Positivity For Smooth Muscle Actin Research Articles

A Histologic, Immunohistochemical and Ultrastructural Study of Fibroma, Myofibroblastoma, Leiomyoma and Hemangiopericytoma in Cattle

The immunohistochemical features of tumors from 7 Holstein cows showing fibroblastic, myofibroblastic, smooth muscle or pericytic differentiation are described. In cases 1 and 2, the tumors were characterized by neoplastic fibroblasts immunostained with vimentin alone, but some cells appeared to transiently express alpha smooth muscle actin (SMA) during tumor development. Cutaneous (case 3) and nasal (case 4) myofibroblastomas, which were characterized by SMA and fibronectin positivity, with a minority of cells showing positive reactivity for desmin, were readily distinguishable from tumors of fibroblasts, smooth muscle cells and pericytes by fibronectin staining. The same staining pattern was seen in a vulvar myofibroblastoma (case 5), which differed from a vaginal leiomyoma (case 6) coexpressing SMA and desmin in nearly all neoplastic cells. Both neoplasms, however, had estrogen receptor (ER), and may be derived from immature stromal cells distributed in the vulvovaginal region. A hemangiopericytoma (case 7) resembled myofibroblastomas in cytoskeletal immunophenotypes, but lacked fibronectin. Benign or locally invasive soft tissue tumors with spindle cell morphology and expression of SMA could be divided into several types by immunostaining for SMA, desmin, fibronectin and BR.

Expression of interleukin-6 and monocyte chemoattractant protein-1 by peritoneal sub-mesothelial cells during abdominal operations.

Cytokines and chemokines including interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) are secreted in response to major abdominal operations. The aim of this study was to identify the peritoneal cells that produce IL-6 and MCP-1. Samples of peritoneal tissue were taken from patients at the beginning and end of major abdominal operations. The samples were incubated in culture medium on microtitre plates for 5 h. The concentrations of IL-6 and MCP-1 were measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). In paraffin sections, cells that expressed IL-6 or MCP-1 were identified by combined in situ hybridization and immunohistochemistry. Antibodies against CD68, CD34, actin, and calretinin were included in these experiments. The median production of IL-6 increased significantly from 6256 pg/ml at the start of the operation to 20,000 pg/ml at the end. Production of MCP-1 rose from 7700 pg/ml to 11,820 pg/ml. IL-6 mRNA was mainly confined to endothelial cells. MCP-1 was expressed by a broader range of cells, consisting of actin-positive smooth muscle cells and endothelial cells, fibroblast-like cells, as well as occasional macrophages and mesothelial cells. Peritoneal endothelial cells contribute to the transient increase in concentrations of IL-6 in the circulation after surgical trauma. Recruitment of monocytes to the site of the trauma seems to be mainly effected by actin-positive smooth muscle cells and endothelial cells.

SCLEROSING STROMAL TUMOR OF THE OVARY: A CASE REPORT

Sclerozing stromal tumor of the ovary is an extremely rare neoplasm occurring predominantly in the second and third decades of life. Most patients have menstrual irregularities and pelvic pain. Infertility and endometrial pathology have also been described. A 34-year-old woman presented with hirsutism and oligomenorrhea of three months duration. Ultrasound examination showed a heterogeneous right ovarian tumor consisting of predominantly solid tissue with several loculated cysts. On T2-weighted pelvic MR images, signal intensities of the cystic components were high and those of the solid components were heterogeneous, ranging from intermediate-high to high. Dynamic MRI marked early enhancement of solid components in the right ovary. The specimen obtained from endometrial curettage showed proliferative endometrium. Preoperative serum levels of tumor markers were in normal range: preoperative serum levels of testosterone (T) (2.42 ng/ml; normal for adult females 0.1-0.8 ng/ml) and dehydroepiandrosterone-sulphate (DHEA-S) (232.4 microg/dL; normal for adult female, 35-430 microg/dL) were measured and the T value was found increased. At laparotomy, a left ovarian mass was found attached to the right infundibulopelvic ligament and a left oophorectomy was performed. The mass was described as benign by frozen analysis. Definitive histopathological diagnosis was sclerozing stromal tumor of the ovary (SST). The histologic features included a pseudolobular pattern with focal areas of sclerosis and a two-cell population of spindled and polygonal cells. Immunohistochemical studies showed positive smooth muscle actin and negative cytokeratin, keratin, S100 and desmin. The T value decreased postoperatively (0.57 ng/ml).

