Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal myofibroblasts are alpha-smooth muscle actin-positive stromal cells that exist as a syncytium with fibroblasts and mural cells in the lamina propria of the gut. Through expression and secretion of cytokines, chemokines, growth factors, prostaglandins, and basal lamina/extracellular matrix molecules, as well as expression of adhesion molecules and receptors for many of the same soluble factors and matrix, myofibroblasts mediate information flow between the epithelium and the mesenchymal elements of the lamina propria. With the use of these factors and receptors, they play a fundamental role in intestinal organogenesis and in the repair of wounding or disease. Intestinal neoplasms enlist and conscript myofibroblast factors and matrix molecules to promote neoplastic growth, carcinoma invasion, and distant metastases.
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PMID:Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. 1596 83

Uterine perivascular epithelioid cell tumor (PEComa) is very rare, and there have been only 27 reported cases. The differentiation of the tumor has been enigmatic, and the biologic behavior remains unclear. This study describes the clinical, histologic, and immunohistochemical features of four cases of uterine PEComa. The patients were 30, 32, 36, and 40 years old, and none of them had tuberous sclerosis complex. The size of the tumors ranged from 1 to 30 cm in diameter, and 3 of the 4 tumors were confined in the uterus. One tumor involved the left ovary and omentum. Microscopically, the tumors were characterized by an epithelioid arrangement of tumor cells, which had abundant clear to eosinophilic pale granular cytoplasm, and one tumor had moderately atypical nuclei. Coagulative necrosis was found in two cases. The mitotic figures ranged from 0 to 11 per 10 high power fields. Immunohistochemically, the tumors were positive for vimentin (4/4), HMB45 (4/4), h-caldesmon (4/4), alpha-smooth muscle actin (3/4), muscle actin (2/4), and desmin (3/4). They were uniformly negative for Melan A, CD10, and S-100 protein. Ultrastructural examinations were performed on one case and revealed no melanosomes, premelanosomes, or evidence of smooth muscle differentiation. One patient died of intestinal metastases 17 months after surgery. The other patients have been well with no evidence of disease 8, 12, and 36 months after surgery. Uterine PEComa should be regarded as tumors with an uncertain malignant potential until long-term outcome data for a larger number of patients become available.
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PMID:Perivascular epithelioid cell tumor of the uterus: report of four cases. 1617 79

Osteoclast-like giant-cell neoplasms of the urinary tract are rare. They are composed of ovoid or spindle-shaped mononuclear cells with evenly spaced osteoclast-like giant cells. Terminology, histogenesis, and biologic behavior of these tumors remain controversial. Six cases of osteoclast-like giant-cell neoplasms of the urinary tract were identified from the consultation files of two of the authors. Patients were all male and elderly (range 65-82), with the exception of one 39-year-old male. In all, 3/6 tumors developed in the bladder and 3/6 in the renal pelvis. Size ranged from 5 to 11 cm. One bladder and three renal pelvis tumors were high stage (pT3) at time of presentation. Adjacent to the osteoclast-like giant-cell neoplasm in the same specimen, all patients had urothelial carcinoma in situ and/or high-grade papillary urothelial carcinoma. Multinucleated cells had identical morphological and immunohistochemical properties of osteoclasts; positive for CD-68, LCA, CD51 and CD54, and negative for cytokeratins and EMA. Varying percentages of mononuclear cells expressed alpha-smooth muscle actin (4/6), desmin (1/6), S-100 (4/6), LCA (2/6) and CD68 (6/6). However, mononuclear cells were also positive for epithelial markers in 4/6 tumors (cytokeratins AE-1/AE-3, Cam 5.2, CK7 and/or EMA). p53 stained mononuclear tumor cells in three cases, paralleling the staining on the accompanying urothelial carcinoma. Ki-67 stained mononuclear tumor cells, but not osteoclast-like giant cells. Follow-up data were available in five cases. One patient developed recurrence of noninvasive urothelial carcinoma and is still alive. Four patients were dead due to disease within 15 months, three with distant metastases. The intimate association of these tumors with urothelial carcinoma along with their immunohistochemical profile supports an epithelial origin for the mononuclear cells and non-neoplastic reactive histiocytic lineage for the osteoclast-like giant cells.
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PMID:Osteoclast-rich undifferentiated carcinomas of the urinary tract. 1632 50

