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)

Epithelioid sarcoma is an uncommon soft tissue malignancy which is often misdiagnosed as necrobiotic granuloma or chronic inflammation. Many patients have local recurrence and distant metastasis because of its infiltrating growth. We report a 49-year-old Japanese man who had an ulcer with surrounding erythema on the left forearm after he sustained a bruise on this spot. His mother and father had died of rectal and bladder carcinoma, respectively, and he had also had a seminoma previously. Therefore, there was familial accumulation of malignancies. A skin biopsy revealed polygonal, plump, or spindle-shaped epithelioid cells and lymphocytes infiltrating through the dermis. Immunohistochemical studies showed positive staining for cytokeratins, epithelial membrane antigen, CD34 and vimentin and negative staining for desmin, CD68, HHF-35, 1A4 and p53. These clinical and histological features were diagnostic of epithelioid sarcoma. CT scans detected nodules in the right lung. A lung biopsy revealed that he had well-differentiated adenocarcinoma which expressed p53. Mutations in the TP53 gene were not searched for. We selected conservative treatment because the patient did not want surgical wide resection or amputation. Therefore, radiation, thermotherapy, application of 0.5% doxorubicin hydrochloride ointment and right lower lobectomy with lymph node dissection were performed. The size of the ulcer and the tumor invasion along the fasciae of muscles were decreased, however, metastasis of the epithelioid sarcoma was detected in the lymph node of the left axilla four years after the diagnosis.
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PMID:Epithelioid sarcoma associated with lung adenocarcinoma. 1636 52

A 59-year-old man presented with a 10-cm x 8-cm tumoral plaque with a superficial nodule in the interscapular region of the back (Fig. 1). The lesion had been growing for 25 years. As a cystic lesion was suspected, the superficial nodule was biopsied. The histopathologic diagnosis was low-grade sarcoma with sclerosis. Two months after the initial biopsy, the lesion was completely excised, reaching the muscular fascia, with a 2-cm margin and with a free graft. Formalin-fixed paraffin-embedded samples were submitted to histologic and immunohistochemical study (4-microm paraffin sections); frozen tissue was submitted to electron microscopy. For histopathology, sections were stained with hematoxylin and eosin. Immunohistochemistry was performed following standard avidin-biotin immunoperoxidase procedures with primary antibodies for vimentin, CD34, smooth muscle-specific actin, bcl-2, S-100, desmin, myoglobin, factor VIII, p53 (all from DAKO, Copenhagen, Denmark), HHF-35 (Enzo Diagnostics, Farmingdale NY), cytokeratin (AE1/AE3) (Biogenex, San Ramon, CA), and factor XIIIa (Calbiochem Novabiochem Corporation, La Jolla, CA). At low magnification, the histologic study of the initial tumoral nodule revealed a poorly circumscribed mesenchymal proliferation, with fibroblastic-like neoplastic cells arranged in a fascicular and storiform pattern, admixed with extensive areas of sclerosis. At higher magnification, tumoral cells were spindle-shaped with hyperchromatic nuclei and scant cytoplasm. In some areas, sclerosis was so evident that a keloid-like pattern was seen (Fig. 2a). The surgical specimen showed a fibroblastic neoplastic proliferation infiltrating the dermis and hypodermis. In the dermis, cells were arranged in a storiform pattern, whereas in the hypodermis there was a honeycomb or lace-like pattern (Fig. 2b). There were also cellular areas alternating with sclerotic areas, with transitional zones in between, in both the dermis and hypodermis. The immunohistochemical study of the initial tumoral nodule and the surgical specimen showed that tumoral cells expressed vimentin, CD34 (Fig. 3), bcl-2, HHF-35, and smooth muscle actin. Neoplastic cells failed to show positivity with desmin, myoglobin, factor XIIIa, factor VIII, S-100, cytokeratin (AE1/AE3), and p53. An ultrastructural study revealed spindle cells having an irregular contour with a well-developed granular reticulum endoplasmic (REG) system in their cytoplasm, as well as some Golgi complexes and mitochondria. Also visible was the presence of many actin filaments and some myosin condensations (Fig. 4), characteristics of a fibroblastic cell with myofibroblastic differentiation. The final histopathologic diagnosis of the surgical specimen was sclerosing dermatofibrosarcoma protuberans. Two years after surgery, the patient is alive and well.
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PMID:Sclerosing dermatofibrosarcoma protuberans (DFSP): an unusual variant with focus on the histopathologic differential diagnosis. 1642 80

