Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinicopathologic, immunohistochemical, and ultrastructural features of soft tissue angiosarcomas are not well defined. Eighty cases of angiosarcoma that involved the deep subcutis, skeletal muscle, retroperitoneum, mesentery, and mediastinum are reported. The lesions occurred in 50 male and 30 female patients who were 5-97 years of age; the peak incidence was in the seventh decade of life. A variety of associated conditions were documented in 20 of these cases, including a history of other neoplasms (some irradiated), synthetic vessel grafts, heritable conditions, and prior trauma or surgery. The angiosarcomas occurred in the extremities (n = 43 cases), trunk (n = 28), and the head and neck (n = 9) regions, with the thigh and the retroperitoneum being the most common sites. They often were characterized as enlarging, painful masses of several weeks' duration and were occasionally associated with acute hemorrhage, anemia, or a coagulopathy. The tumors measured 1-15 cm in diameter (median 5 cm) and frequently were hemorrhagic and multinodular. There was a wide morphologic spectrum within and between cases, including areas similar to cavernous and capillary hemangioma, Dabska tumor, spindle cell and epithelioid hemangioendothelioma, various spindle cell sarcomas, or carcinoma. Histologically, epithelioid angiosarcoma was the most frequently observed pattern; 70% of cases had epithelioid cells that were arranged in nests, clusters, papillae, and gaping vascular channels. Hemorrhage tended to obscure the diagnosis in several cases and often was associated with papillary endothelial hyperplasia-like areas. All 42 cases studied immunohistochemically stained at least focally for Factor VIII-related antigen, and nearly all stained strongly for vimentin, which accentuated the endothelial cells and vessel lumen formation. CD34 antigen was detected in 74% of cases, BNH9 in 72%, and cytokeratins in 35%. Epithelial membrane antigen, S-100 protein, and HMB45 were not detected. Fifty-five percent of the tumors had intracytoplasmic aggregates of laminin. Immunostains for alpha-smooth muscle actin demonstrated a prominent pericytic component in several tumors (24%). Ki67 immunostains with MIB1 indicated high proliferative activity (> or =10%) in 72% of cases. p53 immunoreactivity (>20% nuclear staining) was observed in 20% of cases. Ultrastructural studies performed on poorly differentiated areas of 12 cases showed groups of cells, which were frequently epithelioid, surrounded by basal lamina, and closely associated with pericytes, along with intercellular and intracellular lumina with or without red blood cells. Whorls of abundant intermediate filaments, occasional tonofilamentlike structures, and pinocytotic vesicles also were noted. In contrast to the findings of others, Weibel-Palade bodies were not seen. Follow-up in 49 cases (61%) showed that 53% of patients were dead of disease at a median interval of 11 months, whereas 31% had no evidence of disease at a median interval of 46 months. The remaining patients were either alive with disease (14%) or alive but disease status was unknown (2%). There were local recurrences in 20% of cases and distant metastases in 49%, most frequently to the lungs, followed by the lymph nodes, soft tissues, bone, liver, and other sites. These results indicate that angiosarcoma of soft tissue is a high-grade sarcoma. Older patient age, tumor location in the retroperitoneum, and larger tumor size as well as detection of MIB1 in > or =10% of the tumor cell population were all associated with a poorer prognosis.
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PMID:Angiosarcoma of soft tissue: a study of 80 cases. 963 Jan 75

Three cases of primary gliosarcoma (GS) were studied by immunohistochemical, ultrastructural and fluorescence in situ hybridization (FISH) methods. All tumors occurred in the supratentorial regions of the body. No patient had a prior history of irradiation to the brain. All patients died of tumor within 1 year, and autopsies were performed in two cases. Microscopically, each of the three tumors showed a mixture of glioblastoma (GBM) and a sarcomatous component (SC), which resembled fibrosarcoma with various histological features. Numerous collagen and reticulin fibers were seen in the SC of all tumors. Glial fibrillary acidic protein (GFAP) was immunoreactive only in the gliomatous component (GC). Factor VIII-related antigen was negative except for endothelial cells. One tumor exhibited alpha-smooth muscle actin positivity in the SC. Expression of MIB-1 and p53 protein was demonstrated in both components for all tumors. Labeling indices (LI) for MIB-1 ranged from 7.7 to 36.1%, and LI for p53 protein ranged from 2.9 to 57.0%. Ultrastructurally, astrocytic cells were characterized by a polygonal configuration with many cytoplasmic projections and occasional filaments. Spindle-shaped fibroblasts in the SC contained well-developed rough endoplasmic reticulum. Fluorescence in situ hybridization (FISH) performed on fresh materials or paraffin-embedded tissue demonstrated single signals for chromosome 10 in 40.6-58.3% of cells and for chromosome 17 in 37.9-48.6% of cells. Two tumors were regarded as containing losses of both chromosomes 10 and 17, while the third showed a substantial loss only of chromosome 10. As similar aberrations have been reported in GBM, these chromosomal abnormalities suggest a common pathogenesis in GS and GBM.
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PMID:Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. 973 6

