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)

Three canine osteosarcoma cell lines were established from spontaneous pelvic and radial osteosarcomas. The cell populations cultured exhibited characteristics of malignancy and consisted of adherent, pleomorphic, mostly large spindle-shaped or polyhedral cells, characterised by the presence of numerous cytoplasmic granules and vacuoles. The main ultrastructural features included the presence of abundant rough endoplasmic reticulum and numerous cytoplasmic vesicles, deposit vacuoles and small cytoplasmic protrusions. Zymography showed that the cell lines produce high levels of MMP-2 and MMP-9, enzymes directly involved in crucial aspects of the metastatic process. Consistent with their osteoblastic lineage and malignant phenotype, all cell lines were immunoreactive to vimentin, osteopontin, PCNA, p53, MMP-2 and MMP-9, while they were negative for cytokeratin, desmin, SMA, Factor VIII, NSE, GFAP, Rb and p21 protein. No retroviral particles or RNA were detected ultrastructurally or with RT-PCR, although the possibility of viral involvement in osteosarcoma cannot be excluded. The new cell lines provide excellent in vitro models that may allow further studies on the pathobiology of canine osteosarcoma to be undertaken.
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PMID:Characterisation of three novel canine osteosarcoma cell lines producing high levels of matrix metalloproteinases. 1519 3

We present an unusual case of cutaneous carcinosarcoma with the epithelial component closely resembling nodular basal cell carcinoma, and the mesenchymal component composed of cells constituting extended follicular papillae. A solitary tumor was excised in an 80-year-old man. Histologic sections revealed an ulcerated, asymmetric, poorly circumscribed neoplasm composed of epithelial cells arranged in lobules with peripheral palisading or in a cribriform pattern. The epithelial cells were darkly basophilic with scant cytoplasm and round or oval nuclei with an indistinct chromatin pattern and nucleoli. Nuclei crowding and mitotic figures were observed. Some lobules contained melanin. There were no shadow cells, sebaceous or apocrine glandular differentiation. Each epithelial nodule was surrounded by multiple rows of cells with pale vesicular nuclei and scant cytoplasm. Smaller epithelial aggregations were encircled by these cells concentrically; in larger ones these cells were aligned across a broad front resembling so-called "continuous papillae". Additionally, numerous small follicular germ-like structures associated with papillae were seen. The cells composing "continuous papillae" showed nuclear pleomorphism, numerous mitotic figures including atypical ones, and nuclear crowding. At foci, the transition from the multilayered arrangement of these cells into their diffuse proliferation in the stroma was seen. There were no transitions between the epithelial and stromal component; both were intermingled as though being mutually dependent, with no areas revealing a high-grade tumor or dedifferentiation. Immunohistochemically, the epithelial cell component stained with cytokeratins. The cells of the mesenchymal component tested positive for vimentin and negative for desmin and cytokeratins. The proliferation index (Ki-67) was high in both components. There were also a high number of p53-positive cells in both compartments. We propose the term "low-grade trichoblastic carcinosarcoma" for this neoplasm. We are not aware of a similar tumor published in the English literature.
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PMID:Low-grade trichoblastic carcinosarcoma of the skin. 1524 61