Intravascular radiation accelerates atherosclerotic lesion formation of hypercholesteremic rabbits

Objectives: The purpose of the present study is to evaluate the effect of intravascular radiation (IR) on the arterial wall of uninjured vessels in the hypercholesteremic rabbit model. Methods: Aortas of 24 New Zealand white rabbits were treated with either intravascular 192-Ir γ-radiation (15 Gy at 2 mm from the center of the source) or were exposed to the source catheter without radiation (sham controls). Following the radiation treatment, the animals were fed a 2% cholesterol diet until euthanasia at 2 ( n=8) or 6 ( n=16) weeks. Arteries were analyzed using light and scanning electron microscopy (SEM); transforming growth factor β (TGF-β) 1, a promoter of connective tissue deposition, was also monitored. Results: At 2 weeks, SEM analysis showed well-aligned endothelial cells in nonradiated segments, whereas irradiated arteries consistently contained adherent and subendothelial macrophages with focal areas of endothelial disruption. Further radiated segments at 2 weeks showed a 7-fold increase in active TGF β-1 over nonradiated segments. At 6 weeks, there was a significant increase in plaque and vessel wall area relative to control arteries, however, no differences were noted in the density of actin-positive smooth muscle cells (SMCs) or macrophages. Similarly, no differences were noted in cell proliferation between groups as evidenced by the marker bromodeoxyuridine (BrdU). In contrast, nonirradiated segments frequently contained cellular areas with extracellular lipid. Conclusion: Exposure of previously uninjured vessels to IR and hypercholesterolemia is associated with increased plaque burden and leads to more advanced plaque types. Special care should be taken to minimize radiation exposure in normal vascular segments in hypercholesterolemic patients undergoing radiation therapy.

平滑筋肉腫（皮膚型）の１例

Leiomyosarcomas, occurre in middle age and most common on the extremities, develop as solitary painful or tender intra-or subcutaneous nodules showing a relatively benign biologic course. We reported a 39-y-old female with intracutaneous leiomyosarcoma seen in the left inguinal region. She was in good health. First total resection was done under the diagnosis of infectious atheroma because of painful subcutaneous nodule, but histopathological feature showed that tumor nest consist of a poorly delineated proliferation of spindle-shaped atypical myomatous cells arranged in interlacing fascicle with positive smooth muscle actin stain. Wide local excision was carried out after the diagnosis. No recurrence was noted one year after the excision. [Skin Cancer (Japan) 2001; 16: 128-131]

Cytogenetic abnormalities of alveolar soft-part sarcomas using interphase fluorescent in situ hybridization: trisomy for chromosome 7 and monosomy for chromosomes 8 and 18 seem to be characteristic of the tumor.

