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)

Inflammatory myofibroblastic tumor (IMT) is a neoplasm of intermediate biologic potential. In this study, we report a subset of IMTs with histologic atypia and/or clinical aggressiveness that were analyzed for clinicopathologic features, outcome, and immunohistochemical expression of anaplastic lymphoma kinase (ALK) and other markers to identify potential pathologic prognostic features. Fifty-nine IMTs with classic morphology (5 cases), atypical histologic features (21 cases), local recurrence (27 cases), and/or metastasis (6 cases) were studied. Immunohistochemistry was performed for ALK1 and other markers (Mib-1, c-Myc, cyclin D1, caspase 3, Bcl-2, Mcl-1, survivin, p27, CD56, p53, MDM-2) using standard techniques. The 59 IMTs had an age at diagnosis ranging from 3 weeks to 74 years (mean 13.2 y, median 11 y, 44% in the first decade). The mean tumor size was 7.8 cm. Sites included the abdomen or pelvis in 64%, lung in 22%, head and neck in 8%, and extremities in 5%. The follow-up ranged from 3 months to 11 years, with a mean of 3.6 years and a median of 3 years. Thirty-three patients had local recurrences, including 13 with multiple local recurrences and 6 patients with both local recurrences and distant metastases. Six patients died of disease, 5 with local recurrences, and 1 with distant metastases. Histologic evolution to a more pleomorphic cellular, spindled, polygonal, or round cell morphologic pattern was observed in 7 cases. Abdominal and pelvic IMTs had a recurrence rate of 85%. Recurrent and metastatic IMTs were larger, with mean diameters of 8.7 and 11 cm, respectively. Cytoplasmic ALK reactivity was seen in 56%. ALK-negative IMTs occurred in older patients (mean age 20.1) years and had greater nuclear pleomorphism, atypia, and atypical mitoses. All 6 metastatic IMTs were ALK-negative. Nuclear expression of p53 was detected in 80% of IMTs overall, but in only 25% of the metastatic subset. There were no significant differences among the subgroups for c-Myc, cyclin D1, MDM-2, Mcl-1, Bcl-2, CD56, p27, caspase 3, or survivin expression. In conclusion, among these 59 IMTs, ALK reactivity was associated with local recurrence, but not distant metastasis, which was confined to ALK-negative lesions. Absent ALK expression was associated with a higher age overall, subtle histologic differences, and death from disease or distant metastases (in a younger subset). Other proliferative, apoptotic, and prognostic markers did not correlate well with morphology or outcome. Thus, ALK reactivity may be a favorable prognostic indicator in IMT and abdominopelvic IMTs recur more frequently.
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PMID:Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. 1741 97

We report 20 cases of a distinct, previously unrecognized renal neoplasm, anaplastic sarcoma of the kidney with polyphenotypic features. The tumors were identified by re-reviewing tumors with unusual anaplastic features from the National Wilms Tumor Study Pathology Center, the International Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group trials. Patients ranged in age from 10 months to 41 years (median age 5 y, mean age 12 y) and females predominated (1.5:1). Twelve tumors presented in the right kidney, and 5 in the left (laterality was unknown in 3 cases). The most common presentation was a renal mass. Grossly, most tumors were large, measured 4 to 21 cm (mean 12.7 cm) and weighed 115 to 1820 g (mean 835 g). Seven out of 12 tumors suitable for assessment had a distinct cystic component. The tumors involved the pelvi-calyceal system in 5 of the cases. Histologically, all tumors showed a spindle cell component which contained either multiple foci or diffuse, widespread anaplastic changes with bizarre pleomorphic cells and very atypical mitotic figures. Chondroid differentiation was seen in 16 cases, usually in the form of islands of hyaline cartilage (13 cases) or chondroid matrix (3 cases). The nodules of cartilage showed both benign and malignant features, often within the same tumor. In 2 cases small foci of osteoid were found whereas osteoclast-like giant cells were seen in 4 cases. Only 3 of the tumors exhibited a primitive blastema-like area. No neoplastic epithelial structures were identified. No nephrogenic rests were found. Limited immunohistochemical studies showed vimentin positivity in 5/5 cases, desmin was positive in 4/6 cases, MYF4 showed focal weak nuclear positivity in 1/4 cases, but MyoD1 was negative in all cases (0/5). PGP9.5 was focally, strongly positive in 4/5 cases and p53 was strongly positive in 3/6 cases. Cytokeratin, using the antibody CAM5.2, was uniformly negative within the tumor cells. Finally, CD56 was focally positive in 1/6 tumors, whereas all other markers were negative including NB84a (4/4), CD34 (5/6), CD99 (5/5), and WT1 (6/6 cases). In 4 tumors reverse transcriptase-polymerase chain reaction was performed to detect the SYT-SSX fusion transcript produced by the t(x;18), and the ETV6-NTRK3 fusion transcript using RNA extracted from archived paraffin blocks-results were negative in all 4 specimens. Tumor stage was known in 15 patients including 7 stage I, 4 stage II, 3 stage III, and 1 stage IV tumors. They were usually diagnosed as anaplastic Wilms tumors and treated accordingly. Of the 13 patients with a minimum of 2 years follow-up, 4 patients developed distant metastases and 1 had local recurrence including 1 patient with stage IV, 2 with stage III, and 2 with stage I at presentation. Three of them died and 2 were lost to follow-up. One patient with stage I tumor developed widespread metastases and died. Another stage I patient developed local recurrence after 3 months of diagnosis, but was lost to follow-up. Five stage I patients were alive and free of tumor at last follow-up. The most common sites of metastases were lung (3 cases), and liver and bones (2 cases each). These tumors showed pathologic features similar to the pleuropulmonary blastoma of childhood and undifferentiated (embryonal) sarcoma of the liver. In the differential diagnosis, anaplastic Wilms tumor, primary renal synovial sarcoma, malignant mesenchymoma, ectomesenchymoma, and mesenchymal chondrosarcomas have been considered but none of these tumors shared the same features as the 20 cases described here which represent a distinct clinicopathologic entity with morphologic features of a polyphenotypic anaplastic sarcoma of the kidney. Further molecular studies are needed to better understand its nature and more accurate classification.
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PMID:Anaplastic sarcoma of the kidney: a clinicopathologic study of 20 cases of a new entity with polyphenotypic features. 1789 46

