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)

We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice. Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week. All major salivary glands were affected, as well as a set of previously undescribed buccal accessory salivary glands located on the apex of the masseter muscle, close to the oral angle. The tumors appear to arise from the cytokeratin 5-positive basal cell compartment. Myoepithelial cells participated in the hyperplasias but not in carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas did not accumulate immunoreactive p53 but are positive for p63, as assayed by immunohistochemistry using an antibody against the N terminus of DeltaN p63, a splice variant of p63 that can inhibit p53 transcriptional activity. In this study, we provide evidence that the ras oncogene, targeted to a specifically sensitive cell compartment within the salivary glands, can trigger a series of event that are sufficient for full carcinogenesis.
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PMID:Rapid development of salivary gland carcinomas upon conditional expression of K-ras driven by the cytokeratin 5 promoter. 1665 31

It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA) in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02). Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis.
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PMID:Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers. 1680 36

Biocompatibility and cell seeding capability of a new cell scaffold made of textured polylactic acid (PLA) fibers was investigated as a new material for tissue engineering of anterior cruciate ligaments (ACL). Adhesion and proliferation of human mesenchymal progenitor cells (MPC) was investigated after 15 days by scanning electron microscopy and standard histology. Expression of collagen type I and III, fibronectin, tenascin C, decorin, smooth muscle actin, and the matrix metalloproteinases MMP-1 and MMP-2, as well as their tissue inhibitors TIMP-1 and TIMP-2 was analyzed using real-time PCR. Protein expression of collagen I and III, tenascin C, and proliferating nuclear antigen (PCNA) was determined by immunohistology. Apoptosis was analyzed by detection of p53 expression and TUNEL staining. MPC seeded the scaffold homogeneously and showed good cell growth and no increased rate of apoptosis. After 15 days, the matrix forming genes collagen type I, tenascin C, and decorin were upregulated, indicating the formation of a ligament-like matrix. MMP-1 and TIMP-1 were also significantly increased, suggesting initial matrix remodeling. It was concluded that the new porous PLA scaffold allowed homogeneous cell seeding, a fibroblastic phenotype and the production of a ligament-like matrix and, therefore, might be a suitable cell carrier for ACL tissue engineering.
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PMID:Human mesenchymal progenitor cell responses to a novel textured poly(L-lactide) scaffold for ligament tissue engineering. 1692 14

4 cases (2 males and 2 females) of mucinous tubular and spindle-cell carcinoma of the kidney were studied. The patients' age was 43 to 87 years. Microscopically, this tumor comprised two major cell populations. One of them involved spindle cells with a sparse cytoplasm, which were arranged in the fascicular pattern, often resembling low-grade smooth muscle tumors. The other population was small cuboidal cells with round nuclei and an eosinophilic cytoplasm. The mitotic activity was low. Only one tumor had both cell components. The other three tumors were represented by the second type cells. Immunohistochemical staining with avidin-biotin was performed by using cytokeratin, vimentin, SMA, p53, Bcl 2, EMA, and CD10. All cases were stained positively with antibodies to the cytokeratins AE1-AE2 and vimentin. The expression of EMA, Bcl 2, and CK7 was varying in different tumors. Responses to smooth muscle actin, p53, CK20, and CD10 were negative in all cases. Mucinous tubular and spindle-cell carcinoma of the kidney should be differentiated from angiomyolipoma with the preponderance of a leiomyomatous component, renal smooth muscle neoplasms, metanephrotic adenoma, and renal cell carcinoma with sarcomatoid differentiation.
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PMID:[Mucinous tubular and spindle-cell carcinoma of the kidney]. 1698 88

We describe a rare tumor occurring in the left pulmonary lobe of a 71-year-old Japanese man. The tumor, which was resected by left lower lobectomy, measured 65 x 50 x 50 mm. Histologic examination revealed papillary adenocarcinoma in small cell carcinoma, and chondrosarcoma. Also, the blastemal cells were located between the small cell carcinoma and the chondrosarcoma, and intermingled with both components. In blastemal cells, some glands resembled a well-differentiated fetal adenocarcinoma. The tumor was diagnosed as combined small cell carcinoma with pulmonary blastoma and papillary adenocarcinoma according to the 2004 WHO classification. Immunohistochemically, the small cell carcinoma expressed TTF-1, pancytokeratin, CD56, synaptophysin, and S100 protein, while blastemal cells expressed vimentin, desmin, smooth muscle actin, CD56, and S100 protein. To investigate whether the tumor was clonal or not, p53 gene mutation of each tumor component was analyzed by laser-captured microdissection, polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. Despite the histologic complexity, all components showed the same mutation at exon5 of the p53 gene. These results indicate that the tumor was clonal and arose from a relatively primitive cell, and that p53 mutation occurred before histologic metamorphosis or differentiation.
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PMID:Combined small cell carcinoma with pulmonary blastoma and adenocarcinoma: case report and clonality analysis. 1704 68

To further define the clinicopathologic spectrum of epithelial-myoepithelial carcinoma (EMCa), we report the gross, histologic, and immunophenotypic characteristics of 61 tumors seen within a 30-year-period. The mean age at presentation was 60.9 years, with a female predominance (1.5:1). The most common sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%), and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. However, new morphologies in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and sebaceous differentiation (13.1%) were noted. Specific histologic variants were dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%). All cytokeratin cocktails selectively highlighted the epithelial component well. Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively). p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was 36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and 10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most important univariate predictors of recurrence were margin status (log rank P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with a broader morphologic spectrum than previously thought, with several key features predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting the biphasic nature of the tumor.
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PMID:Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. 1719 18