Four alveolar soft-part sarcomas were investigated by means of standard immunohistochemistry and interphase cytogenetics to further characterize the immunophenotype and proliferative activity of this tumor. The main goal of this study was to explore the chromosomal changes of this rare soft-tissue sarcoma. One epithelial (KLI), three neurogenic [neuron specific enolase (NSE), PGP 9.5, and S100], and five myogenic (desmin, myoglobin, alpha-smooth mnuscle actin, alpha-sarcomeric actin, and MyoD1) markers were used for the immunophenotypical analysis. Proliferative activity was assessed using the Ki67 index. Twelve (peri)centromeric (1, 3, 4, 6, 7, 8, 10, 12, 15, 17, 18, and X) and one telomeric (17q25-qtel.) chromosomal probes were used for interphase cytogenetic analysis. Three of the cases showed cytoplasmic desmin and/or myoglobin, and one showed smooth muscle actin positivity. All of the four tumors had granular, cytoplasmic, possibly nonspecific MyoD1 and sarcomeric actin positivity. Two of the tumors were positive for vimentin, four gave focal and weak staining with neurogenic markers (four of four NSE, one of four S100, and four of four PGP 9.5), but none of them was positive with KLI. Alveolar soft-part sarcomas may show myogenic immunophenotype in a number of cases, which supports myogenic differentiation. Fluorescent in situ hybridization using alpha satellite chromosomal probes revealed significant alterations in all of the cases. Most frequent and repeated numerical changes, which seem to be characteristic of the neoplasm and may play an important part in its pathogenesis and/or progression, were trisomy 7, monosomy 8 and monosomy 18.

Mesenchymal Chondrosarcoma: A Small Cell Neoplasm with Polyphenotypic Differentiation.

We analyzed the clinicoradiographic, microscopic, and immunophenotypic features of 21 tumors from 13 patients with mesenchymal chondrosarcoma (11 primary and 10 metastatic) and addressed the issue of their potential polyphenotypic differentiation. The immunophenotypic profile of the tumors was analyzed by studying the expressions of the MIC2 gene protein (p30/32(MIC2)), S-100 protein, desmin, myoD1, myogenin, myoglobin, smooth-muscle actin, cytokeratin, neuron-specific enolase, and HMB-45. The expression of p30/32(MIC2) was typically restricted to the small cell component of the mesenchymal chondrosarcoma and could be documented in 17 tumors. The cartilaginous areas were positive for S-100 protein in 20 tumors. Scattered positivity of small cells for desmin was seen in 8 cases. In 2 primary tumors from different patients (1 intraosseous and 1 extraskeletal) a diffuse expression of desmin with focal coexpression of myoD1 was present within the small cell component of the tumor. The positivity for smooth-muscle actin was documented in 2 cases. Either the small cell or cartilaginous components were at least focally positive for neuron-specific enolase in 11 tumors. All tumors were negative for myogenin, myoglobin, cytokeratins (AE1/AE3, CAM5.2) and HMB-45. This study showed that, in addition to cartilaginous differentiation, mesenchymal chondrosarcomas may exhibit focal expression of desmin. In rare cases more diffuse rhabdomyoblastic differentiation can be seen within the small cell component of the tumor. Thus, mesenchymal chondrosarcoma is another primitive neoplasm with polyphenotypic differentiation and features that overlap those of other small cell malignances of bone and soft tissue. Int J Surg Pathol 8(4):291-301, 2000

Neonatal estrogen stimulates proliferation of periductal fibroblasts and alters the extracellular matrix composition in the rat prostate.

The purpose of this study was to examine whether changes in extracellular matrix (ECM) molecules are associated with the growth inhibition and differentiation defects of the prostate gland following neonatal exposure to estradiol. Using immunocytochemistry (ICC), laminin and collagen IV were localized to the basement membrane (BM) as well to the basal lamina of the periductal smooth muscle of the control developing prostates. In contrast, fibronectin and collagen III were localized throughout the stromal ECM. Exposure to neonatal estrogen altered the staining profile for specific ECM molecules. In the estrogenized rats, a thick layer of cells negative for laminin and collagen IV was observed adjacent to the BM. Electron microscopy and ICC for alpha-actin, fibronectin, and vimentin identified this multicellular layer of periductal cells as differentiated fibroblasts. Peripheral to these fibroblasts, actin-positive smooth muscle formed a second layer of periductal stromal cells. PCNA labeling showed that estrogen exposure increased the fibroblast proliferation. Because many periductal fibroblasts were positive for estrogen receptor alpha (ER alpha) in estrogenized rats, a direct effect of estradiol on their proliferation is suggested. Gelatinolytic gels revealed that estrogen exposure did not alter the activity of matrix metalloproteinases associated with tissue remodeling during prostate morphogenesis. However, the periductal fibroblast layer in estrogenized prostates was devoid of urokinase- and tissue-plasminogen activator, which may potentially alter the localized proteolysis involved in matrix remodeling. It is proposed that proliferation of a multicellular layer of periductal fibroblasts in estrogenized prostates results in a physical barrier that constrains branching morphogenesis and blocks paracrine communications between smooth muscle and epithelial cells which normally regulate differentiation.