Clinical, histopathologic, immunohistochemical, and genetic analyses of 2 osteoclastic giant cell tumors of the pancreas are presented. The neoplasms were composed of osteoclastic giant cells and pleomorphic cells (PCs). The tissue-specific markers gave evidence of mesenchymal nature of the osteoclastic giant cells, as well as other components of the tumor, and lacked any signs of epithelial differentiation in both patients. The nonepithelial nature of both components in the osteoclastic giant cell tumors presented may be associated with a better prognosis, which corresponds to the previous reports of similar neoplasms. A positive immunoreactivity to neuron-specific enolase was recorded in patient 2. The presence of CD68 in osteoclastic giant cells proved their histiocytic nature. Both components of the tumors showed a negative immunoreactivity to desmin and only a scattered reactivity to smooth muscle cell actin, typical markers of myofibroblastic differentiation. Mutation analysis of the tumor revealed the wild state of both p53 and K-ras oncogenes in both patients. A positive immunoreactivity for p53 in PCs of both osteoclastic giant cell tumors was recorded, whereas osteoclastic giant cells did not express this protein. The expression of p21 was recorded in osteoclastic giant cells in patient 1. The absence of Ki-67 in the osteoclastic giant cells and its expression in PCs gave evidence of a different proliferation rate of both cell populations. Different tissue-specific markers, a different proliferation rate, and a different state of oncogene activation in the osteoclastic giant cell tumors contribute to the idea that the tumor derives from a pluripotent cell that may differentiate into an array of phenotypes.
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PMID:Immunohistochemical and genetic analysis of osteoclastic giant cell tumor of the pancreas. 1662 90

Ectopic hamartomatous thymoma (EHT) is a rare benign tumor. We present a case of EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19-year-old man. The tumor consisted of spindle cells, epithelial cells, adipose cells, and a small amount of lymphocytes, as described previously. Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5% of cells were positive for MIB-1 and no cells stained for p53 and bcl-2. Recognition of EHT is important and needs to be differentiated from high-grade sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath tumor.
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PMID:Ectopic hamartomatous thymoma: a case report with immunohistochemical study and review of the literature. 1664 May 45

We have established in culture a spontaneously immortalized bovine embryonic fibroblast (BEF) cell line that has lost p53 and p16(INK4a) functions. MyoD is a muscle-specific regulator capable of inducing myogenesis in a number of cell types. When the BEF cells were transduced with MyoD they differentiated efficiently to desmin-positive myofibers in the presence of 2% horse serum and 1.7 nM insulin. The myogenic differentiation of this cell line was more rapid and obvious than that of C2C12 cells, as judged by morphological changes and expression of various muscle regulatory factors. To confirm that lack of the p53 and p16(INK4a) pathway does not prevent MyoD-mediated myogenesis, we established a cell line transformed with SV40LT (BEFV) and introduced MyoD into it. In the presence of 2% horse serum and 1.7 nM insulin, the MyoD-transduced BEFV cells differentiated like the MyoD-transduced BEFS cells, and displayed a similar pattern of expression of muscle regulatory proteins. Taken together, our results indicate that MyoD overexpression overcomes the defect in muscle differentiation associated with immortalization and cell transformation caused by the loss of p53 and Rb functions.
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PMID:Myogenic differentiation of p53- and Rb-deficient immortalized and transformed bovine fibroblasts in response to MyoD. 1668 14