Liposarcoma is one of the commonest soft-tissue sarcomas, but very rare in the oral cavity. We present two cases of liposarcoma of the oral cavity, together with the related clinical, histopathological and immunohistochemical findings: one affecting the cheek of a 62-year-old man and the other the gingival maxillary tuber of a 41-year-old woman. At histological examination a diagnosis of liposarcoma was made in both cases. In the first case, immunohistochemical analysis revealed intense positivity for p53, MIB-1, MDM2, and focal positivity for S100 protein and CD34, but was negative for alpharsmooth muscle actin, desmin and CD68. The second case it was intensely positive for p53, MIB-1, S-100, and focal positive for MDM2, but negative for alpha smooth muscle actin, CD34, CD68 and desmin. Histological examination and immunohistochemical profiles in the first case were consistent with pleomorphic liposarcoma, whilst that in the second case with dedifferentiated liposarcoma. Both patients were subjected to surgical treatment with wide surgical margins, without adjuvant radio- or chemotherapy. The first case was lost at follow-up one year after surgery, while the second case has not undergone relapse after seven years. We discuss differential diagnosis, examining the histopathological and immunohistochemical features that are potentially useful for distinguishing this tumor from other malignant adipose tissue tumors.
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PMID:Liposarcoma of the oral cavity--case reports of the pleomorphic and the dedifferentiated variants and a review of the literature. 1721 52

Perivascular epithelioid cell tumor (PEComa) is rare entity and has been described only recently. By immunohistochemistry and genetics it belongs to the family of tumours which comprises angiomyolipoma, clear cell "sugar" tumor of lung, lymphangioleiomyomatosis and clear cell myomelanotic tumor of ligamentum falciforme/teres hepatis. We describe an unusual case of hepatic PEComa arising in a 55-year-old woman with previous history of glioblastoma. Histologically the tumor grew in expansive way, and was composed of clear and eosinophilic epithelioid cels, without vascular or lipomatous component characteristic of angiomyolipoma. There was mild nuclear pleomorphism, sporadic mitotic activity and haemorrhage without necrosis. On immunohistochemistry, the tumor was HMB-45+50, Melan-A and smooth muscle actin positive. Tyrosinase, S-100 protein, cytokeratin coctail, EMA, vimentin, muscle specific actin, CD10, TTF-1, hepatocyte, desmin and cyclin D1 were negative. Sporadic nuclear p53 positivity was seen. The main differential diagnosis of hepatic PEComa includes clear cell variant of liver cell adenoma and hepatocellular carcinoma, metastases of various clear cell carcinomas and metastasis of malignant melanoma. In respect of uncertain biologic potential of PEComa, long term follow up is indicated.
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PMID:[Perivascular epithelioid cell tumor (PEComa) of the liver: a case report and review of the literature]. 1737 Apr 72

Inflammatory myofibroblastic tumors IMTs are clinico-pathologically distinctive but biologically controversial entities; they rarely affect the head and neck region and usually follow a benign clinical course after radical excision. We reviewed the literatures of IMTs and present a rare case of IMT arising from the maxillary paranasal sinus of an 11-year-old girl. Moreover, we elaborate on the morpho-immunophenotypic characteristics of this lesion. Microscopic examination revealed a spindle cell proliferation set in a highly vascular stroma with numerous inflammatory cells. Tumor cells were immunoreactive for vimentin, and smooth muscle actin, negative for desmin, S-100, p53, Cyclin D1, and bcl-2. The potential neoplastic nature of this lesion was substantiated by the strong diffuse immuno-expression of ALK-1 protein, a marker that has been linked to neoplastic transformation. The lesion was excised completely by a CO2 LASER as a new treatment modality and the patient manifested no evidence of disease recurrence at 10-months recall.
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PMID:Inflammatory myofibroblastic tumor of paranasal sinuses. 1745 91

Immunohistochemical techniques were used to investigate the origin of a spindle cell tumor in the anterior uveal tract of dogs and the influence of ultraviolet radiation on the development of this tumor. Thirteen tumors were identified from the 4,007 canine ocular samples examined at the Comparative Ocular Pathology Laboratory of Wisconsin between 1978 and 2005. Siberian Husky and Siberian Husky mix dogs were overrepresented (10/13 dogs, overall median age 10 years). Light microscopic evaluation (all dogs) and electron microscopy (2 dogs) were performed. Immunohistochemical staining included alpha-smooth muscle actin (SMA), vimentin, S-100, desmin, glial fibrillary acidic protein (GFAP), Melan A, microphthalmic transcription factor (MITF-1), protein gene product 9.5 (PGP 9.5), laminin, gadd45, p53, proliferating cell nuclear antigen (PCNA), anti-UVssDNA (antibody for detection of (6-4)-dipyrimidine photoproducts), and telomerase reverse transcriptase (TERT). All tumors occurred in the iris with or without ciliary body involvement and were composed of spindle cells arranged in fascicles and whorls (variable Antoni A and B behavior). All tumors were positive when immunostained for vimentin and S-100. Nine of 13 tumors exhibited GFAP immunopositivity. All tumors were negative for SMA, desmin, Melan A, and MITF-1. Tumors were variably positive for PGP 9.5, laminin, gadd45, p53, PCNA, anti-UVssDNA, and TERT. Electron microscopy revealed intermittent basal laminae between cells. These tumors are morphologically and immunohistochemically most consistent with schwannoma. The relationship between spindle cell tumors of the anterior uvea of dogs, altered neural crest, blue iris color, and ultraviolet radiation has not yet been fully elucidated.
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PMID:Uveal spindle cell tumor of blue-eyed dogs: an immunohistochemical study. 1749 Oct 68


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