Primary pure small cell carcinoma of the urinary bladder is an extremely rare and highly aggressive tumor with an average five-year survival rate of less than 10% as cited by multiple case reports. It accounts for about 0.5-1% of all bladder tumors. We present the case of a 44-years-old man, smoker (10 cigarettes/day) hospitalized in the Department of Urology, from the "Prof. dr. Th. Burghele" Hospital, Bucharest, for one month intermittent hematuria. Ultrasonography showed a sessile tumoral mass, sized 37/30mm. Transurethral resection of the tumor mass was performed and tissue fragments were sent to the pathologic lab to establish the histologic type, the degree of differentiation and invasion. Fragments of the tumor were fixed in 10% formaldehyde, paraffin embedded and processed as standard technique; the sections were stained with HE, VG and immunohistochemically with: CROMO, EMA, NSE, CD56, NK1, p53 and betaHCG. The microscopic examination reveled a tumor proliferation composed of two distinct components: extensive small cells areas and foci of typical low grade (G2) papillary urothelial carcinoma. The small cell are uniformly, round, with increased nucleo-cytoplasmic ratio, eosinophyl cytoplasm, hyperchromatic nuclei, finely granular chromatin and inconspicuous nucleoli. Immunohistochemical stains showed diffuse positive staining of the small cell component for CROMO, EMA, NSE, CD56, NK1 and urothelial carcinoma component stained focally for betaHCG. The rate of cell proliferation was increased (p53 - 80% positive reaction). Conclusions. A diagnosis of small cell carcinoma coexisting with low-grade urothelial carcinoma was established. Because of aggressive behavior and distinct treatment, the pathologist should watch out for the presence of small cell carcinoma component.
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PMID:Small cell carcinoma of the urinary bladder--a new case report. 1791 2

As patients with multiple myeloma (MM) have a variable clinical course, predictive markers would help determine the appropriate treatment strategy. Clinical staging is commonly used to predict outcome, but tumour marker expression and the underlying genetic changes are increasingly used to assess the biological aggressiveness of the disease. Recent studies have demonstrated the utility of immunohistochemistry in detecting prognostic markers, including fibroblast growth factor receptor 3, cyclin D1, c-maf and p53, which have been associated with various genetic aberrations, including t(4;14), t(11;14), t(14;16) and del(17p). While t(4;14), t(14;16) and del (17p) have been documented to confer a poor prognosis, t(11;14) appears to be a neutral or even favourable factor in some studies. CD56, CD33, CD20 and CXCR4 are promising surface markers due to their roles in MM progression, but further studies of larger cohorts are necessary to assess their prognostic relevance. In this review, the biological function and clinical relevance of the main prognostic markers in MM is discussed, and also the role of immunohistochemistry in the stratification of patients into appropriate risk categories.
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PMID:Genomic aberrations and immunohistochemical markers as prognostic indicators in multiple myeloma. 1807 70