Cellular Benign Fibrous Histiocytoma

We report seventy-four cases of a distinctive variant of cutaneous fibrous histiocytoma, which is often mistaken histologically for sarcoma and which carries a high local recurrence rate. These tumors appeared most commonly in young or middle-aged adults, with a predominance in men (male/female ratio 1.9:1). Anatomic distribution was wide, with cases occurring mainly in the upper limb/limb girdle (34%), lower limb/limb girdle (27%), and head and neck region (20%). Most lesions had been present for only a few months, and their sizes ranged from 0.5 cm to 2.5 cm in maximum diameter. Twelve (26%) of 46 cases with follow-up (mean duration 3 years) recurred locally, in one case twice. Distinctive histologic features were a commonly fascicular growth pattern, predominance of eosinophilic spindle cells with tapering nuclei, a moderate mitotic rate (mean three per 10 high-power fields), and frequent extension into the subcutaneous fat (33% of cases). In addition, all cases showed at least focal cytologic polymorphism (inflammatory cells, foam cells, giant cells), and 58% showed associated epidermal alterations in common with usual cutaneous fibrous histiocytomas. Nine cases (12%) showed foci of central necrosis. Immunohistochemical studies (ABC method) found only vimentin and very focal smooth muscle actin positivity. Tests for CD34, desmin, S-100, keratin, and Factor XIIIa were negative in all cases. These lesions should be distinguished from dermatofibrosarcoma protuberans and leiomyosarcoma, with which many of these cases were initially confused.

Myoepithelioma of the Lacrimal Gland

The case is described of a 23-year-old female patient presenting with unilateral proptosis, headaches, and transient epiphora. Surgery revealed an encapsulated tumour composed exclusively of spindle-shaped cells within a richly vascularised myxoid stroma. Immunohistochemical staining showed focal positivity for smooth muscle actin, vimentin, and glial fibrillary acidic protein. These combined findings are interpreted as providing evidence of a myoepithelioma, which may be regarded as a monomorphic adenoma consisting solely of myoepithelial cells. To our knowledge this is only the second report of such a tumour in the lacrimal gland.

Meningeal Myofibroblastoma

Myofibroblastoma is a recently described benign mesenchymal tumor. Only one case has been reported previously in the CNS. We report a second case of myofibroblastoma arising in the meninges in a 70-year-old woman who presented with visual changes. The histologic appearance was characterized by alternating areas of spindled and rounded cells separated by collagen and amianthoid fibers. Immunostaining demonstrated strong vimentin and focal smooth-muscle actin positivity; staining for epithelial membrane antigen, cytokeratin, S-100, desmin, myosin, glial fibrillary acidic protein, and factor VIII-related antigen was negative. Ultrastructurally, the myofibroblasts had features of both smooth-muscle cells and fibroblasts. Differentiating the benign myofibroblastoma from more aggressive meningeal sarcomas and meningeal meningiomas is important. The tumor most likely arises from myofibroblasts that probably reside in the meninges.

