). Eight (44%) were based in the outer muscularis propria, 7 (39%) in inner muscularis, and 3 (17%) between the muscle layers. The lesions tended to cluster near the EGJ, with 8 (44%) on the gastric side, 9 (50%) on the esophageal side, and 1 (6%) undetermined owing to overlying ulceration. Leiomyomas were even more common than GIST, occurring in 47% of patients (44% of treated and 52% of untreated, P=0.39), with a mean of 3 leiomyomas per patient (range 1 to 13) and mean size of 1.7 mm (range 0.2 to 12 mm). Unlike colorectal leiomyomas, most (91%) EGJ leiomyomas were located in the inner muscularis propria and only rarely (1%) in muscularis mucosa. These results suggest that GIST and leiomyoma are common incidental "seedling" lesions of the EGJ, found in 10% and 47% of patients undergoing surgery for esophageal carcinoma. The common occurrence of microscopic GISTs compared with the rarity of clinically manifest and malignant esophagogastric GISTs suggests that additional genetic or epigenetic alterations must happen for neoplastic progression.
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PMID:"Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction. 1805 18

Pancreatic cancer is a frequent cause of cancer-related mortality and has an extremely poor prognosis. To evaluate the efficacy of allogeneic hematopoietic SCT with reduced-intensity conditioning (RICT) against pancreatic cancer, we analyzed the clinical data of 22 patients. After a fludarabine-based conditioning regimen followed by the infusion of PBSCs, all but two achieved engraftment. Complete, partial and minor response was observed in 1, 2 and 2 patients, respectively, with an overall response rate of 23%. Median survival was only 139 days and the major cause of death was tumor progression. Poor performance status before RICT and a lower number of infused CD34-positive cells were associated with shorter survival after RICT. Patients who developed chronic GVHD tended to survive longer than those who did not. These findings support the investigation of a novel treatment strategy to enhance the immunological effect against pancreatic cancer.
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PMID:Allo-SCT using reduced-intensity conditioning against advanced pancreatic cancer: a Japanese survey. 1839 87

The DPC4 influences tumourigenesis and tumor progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of DPC4 is related to the angiogenesis in lung cancer and whether it could be involved in its clinical behaviour. Immunohistochemistry revealed that DPC4 was expressed at high level in normal broncho-tracheal epithelium, but at low level in tumor tissues, and closely correlated with tumor lymph node metastasis. This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high DPC4 expression demonstrated low VEGF expression and low MVD (microvessel density) labelled with CD34. In addition, DPC4 siRNA in A549 cells also showed that DPC4 could decrease VEGF protein and mRNA expression, and increase TSP1 protein and mRNA expression. Our findings indicated that DPC4 might be an important biomarker for malignant transformation and be involved in preventing the tumor metastasis by inhibiting tumor angiogenesis.
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PMID:Expression of DPC4/Smad4 in non-small-cell lung carcinoma and its relationship with angiogenesis. 1850 44


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