Perivascular neoplasms comprise traditionally glomus tumor and hemangiopericytoma (HPC). Whereas glomus tumor represents a well-defined entity, the existence of HPC as a separate entity has been questioned because a number of neoplasms of different lines of differentiation are characterized by a HPC-like vascular growth pattern. Myopericytoma represents a recently delineated entity showing a HPC-like vascular pattern. A large series of myopericytoma of skin and soft tissues has been analyzed to further characterize the clinicopathologic spectrum of this entity. Fifty-four cases of myopericytoma of skin and soft tissues were retrieved and the histology reviewed. Immunohistochemical stainings using alpha-smooth muscle actin (ASMA), desmin, and h-caldesmon antibodies were performed, and clinical data and follow-up information were obtained from referring pathologists. Thirty-four patients were male and 18 were female (gender was unknown in 2 cases). Patient age ranged from 13 to 87 years (median, 52 years). The lower extremities were most commonly affected (26 cases) followed by the upper extremities (16 cases), the head and neck region (4 cases), and the trunk (2 cases); exact location was unknown in 5 cases. In 20 cases, the neoplasms were confined to the dermis, in 6 cases an extension into the subcutis was seen, and 24 as well as 4 cases arose in subcutaneous and deep soft tissue, respectively. Two cases were multicentric; and in 1 of these patients, multiple anatomic regions were involved. Histologically, in all cases, numerous thin-walled vessels and a concentric, perivascular arrangement of ovoid, plump spindled to round myoid tumor cells was seen. However, a broad morphologic spectrum ranging from hypocellular, fibroma-like (3 cases), myofibroma-like (2 cases), angioleiomyoma-like (12 cases), and HPC-like neoplasms (13 cases) to classic myopericytomas (14 cases) and immature, cellular lesions (2 cases) was noted. In addition, 2 neoplasms with focal glomoid features, 5 intravascular, and 1 malignant myopericytomas were found. Prominent cytologic atypia and increased proliferative activity (>3 mitoses/10 high power fields) was seen in 4 and 2 cases, respectively. Immunohistochemically, all cases tested stained positively for ASMA. In addition, 29 of 32 cases tested stained positively for h-caldesmon, whereas desmin was only focally positive in 3 of 33 cases. Follow-up information was available in 46 cases (range, 7-168 months; median, 48 months). Despite marginal or incomplete excision in 23 of 46 cases, only 2 neoplasms (1 malignant and 1 intravascular myopericytoma) recurred locally (within 1 and 4 years, respectively). Despite overlapping morphologic features to angioleiomyoma and myofibroma, myopericytoma represents a distinct perivascular, myoid neoplasm of skin and soft tissues, characterized by a broad morphologic spectrum of concentrically, perivascularly growing myoid tumor cells that stain positively for ASMA and often for h-caldesmon, whereas desmin is usually negative. Most cases of myopericytoma behave in a benign fashion, but local recurrences and rarely metastases may occur in atypical and malignant neoplasms.
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PMID:Myopericytoma of skin and soft tissues: clinicopathologic and immunohistochemical study of 54 cases. 1633 Sep 49

Recent data have expanded the concept that cancer-associated stromal fibroblasts (CAFs) play an important role in tumor invasion and angiogenesis. Here, we show that platelet-derived growth factor (PDGF) is a mitogen for human CAFs isolated from hepatic metastases of colorectal cancer. The tyrosine kinase inhibitor imatinib mesylate (1 microM) abrogated the PDGF-induced DNA synthesis, and furthermore counteracted an inhibitory effect of PDGF on the expression of alpha-smooth muscle actin (alpha-SMA). High-dose imatinib mesylate (10 microM) decreased the viability of CAFs in vitro independent from co-stimulation with PDGF. Interestingly, imatinib mesylate (10 microM) strikingly induced the expression of the pro-inflammatory and pro-angiogenic cytokines interleukin (IL)-6 and IL-8, and mildly stimulated the release of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Our results suggest that imatinib mesylate, due to its anti-proliferative activity, may be effective in combination with other substances for the treatment of colorectal metastasis progression.
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PMID:Imatinib mesylate inhibits proliferation and modulates cytokine expression of human cancer-associated stromal fibroblasts from colorectal metastases. 1714 49

Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas of elderly patients and has a predilection for the limbs. Herein, we report a previously undescribed variant of MFS showing epithelioid morphology. Seventeen cases diagnosed as epithelioid MFS were retrieved from the authors' files from among 570 cases of MFS. Hematoxylin and eosin-stained sections were reexamined and immunostains for pan-keratin (15 cases), S-100 protein (15), desmin (15), and alpha-smooth muscle actin (13) were performed. Nine patients were men and 8 were women (age range 43 to 89 y; median 63.5). Fifteen patients presented with a mass, and in 2 of these there was also pain. Duration of symptoms varied from 1 to 24 months (median 3). Tumor size ranged from 2 to 15 cm (median 6.75). In 10 cases, the tumor was located in subcutaneous tissue and in 6 cases it was subfascial. The majority of the tumors were located on the limbs (8 lower extremities and 6 upper extremities) followed by neck (1), scalp (1), and trunk (1). Follow-up was available for 14 patients (range 2 to 240 mo; median 16). Twelve patients were treated by surgery followed by chemotherapy and/or radiation (8 cases). One patient received chemotherapy after an incisional biopsy and 1 patient was treated by surgery alone. Ten patients (71.4%) developed local recurrences. Seven patients (50%) developed metastases to lungs or retroperitoneum. Five patients (35.7%) have died of disease so far. Two patients were lost to follow-up. Morphologically, 14 cases were high grade, 2 were intermediate, and 1 was low grade. Tumors were characterized by a multinodular, infiltrating growth pattern with alternation of hypercellular and hypocellular myxoid areas; the latter showed prominent curvilinear vessels. Neoplastic cells were arranged singly and in small clusters in the myxoid areas or formed sheets in the hypercellular areas, where they showed epithelioid morphology with round nuclei, vesicular chromatin, prominent nucleoli, and moderate amounts of eosinophilic cytoplasm. The epithelioid areas were generally multifocal with admixed areas of conventional MFS. Immunostains were negative for all markers studied. Differential diagnosis included carcinoma, melanoma, myoepithelial carcinoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma. In conclusion, epithelioid MFS is a rare variant of MFS, accounting for <3% of MFS in consultation material. Its natural history seems more aggressive than usual high-grade MFS, with approximately 70% local recurrence and 50% metastases, even within a relatively short follow-up period.
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PMID:Epithelioid variant of myxofibrosarcoma: expanding the clinicomorphologic spectrum of myxofibrosarcoma in a series of 17 cases. 1719 25

Medullary thyroid carcinomas are aggressive neoplasias that metastasize very early to loco-regional lymph nodes, and tumors with a desmoplastic stromal reaction have a higher incidence of lymph node metastasis. In order to characterize the desmoplastic response in thyroid cancers, we evaluated the expression pattern of three molecular markers of activated fibroblasts/myofibroblasts, namely, fibroblast activation protein alpha (FAPalpha), tenascin-C (Tn-C), and alpha-smooth muscle actin (alpha-SMA), as well as the endothelial markers endoglyx-1, CD34 and CD31 in a series of 28 metastatic and non-metastatic medullary thyroid cancers. Immunohistochemical studies demonstrated that the three fibroblast activation markers (FAPalpha, Tn-C, alpha-SMA) are consistently expressed in the peritumoral and intratumoral stromal compartment of medullary thyroid carcinomas and expression of FAPalpha and Tn-C correlated with the degree of desmoplasia determined histologically (p=0.001 for FAPalpha and p<0.001 for Tn-C). Moreover, the extent of desmoplasia as well as the expression of FAPalpha and Tn-C correlated with the presence of lymph node (LN) metastases (p=0.002, p=0.005 and p=0.002, respectively). No correlation was found between the microvessel density (neoangiogenesis) in the tumor stroma, assessed with the endoglyx-1, CD34 and CD31 markers, and the degree of desmoplasia or incidence of LN metastases. Using a bioinformatics-based search of the BioExpresstrade mark database we found in a series of 48 thyroid cancers a significant correlation between FAPalpha RNA expression and incidence of LN metastases also in papillary cancers. These findings suggest that the link between specific molecular markers of tumor stromal reaction and locoregional metastasis extends from medullary to other thyroid cancer types.
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PMID:Molecular characterization of the desmoplastic tumor stroma in medullary thyroid carcinoma. 1754 5

Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic process of cancer cells. We have searched for a prognostic value of ezrin and some of its partners: alpha-smooth muscle actin and CD44H in 37 patients with an osteosarcoma. Automate immunohistochemistry (IHC) with anti-ezrin, alpha-smooth muscle actin and CD44H antibodies was performed in 66 specimens: 37 biopsies before chemotherapy, 16 resected tumours of "poor" responders and 13 metastases. The messenger RNA (mRNA) levels of ezrin of 13 frozen biopsies and 4 metastases were evaluated by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). All results were correlated to the following clinical data. Ezrin expression by IHC was found in 62% of 37 biopsies in the different histological subtypes. A good correlation was found between positive or negative samples by IHC and mRNA levels. Ezrin expression was recorded in 84.5% of metastastic samples. The mean expression of ezrin was higher in metastases than biopsies (p = 0.024). In multivariate analysis, ezrin was an independent prognostic marker for event-free survival and overall survival (OS) with p < 0.001 and p = 0.003, respectively, and alpha-smooth muscle actin for OS only (p = 0.024). Our findings suggest that ezrin and alpha-smooth muscle actin are predictive IHC prognostic markers for patients with an osteosarcoma.
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PMID:Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. 1778 74