Muscle Differentiation and Clinicopathologic Features of Gastrointestinal Stromal Tumors

We analyzed 46 gastrointestinal stromal tumors (GISTs) using a panel of antibodies to determine the frequency of smooth muscle differentiation and the relationship of immunophenotype to histopathologic features and clinical behavior. Thirty-six GISTs were classified as benign or malignant based exclusively on clinical behavior; a 2-year minimum follow-up was required for benign lesions. GISTs were immunopositive in the following categories: vimentin 45 of 46, desmin nine of 45, muscle-specific actin (MSA) 36 of 46, alpha-smooth muscle actin (SMA) 34 of 46, chicken gizzard actin-7 zero of 38, cytokeratin two of 46, S100 protein six of 46, glial fibrillary acidic protein (GFAP) zero of 46, synaptophysin zero of 46, and chromogranin one of 46. At least one muscle marker was positive in 39 of 46 tumors. Five GISTs were MSA positive/SMA negative, and three were MSA negative/SMA positive. All desmin-positive cases reacted with MSA or SMA. Eight GISTs were positive for vimentin, MSA, SMA, and desmin, whereas seven were vimentin positive only. Compared with the latter, the former tended to be smaller, less often necrotic, and clinically benign (p less than 0.05 for each). All vimentin-positive only GISTs were malignant. Immunohistochemical features did not correlate with tumor site, cellularity, nuclear pleomorphism, or mitotic rate. Benign GISTs were less cellular than were malignant GISTs (p less than 0.05), but they did not differ statistically in degree of nuclear pleomorphism, necrosis, mitotic rate, or size. We conclude that (a) 85% of GISTs react with at least one muscle antibody; (b) immunohistochemical features are unrelated to anatomic site; (c) SMA is, in effect, as sensitive as MSA, whereas desmin is less sensitive; and (d) simultaneous vimentin, MSA, SMA, and desmin positivity correlates with a benign outcome.

Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: I. Normal development.

Myometrial development from the prenatal to adult period was examined in rats and mice 1) by histologic and immunocytochemical methods with anti-actin, -vimentin, and -laminin to assess cytodifferentiation of smooth muscle and fibroblastic cells; and 2) by morphometric procedures to assess quantitatively the expression of cellular orientation in the emerging inner circular myometrial layer. Uterine mesenchymal cells initially were uniformly vimentin-positive, undifferentiated, and randomly oriented during the late fetal period. By the early neonatal period, three mesenchymal layers became recognizable histologically, the middle one of which (prospective circular myometrium) developed distinct circular orientation and differentiated into a layer composed of actin-positive smooth muscle cells. The cells of the inner mesenchymal layer initially exhibited radial orientation. By 10 days postpartum, the outer longitudinal mesenchymal layer differentiated into bundles of smooth muscle cells representing the longitudinal myometrium. The inner mesenchymal layer remained vimentin-positive and differentiated into the randomly ordered endometrial stroma. The cells of the middle and outer mesenchymal layers that were destined to form myometrium initially expressed vimentin throughout and then coexpressed vimentin and actin, but with time vimentin staining disappeared in the maturing smooth muscle cells as they expressed actin.

Role of uterine epithelium in the development of myometrial smooth muscle cells.

To study the role of epithelial-mesenchymal interactions in myometrial development, uteri from neonatal Balb/c mice 1 to 60 days postpartum were utilized. Intact (untrypsinized) uteri, trypsinized but unseparated uteri, homotypic uterine tissue recombinants (separated-recombined), or uterine mesenchyme alone were grafted beneath the renal capsule of syngeneic female hosts and grown for 1 mo. Uterine mesenchyme from 1-day mice grafted alone produced small amounts of smooth muscle, most of which was associated with vasculature, whereas uterine mesenchyme from older donors possessing a rudimentary myometrium at the time of grafting formed intermediate amounts of myometrium (actin-positive smooth muscle bundles). In contrast, all specimens containing epithelium (intact, trypsinized, and separated-recombined) developed large amounts of myometrium. Uterine epithelia from neonatal through adult stages were equally effective in permissively inducing myometrial development in 1-day uterine mesenchyme. From these data, it is apparent that uterine epithelium plays an important promotional role in the differentiation and possibly the spatial organization of the myometrium.