Two cases of mesothelial/monocytic incidental cardiac excrescences in a 66-year-old female and an 80-year-old male are presented. Lesions had solid and tubular pattern formations which were composed of two predominant cell types of histiocytoid cells and cuboidal cells arranged in strips. The histiocytoid cells were round and had well-defined nuclei with prominent nuclear grooves. They had a low nuclear to cytoplasmic ratio. There were no atypical mitoses. Immunohistochemically, these cells were positive for leukocyte common antigen (LCA) and CD68 (KP-1) but negative for keratin. The cuboidal cells were present in strips, had haphazardly arranged surface microvilli and had small round non-cleaved nuclei. These cells were positive for keratin but negative for LCA, CD68, p53, proliferative cell nuclear antigen, alpha-smooth muscle actin, Factor VIII, epithelial membranous antigen and vimentin. These lesions are probably reactive because of their heterogeneous components; an expected feature for an essentially artifactual lesion that is related to cardiac surgery and invasive catheterization. Immunohistochemical studies are useful for avoiding misdiagnosis of neoplasms.
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PMID:Two cases of mesothelial/monocytic incidental cardiac excrescences of the heart. 973 13

Cellular and molecular events contributing to tubulointerstitial fibrosis of the kidney during obstructive nephropathy are driven in large part through increased angiotensin II levels in the obstructed kidney. Angiotensin converting enzyme inhibition or AT1 receptor antagonism have been shown to ameliorate the fibrosis of the kidney due to obstruction of the ureter. In this investigation, we determine the effects of the AT2 receptor antagonist PD-123319 on pathophysiological events within the kidneys of rats with unilateral ureteral obstruction. Treatment with PD-123319 was found to exacerbate the increase in interstitial volume and collagen IV matrix score of the ureteral obstructed kidney. Monocyte/macrophage infiltration of the injured kidney was no different between treated and untreated animals. The AT2 receptor antagonist did, however, inhibit apoptosis of tubular cells, alpha-smooth muscle actin expression within the interstitium, and p53 expression in the ureteral obstructed kidney. These results suggest that angiotensin II operating through the AT2 receptor exerts an antifibrotic effect on the kidney during obstructive nephropathy in opposition to the profibrotic effects of angiotensin II operating through the AT1 receptor.
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PMID:Effect of AT2 receptor blockade on the pathogenesis of renal fibrosis. 988 78

To investigate the development and progression of colorectal carcinoma, submucosal invasive carcinoma (SMC) with residual intramucosal neoplasm was studied histopathologically. Intramucosal neoplasm was confirmed by immunohistochemical staining against anti-alpha-smooth muscle actin antibody. Submucosal invasive carcinoma was classified into polypoid growth-type carcinoma (PGC) and non-polypoid growth-type carcinoma (NPGC), depending on the presence of intramucosal tumor proliferation. Tumors were > 15 mm in size in 78.2% of the PGC lesions studied, but the degree of submucosal invasion was minimal (invasion of the upper 500 microm of the submucosal layer) in 52.9% of the PGC lesions. Conversely, 64.4% of NPGC lesions were 15 mm in size and the degree of submucosal invasion was moderate or severe (involving the middle and deeper layer of the submucosa) for 72.9% of NPGC. In other words, lesions of NPGC were significantly smaller in size but showed deeper infiltration than PGC lesions. Furthermore, PGC was derived from intramucosal polypoid carcinoma (including carcinoma with adenoma) and was morphologically identical to polyp cancer as reported previously. However, NPGC was derived from the flat and/or depressed type of intramucosal carcinoma classified not as polyp type, but as the superficial type. Typical NPGC was, therefore, also of the superficial type. In addition, approximately 25% of PGC lesions were identified as having an adenoma-carcinoma sequence. There was no coexistence with adenoma in the NPGC lesions, suggesting de novo development. When the degree of histologic atypia in the two types of intramucosal carcinoma was compared, 74.7% of PGC lesions showed low-grade carcinoma, regardless of tumor size, while 62.7% of NPGC lesions showed high-grade carcinoma in the intramucosal lesion. Approximately 25% of carcinomas with low-grade atypia were positive for p53 (as were the high-grade lesions), but it was not expressed in the adenoma. Therefore, tumor development and the degree of invasion differed significantly between the two types of carcinoma.
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PMID:Histologic and immunohistochemical analysis of early submucosal invasive carcinoma of the colon and rectum. 1050 21