Primary and metastatic so-called malignant fibrous histiocytoma/undifferentiated high-grade pleomorphic sarcoma (MFH) is rare in the gastrointestinal (GI) tract with approximately 50 primary and five metastatic cases reported so far. We evaluated two primary gastric and three metastatic intestinal high-grade pleomorphic sarcomas with features of storiform-pleomorphic MFH. Gastric tumours occurred in a 79-year-old man and a 68-year-old woman. One patient died post-operatively, and the other was disease-free at 6 months. Three patients presented with GI metastasis 24, 60 and 0 months after diagnosis of MFH of the heart (n = 1) and the thigh (n = 2). Metastases were located in the small (n = 1) and large bowel (n = 2) and were characteristically pedunculated and polypoid with oedematous haemorrhagic stroma. Concurrent metastases (brain, lung, bone) were present in all three cases. Tumours expressed alpha-smooth muscle actin (four of five), platelet-derived growth factor receptor (PDGFR) alpha (three of three) and PDGFRbeta (two of three) but were negative for CD117, CD34 and other lineage-specific markers. Ultrastructural examination revealed myo/fibroblastic features. Both gastric MFH were wild type for KIT and PDGFRalpha. In conclusion, primary and metastatic MFH of the GI tract commonly express PDGFRalpha and show a myo/fibroblastic phenotype. They should be distinguished from a variety of primary and metastatic pleomorphic neoplasms, in particular high-grade sarcomatous GI stromal tumours (GIST), pleomorphic leiomyosarcoma, sarcomatoid carcinoma and other mimics.
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PMID:Primary and metastatic high-grade pleomorphic sarcoma/malignant fibrous histiocytoma of the gastrointestinal tract: an approach to the differential diagnosis in a series of five cases with emphasis on myofibroblastic differentiation. 1787 30

Epithelial-myoepithelial carcinoma (EMC) of the salivary glands is an uncommon, low-grade malignant tumor. A recent report demonstrates sebaceous differentiation in this tumor even though its significance has never been documented as a precise histologic variant. Six cases of EMC exhibiting sebaceous differentiation (sebaceous EMC) of the parotid gland were analyzed for their clinicopathologic features and immunohistochemical characteristics. In addition, primary salivary sebaceous carcinomas were also examined for comparison. In our series, the incidence of sebaceous EMC was 0.2% among 3012 cases of parotid gland tumors and 14.3% of all EMC cases. The 6 patients comprised 2 men and 4 women, age ranging from 77 to 93 years (mean, 83.7 y). Neither cervical lymph node nor distant organ metastases were found in any cases of sebaceous EMC and no patients died of disease, though local recurrences developed in 1 patient. Conversely, cervical lymph node metastasis was detected in 2 of 3 patients with sebaceous carcinoma, 1 of whom died of disease at 12 months. Histologically, all 6 tumors had an area of sebaceous differentiation admixed with features of bilayered ductal structures typical of EMC. A component of sebaceous differentiation was distributed diffusely in 4 tumors and focally in 2. Cytologic atypia of sebaceous EMCs was lesser than that of sebaceous carcinomas. Immunohistochemically, putative myoepithelial markers such as alpha-smooth muscle actin, calponin, p63, cytokeratin 14, S-100 protein, and vimentin were highly expressed in sebaceous EMC. However, the expression of the latter 4 markers was also observed in primary sebaceous carcinomas, whereas these tumors were all negative for alpha-smooth muscle actin and calponin. Positive immunoreactivity for epithelial membrane antigen, adipophilin, and perilipin confirmed sebaceous differentiation in EMC. These results indicate that sebaceous EMC is a low-grade malignancy, similar to conventional EMC. Our data also suggest that immunohistochemical examination of specific myoepithelial markers is helpful in distinguishing sebaceous EMC from sebaceous carcinoma, which may occasionally be associated with an aggressive clinical course.
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PMID:Sebaceous epithelial-myoepithelial carcinoma of the salivary gland: clinicopathologic and immunohistochemical analysis of 6 cases of a new histologic variant. 1842 42


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