Ovarian small cell carcinoma of hypercalcemic type (OSCCHT) is a rare neoplasm with an aggressive behavior, broad differential diagnosis, and unknown histogenesis. To add to knowledge concerning the possible aid of immunohistochemistry in resolving problems in differential diagnosis and to further explore whether that modality points to any specific histogenesis, we undertook an immunohistochemical study of this neoplasm. Fifteen OSCCHTs (including four of the ''large cell" variant) were stained with a range of antibodies, some of which have not been investigated previously in this neoplasm. Cases were stained with AE1/3, EMA, BerEP4, CK5/6, calretinin, WT1, chromogranin, CD56, synaptophysin, CD99, NB84, desmin, S100, CD10, alpha inhibin, TTFI, and p53. Staining was classified as 0 (negative), 1+ (<5% cells positive), 2+ (5% to 25% cells positive), 3+ (26% to 50% cells positive), or 4+ (>50% cells positive). All cases were positive with p53 (two 1+, five 3+, eight 4+), 14 of 15 cases were positive with WT1 (one 1+, thirteen 4+), 14 of 15 with CD10 (three 1+, four 2+, two 3+, five 4+), 13 of 15 with EMA (three 1+, three 2+, two 3+, five 4+), 11 of 15 with calretinin (nine 1+, one 3+, one 4+), 9 of 15 with AE1/3 (eight 1+, one 2+), 4 of 15 with CD56 (one 1+, two 2+, one 4+), 3 of 15 with BerEP4 (two 2+, one 4+), 2 of 15 with synaptophysin (two 1+), and 1 of 15 with S100 (4+). All cases were negative with CK5/6, chromogranin, CD99, NB84, desmin, alpha inhibin, and TTF1. The only noticeable difference in the immunophenotype between typical OSCCHT and the large cell variant was that there was 4 +EMA positivity in three of four cases of large cell variant compared with two of 11 cases of typical OSCCHT. OSCCHT is characteristically positive with AE1/3, EMA, CD10, calretinin, WT1, and p53. Combined EMA and WT1 positivity, the latter usually intense and diffuse, may be of diagnostic value, inasmuch as only a few of the neoplasms in the differential diagnosis are positive with both antibodies. Negative staining with CD99, desmin, NB84, alpha-inhibin, and TTF1 may aid in the cases in which primitive neuroectodermal tumor, rhabdomyosarcoma, intraabdominal desmoplastic small round cell tumor, neuroblastoma, a sex cord-stromal tumor, and metastatic pulmonary small cell carcinoma are in the differential. Calretinin positivity precludes its use in the differential with granulosa cell tumors. The results of this investigation do not settle the issue of histogenesis, which remains enigmatic. The typical age distribution, follicle formation, and calretinin positivity are consistent with a sex cord origin. On the other hand, WT1 and EMA positivity and negative staining with alpha-inhibin would be unusual in a sex cord-stromal neoplasm and can be used as an argument for a surface epithelial origin. Germ cell and neuroendocrine origins seem highly unlikely.
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PMID:An immunohistochemical analysis of ovarian small cell carcinoma of hypercalcemic type. 1538 2

We describe a series of unusual endometrioid carcinomas (ECs) of the uterine corpus characterized in significant part by cords of epithelioid cells, spindle cells, and a hyalinized stroma that sometimes formed osteoid. These features, particularly when prominent, produced an appearance strikingly different from that of conventional EC, sometimes resulting in problems in differential diagnosis, especially with a malignant mullerian mixed tumor (carcinosarcoma). The 31 patients ranged in age from 25 to 83 years (mean, 52 years). The proportion within each stage were as follows: stage Ia, 9.7%, stage Ib, 45.2%, stage Ic, 9.7%, stage IIb, 16.1%, stage IIIc 3.2%, and stage IV, 3.2%. In 4 patients (12.9%), staging information was not available. On microscopic examination, typical EC, which accounted for 10% to 90% of the tumor, was admixed in 90% of cases with cords of epithelioid or spindle cells within a hyalinized stroma. In 3 cases, the tumor contained cords of cells without a hyalinized stroma. Areas with a diffuse growth of fusiform cells suggesting endometrial stromal cells were also occasionally seen in minor amounts. Seventy percent of the tumors exhibited squamous differentiation, and in 50% of the tumors there was a background of endometrial hyperplasia. Two thirds of the tumors were grade 2 and the remainder were grade 1. Vascular space invasion was identified in seven tumors. On immunohistochemical analysis, the typical EC component was strongly positive for keratin, whereas the keratin staining was more focal and variable in the epithelial cells in the cords. Muscle markers (desmin, actin), CD10, and inhibin were negative in the latter. Overexpression of p53 was found in only 1 case. Eighty-three percent of the patients were alive with no evidence of disease on follow-up (range, 2-115 months; mean, 34.4 months). The clinical features, including a typically low stage and generally good prognosis, and histologic findings are different from those of malignant mullerian mixed tumors that are characterized by both high-grade carcinomatous and sarcomatous components and an aggressive clinical course. Confusion with other neoplasms, particularly those with sex cord-like growth, such as uterine tumors resembling ovarian sex cord tumors and epithelioid smooth muscle tumors, may also arise. We refer to tumors with the features described herein as "corded and hyalinized endometrioid carcinomas," a designation that reflects their two most striking and consistent features. Corded and hyalinized endometrioid carcinomas are yet another example of the protean phenotype of endometrioid adenocarcinomas of the female genital tract that has been appreciated only in the last two decades.
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PMID:Endometrioid carcinomas of the uterine corpus with sex cord-like formations, hyalinization, and other unusual morphologic features: a report of 31 cases of a neoplasm that may be confused with carcinosarcoma and other uterine neoplasms. 1564 72