The purpose of this study was to obtain further information regarding cellular differentiation and proliferative characteristics of dedifferentiated liposarcoma (DDL) arising in the retroperitoneum and mesentery for accurate diagnosis and prognostic criteria. The patients included 20 men and 12 women, mean age, 60 years (range, 33 to 80 years). Twenty-seven tumors were located in the retroperitoneum and 5 in the mesentery. Tumor size ranged from 9 to 51 cm (mean, 24 cm). Follow-up was available on all patients and ranged from 4 to 243 months (mean, 64 months). Twenty-four (75%) patients developed local recurrences, 3 (9%) had distant metastasis, and 16 (50%) died of the disease. The predominant histology of dedifferentiation (DD) included fibrosarcoma or malignant fibrous histiocytoma (MFH) in 15 (47%), myxofibrosarcoma (myxoid MFH) in 5 (16%), mixed type in 10 (31%), and a whorling pattern in 2 (6%). Divergent differentiation, such as osseous, osteosarcomatous, chondrosarcomatous, and leiomyosarcomatous, was observed in 9 (28%). Immunoreactivity for vimentin, desmin, CD34, neurofilament, alpha-smooth muscle actin, p53, and MDM2 was observed in 32 (100%), 14 (44%), 8 (25%), 13 (41%), 14 (44%), 19 (59%), and 18 (56%) of DD areas, respectively. On the basis of a histological grading using MIB-1 (MIB-1 index range, 3% to 80%; mean, 27%) to replace mitosis counts (1 to 35/10 high-power fields [HPF]; mean, 13/10 HPF), 16 tumors each were classified as low-grade (grade 2) and high-grade (grade 3). The mixed type with poorly differentiated areas including scattered lipoblasts could be mistaken for myxoid liposarcoma but lacked the C/EBP-homologous protein-translocated in liposarcomat (CHOP-TLS) fusion genes specific for myxoid liposarcoma. Period to the first recurrence and histological grade using the MIB-1 index were associated with overall survival. Identification of DD areas, especially a poorly recognized variant of the mixed type, careful follow-up to detect early recurrence, and histological malignancy grading combined with proliferation indices are important in providing an accurate prognosis for all patients with retroperitoneal and mesenteric liposarcoma.
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PMID:Dedifferentiated liposarcoma of retroperitoneum and mesentery: varied growth patterns and histological grades--a clinicopathologic study of 32 cases. 1087 66

A prostatic smooth muscle cell line (PSMC1) was established from the dorsolateral prostate of p53 null mice. The cell line is nontumorigenic when inoculated subcutaneously, under the renal capsule or intraprostatically in syngeneic mice. These cells express alpha-smooth muscle actin (alpha-SMA), indicating their smooth muscle origin, and TGF-beta significantly enhances expression of alpha-SMA. The cells express both androgen receptor (AR) mRNA and protein, and respond mitogenically to physiological concentrations of androgens. PSMC1 cells produce significant amounts of TGF-beta, which stimulates growth by an autocrine mechanism. Dihydrotestosterone (DHT) increases proliferation of PSMC1 cells by promoting TGF-beta secretion. Considering the significant inhibitory effect of TGF-beta on prostatic epithelial cells and its stimulatory effect on the PSMC1 cells, we postulate that TGF-beta produced by prostatic smooth muscle cells may have a paracrine effect on the prostatic epithelium. We also postulate that TGF-beta may be involved in the etiology of benign prostatic hyperplasia (BPH) by stimulating excessive stromal proliferation. Line PSMC1 is the first reported androgen-responsive murine smooth muscle cell line. It will be useful for in vivo and in vitro experiments to study the mechanisms of androgen action on prostatic stroma and for delineating the interactions that occur between prostatic smooth muscle and epithelium that may lead to prostatic diseases such as BPH.
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PMID:Transforming growth factor-beta is an autocrine mitogen for a novel androgen-responsive murine prostatic smooth muscle cell line, PSMC1. 1105 12

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya's criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty-four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P = 0.001). There was no correlation between the ACD-present group and the ACD-absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c-erbB2; Ki-67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin-embedded tissue of a ACD case at 3 microm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using alpha-smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD-present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P = 0.001). All 44 ACD lesions had no staining of c-erbB2, regardless of staining in malignant lesions. The mean Ki-67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.
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PMID:Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: assessment of ACD as a precancerous lesion. 1110 51

Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma, is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report a case of myxofibrosarcoma, intermediate grade, involving the thigh along the fascial plane and between the muscles without the formation of an apparent nodular lesion. On microscopic examination, the tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern. Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34. More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was approximately 30%. Desmin, alpha-smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin, epithelial membrane antigen, bcl-2 protein and neurofilament were negative. The absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. Seven years after hindquarter amputation, the patient has been alive without evidence of local recurrence or distant metastasis. This case indicates that myxofibrosarcoma can demonstrate a highly infiltrative growth pattern. It is possible that this infiltrative nature is associated with a high rate of local recurrence of the tumor. A careful radiological examination of the extension of the tumor prior to surgery is mandatory considering the infiltrative nature of myxofibrosarcoma.
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PMID:Myxofibrosarcoma with an infiltrative growth pattern: a case report. 1118 94

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors. The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, alpha-smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis. Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and alpha-SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and alpha-SMA all showed a distinctive pattern of staining in MACs. Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.
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PMID:Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis. 1125 20


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