Embryonal sarcoma of the liver is a rare, aggressive malignant tumor that typically occurs in children and teenagers. Microscopic features include spindle, oval, or stellate cells with poorly defined cell borders, nuclear pleomorphism and multinucleation, and variable immunoreactivity to cytokeratin, vimentin, and alpha-1-antitrypsin. Intracellular and extracellular PAS-positive, diastase-resistant hyaline globules are commonly present. The authors evaluated a panel of IHC stains to better define the pattern of immunoreactivity in this tumor. Embryonal sarcomas of the liver were identified from archival files and were immunostained with antibodies: cytokeratin AE1/3, hepatocyte, SMMS, myogenin, calponin, h-caldesmon, desmin, S100, vimentin, CD34, C-kit (CD117), CD10, ALK-1, PE10, Bcl2, p53, and Ki-67. Six cases were identified. Patient age ranged from 6 to 24 years. Tumors ranged from 10 to 20 cm and contained spindled and epithelioid areas with PAS-positive, diastase-resistant globules and atypical cells with focal multinucleation. All cases showed immunoreactivity with vimentin and five showed immunoreactivity with Bcl2. Focal immunoreactivity was seen with cytokeratin AE1/3 in three cases, CD10 in four, calponin in two, desmin in one, and p53 in four. All tumors were negative with hepatocyte, myogenin, CD34, SMMS, h-caldesmon, PE10, ALK-1, and S100. No cytoplasmic staining was seen with C-kit. The proliferation index ranged from 30% to 95%. The diagnosis of embryonal sarcoma is based on typical morphologic features in a large liver tumor occurring in a young patient. The most useful IHC stains help to exclude tumors such as hepatoblastoma, hepatocellular carcinoma, embryonal rhabdomyosarcoma, and other sarcomas.
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PMID:Immunohistochemical analysis of embryonal sarcoma of the liver. 1678 89

Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53. To investigate their possible involvement in the tumorigenesis, we generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by Cre/LoxP system on a background of p53 alteration. Electroporation of Cre expression vector in skeletal muscle tissues resulted in the generation of tumor in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53(-/-) and p53(-/+) backgrounds, respectively. The tumor histology was pleomorphic RMS with characteristic bizarre giant cells, positive for desmin and alpha-sarcomeric actin and exhibiting remarkable increase in total and phosphorylated extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild-type p53 was detected in K-rasG12V-expressed tumors of p53(-/+) mice. Early lesions 3 weeks after electroporation consisted of proliferating populations of myogenic progenitors, including stem cells positive for ScaI antigen, immature cells positive for desmin and neural cell adhesion molecule-positive myotubes. Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the development of pleomorphic RMS in adult mice, providing a useful mouse model for further detailed studies.
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PMID:Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice. 1678 89

In previous experiments, a novel tumor cell line, which was characterized by dominated F6 mutated from human mesenchymal stem cells (hMSCs), was developed. The mechanism and biological characteristics of this mutation are still unclear. In this study, the histological type of F6 cells was investigated by immunohistochemistry with specific markers: vimentin, CD117, desmin, NSE and vWF. The characteristics of proliferation and metastasis were shown by PCNA (proliferating cell nuclear antigen), and nm23 and cell cycle-related genes, such as p16, p21, p53 and pRb, were analyzed by RT-PCR and immunohistochemistry. The expression of hTRAP and BMI-1 were detected by real-time PCR and Western blotting. The activity of telomerase was analyzed by TRAP (telomerase repeat amplification protocol) assay. The results showed that multi-directional differentiation occurred in F6 cells, i.e., special markers of muscle, endothelial cell and nerve system were co-expressed in F6 cells, while hardly expressed in hMSCs. F6 cells maintained the same properties as of MSCs, such as negativity for both CD117 and vimentin. F6 cells exhibited strong positivity for PCNA and negativity for nm23. The cell cycle-related genes, such as p16, p21, p53 and pRb, were not detected in F6 cells, while the expression of hTRAP and BMI-1 was significantly higher. The activity of telomerase was also significantly higher in F6 cells than that in hMSCs. These findings indicated that multi-directional differentiation occurred during the transformation of hMSCs into F6 cells, and that the genes of cell cycle and cell senescence may also be associated with the neoplasia of adult stem cells.
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PMID:Histological type of oncogenity and expression of cell cycle genes in tumor cells from human mesenchymal stem cells. 1701 87

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

Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities. We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC. Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences). Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months. In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but none of our typical cases metastasized, although they can rarely arise contemporaneously with sarcomatoid urothelial carcinomas. For these reasons, close follow-up is warranted.
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PMID:Inflammatory myofibroblastic tumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma. 1712 5


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