Inflammatory myofibroblastic tumor (IMT) is a controversial lesion composed of myofibroblasts, accompanied by varying numbers of inflammatory cells. Various pathogenetic factors have been proposed (ie, reactive, infectious, autoimmune, and neoplastic) but the etiology of most IMTs remains unknown. Here we review the literature of oral IMTs, detailing the demographic profile of these rare lesions. Moreover, we present an unusual case of IMT arising from the mandibular alveolar mucosa of an 82-year-old female. Microscopic examination revealed plump spindle cells set in a myxoid vascular stroma admixed with inflammatory cells. Numerous large ganglion cell-like cells were seen, some exhibiting emperipolesis of neutrophils. Ultrastructurally, prominent myofibroblasts with abundant rough endoplasmic reticulum were noted. Tumor cells were immunoreactive for vimentin, smooth muscle actin, and KP1 (CD68), and negative for desmin, S-100, and EBV-LMP. The lesion was excised without margins and the patient has manifested no evidence of disease at an 18-month recall. In an attempt to further delineate the potential neoplastic nature of this lesion, we assessed the immunohistochemical expression of various markers that have been linked to neoplastic transformation. The recorded positivity for ALK, p53, MDM2, CDK4, pRb, and Ki-67, despite the absence of bcl-2 reactivity, strongly favors the neoplastic origin of the studied tumor.
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PMID:Oral inflammatory myofibroblastic tumor demonstrating ALK, p53, MDM2, CDK4, pRb, and Ki-67 immunoreactivity in an elderly patient. 1589 59

Mitochondrial dysfunctions are frequently reported in cancer cells, but their direct involvement in tumorigenesis remains unclear. To understand this relation, we stimulated mitochondrial activity by overexpression of the mitochondrial triiodothyronine receptor (p43) in human dermal fibroblasts. In all clones, this stimulation induced morphologic changes and cell fusion in myotube-like structures associated with the expression of several muscle-specific genes (Myf5, desmin, connectin, myosin, AchRalpha). In addition, these clones displayed all the in vivo and in vitro features of cell transformation. This phenotype was related to an increase in c-Jun and c-Fos expression and extinction of tumor suppressor gene expression (p53, p21WAF1, Rb3). Lastly, reactive oxygen species (ROS) production was increased in positive correlation to the stimulation of mitochondrial activity. The direct involvement of mitochondrial activity in this cell behavior was studied by adding chloramphenicol, an inhibitor of mitochondrial protein synthesis, to the culture medium. This inhibition resulted in partial restoration of the normal phenotype, with the loss of the ability to fuse, a strong decrease in muscle-specific gene expression, and potent inhibition of the transformed phenotype. However, expression of tumor suppressor genes was not restored. Similar results were obtained by using N-acetylcysteine, an inhibitor of ROS production. These data indicate that stimulation of mitochondrial activity in human dermal fibroblasts induces cell transformation through events involving ROS production.
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PMID:Stimulation of mitochondrial activity by p43 overexpression induces human dermal fibroblast transformation. 1589 20

We report a peculiar case of multifocal micronodular pneumocyte hyperplasia (MMPH) occurring in a 43-year-old man with tuberous sclerosis. Computed tomography of the chest demonstrated multiple micronodules, measuring up to 5 mm in size, present bilaterally in the lung fields, with no cystic change. Histologically, a proliferation of type II pneumocytes without the typical nulclear atypia lined the thickened alveolar septa in an adenomatoid pattern. Proliferation of immature smooth muscle cells suggestive of LAM was not observed. The characteristic findings of the positive immunohistochemical stains for cytokeratin and surfactant apoprotein A and B, and negative stains for HMB-45, alpha-1 smooth muscle actin, desmin, p53 and carcinoembryonic antigen confirmed the presence of alveolar lining cells in each MMPH lesion. Since the MMPH was observed in a male and did not appear to possess malignant potential, the MMPH appears to be a hamartomatous proliferation occurring in a male with tuberous sclerosis that is separate from lymphangiomyomatosis (LAM) which is related to estrogen and progesterone receptors.
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PMID:Multifocal micronodular pneumocyte hyperplasia in a man with tuberous sclerosis. 1594 95

Pleomorphic leiomyosarcoma (PLMS) of the adrenal gland is a rare tumor in an unusual location. A primary PLMS of the left adrenal gland is reported in a 59-yr-old Mexican woman who presented progressive flank pain and weight loss. The tumor measured 16 cm in diameter, showed markedly pleomorphic and osteoclast-like giant cells, necrosis, and high mitotic activity (average 15 per 10 high-power fields). The phenotype was supported by light microscopy and corroborated by immunohistochemistry. The neoplastic cells were strongly positive for muscle-specific actin, desmin, vimentin, and p53. They were negative for CD34, HMB45, estrogen receptors, and S-100 protein. The percentage of Ki-67 positive neoplastic cells was 7.6%. DNA content analysis by flow cytometry showed that tumor was diploid, with a high level of apoptosis. Extra-adrenal primary sites of origin were clinically excluded. The patient developed local recurrence and liver metastases 12 mo after initial treatment. She then received adjuvant chemotherapy and radiotherapy and the metastasis was resected. Twenty-four months later, she is alive with no evidence of disease. This is the second case of adrenal PLMS reported. This case exhibited a high histologic grade, aggressive behavior, and p53 overexpression, but diploid DNA content.
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PMID:Pleomorphic leiomyosarcoma of the adrenal gland with osteoclast-like giant cells. 1600 Aug 50

Sarcomatoid carcinomas are uncommon, high-grade tumors, predominantly composed of spindle cells. Only a few cases arising in the penis have been reported. The aim of this study is to better define the clinicopathologic features of this neoplasm. A total of 400 cases of squamous cell carcinoma of the penis were reviewed from which 15 sarcomatoid carcinomas (4%) were identified. Clinical and pathologic features were evaluated in all cases. Immunohistochemical studies for expression of AE1/AE3, Cam 5.2, 34betaE12, EMA, vimentin, muscle specific actin, smooth muscle actin, desmin, S-100, p63, and p53 and in situ hybridization studies for HPV were performed in 5 cases. Information about lymph node status was available in 9 cases, and follow-up in 5 cases. The mean age was 59 years, and mean tumor size was 5 cm. Grossly, most tumors were large, polypoid, and ulcerated masses frequently affecting the glans (93%) and deeply invading corpora cavernosa (80%) and skin. Microscopically, the lesions were predominantly composed of atypical spindle cells disposed in interlacing fascicles, resembling fibrosarcoma or leiomyosarcoma, sometimes admixed with pleomorphic giant cells mimicking malignant fibrous histiocytoma. One case was predominantly composed of myxoid areas. Less frequent and focal patterns were pseudoangiomatous and epithelioid. Mitotic figures were numerous, and necrosis was prominent. Foci of heterologous differentiation toward bone (osteosarcomatous component) were present in 1 case. Four cases showed a minor mixed component of usual, papillary, verrucous, and basaloid carcinoma. Intrapenile metastasis ("satellitosis") was present in 4 tumors. One of the cases was multicentric with a separate independent focus of well-differentiated carcinoma with pseudohyperplastic features. Associated low- and high-grade squamous intraepithelial lesions were noted in 73% of the cases. Immunohistochemical studies and HPV in situ hybridization were done in 5 cases. The spindle cells were diffusely positive for vimentin and p53 and showed at least intermediate expression of 34betaE12 and p63 in all cases. EMA and AE1/AE3 were focally positive in 60% of the cases, and Cam 5.2 was focally positive in 1 case. Tumor cells failed to express muscle specific actin, smooth muscle actin, desmin, and S-100. HPV in situ hybridization was negative in all cases. Inguinal metastases were present in 89% of the cases. Two of five patients with adequate follow-up died of disease within 8 months of the diagnoses. In conclusion, penile sarcomatoid carcinomas are unusual, large, and aggressive tumors usually associated with lymph node metastasis and poor outcome. Differential diagnoses include sarcoma and melanoma. Cytokeratin 34betaE12 and p63 appear to be the more specific and sensitive markers to categorize these tumors as epithelial. Diffuse immunoreactivity for p53, compared with a more basal and focal reactivity in differentiated squamous cell carcinoma, may be indicative of a late mutation in the natural progression of the disease.
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PMID:Sarcomatoid carcinoma of the penis: a clinicopathologic study of 15 cases. 1609 3

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


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