We present the surgical and pathological findings and follow-up of 5 women diagnosed with combined endometrioid and high-grade neuroendocrine carcinoma of large cell type (LCNEC) arising in the endometrium. The mean age of the women was 75 years (range, 50-88 years). Of the 5 tumors, 4 formed polypoid endometrial masses associated with extensive lymphovascular involvement of the myometrium by neoplastic cells. A single endometrial tumor was formed by LCNEC alone, and 4 tumors were composite with varying proportions formed by endometrioid (4/5) and small cell neuroendocrine carcinoma (1/5). In all 5 LCNEC tumor components, an insular growth pattern was noted, whereas a diffuse (solid) pattern was found in 4 tumors, a trabecular in 2, and rosettes/pseudorosettes in another 2. In all 5 tumors, the LCNEC tumor components were labeled with neuron-specific enolase (NSE). Four tumors were reactive for chromogranin A, CAM 5.2, and p53. Three tumors were labeled for AE1/AE3, CD56 (NCAM), p16, and cytokeratin 7. Synaptophysin was reactive in 2 tumors, and CD117 was found in only a single tumor. Of the 3 endometrioid tumor components examined, all were reactive for NSE. Two tumors were reactive for p16 and p53, 1 for CD56, but none for synaptophysin orchromogranin A. We conclude that LCNEC of the endometrium is a distinct clinicopathological entity with a poor prognosis irrespective of stage. The gross and histomorphological features are often suggestive, but confirmation requires immunoperoxidases, including NSE, synaptophysin, chromogranin A, p16, and p53. Combined endometrioid and high-grade LCNEC possess more characteristics of a type II than a type I endometrial carcinoma.
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PMID:Combined large cell neuroendocrine and endometrioid carcinoma of the endometrium. 1815 75

Degeneration of the thymus and severe contraction of the T cell repertoire with aging suggest that immune homeostasis in old age could be mediated by distinct effectors. Therefore, receptors expressed on T cells as they undergo senescence in vitro, as well as those displayed by circulating T cells during normal chronologic aging, were examined. Monitoring of T cells driven to senescence showed de novo induction of CD56, the prototypic receptor of NK cells. Analysis of fresh T cells in peripheral blood showed an age-dependent induction of CD56. These unusual T cells expressed high levels of Bcl2, p16, and p53, and had limited, or completely lost, ability to undergo cell division, properties consistent with senescence. CD56 cross-linking without TCR ligation on CD56(+) T cells resulted in extensive protein phosphorylation, NF-kappaB activation, and Bax down-regulation. CD56 cross-linking was also sufficient to drive production of various humoral factors. These data suggest that the immunologic environment in old age is functionally distinct, rather than being a dysfunctional version of that seen at a young age. CD56(+) T cells are unique effectors capable of mediating TCR-independent immune cascades that could be harnessed to enhance protective immunity in the elderly.
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PMID:Induction of CD56 and TCR-independent activation of T cells with aging. 1820 97

We present a 6-year-old child with intraocular and extraocular mass and high intraocular pressure. The tumor mass involved a disorganized anterior segment and extended through the medial cornea and sclera. A preliminary diagnosis of retinoblastoma with extraocular extension was made. An exenteration of the left globe and orbital tissue was performed. Histological examination showed that the lesion, which occupied the posterior chamber, involved the ciliary body, extending into the iris, sclera and cornea, projecting beyond the cornea anteriorly and extending to the retina posteriorly. The tumor cells were diffusely immunoreactive to vimentin, neuron specific enolase and CD 138. The medulloepithelioma cells were focally positive to cytokeratin (AE1/AE3), cytokeratin 18, CD56,CD57, S100, HMB-45 and bcl2 while areas of retinoblastic differentiation showed diffuse immunoreactivity to synaptophysin, neurofilament and CD138 with focal immunoreactivity to calretinin. All tumor cells showed no immunoreactivity to cytokeratin 7, cytokeratin 20, epithelial membrane antigen, carcinoembryonic antigen, desmin, GFAP, and chromogranin. Nuclear staining for P53 was seen in 80% of tumor cells. The ki-67 index was 90%. The tumor was described as malignant intraocular non-teratoid medulloepithelioma with retinoblastic differentiation arising from the ciliary body. Tumor satellites were seen in the adjacent periocular soft tissue. The treatment involved exenteration of the left globe and orbital tissue with secondary skin graft following chemotherapy. The patient is well and has no recurrence after 1 year of treatment. We report that medulloepithelioma can present as a case of infantile glaucoma, can show signs of intraocular calcifications and can show retinoblastic differentiation.
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PMID:Malignant non-teratoid medulloepithelioma of ciliary body with retinoblastic differentiation: a case report and review of literature. 1841 Feb 70

Tissue microarray technology and immunohistochemical techniques have become a routine and indispensable tool for current anatomical pathology diagnosis. However, manual quantification by eye is relatively slow and subjective, and the use of digital image analysis software to extract information of immunostained specimens is an area of ongoing research, especially when the immunohistochemical signals have different localization in the cells (nuclear, membrane, cytoplasm). To minimize critical aspects of manual quantitative data acquisition, we generated semi-automated image-processing steps for the quantification of individual stained cells with immunohistochemical staining of different subcellular location. The precision of these macros was evaluated in 196 digital colour images of different Hodgkin lymphoma biopsies stained for different nuclear (Ki67, p53), cytoplasmic (TIA-1, CD68) and membrane markers (CD4, CD8, CD56, HLA-Dr). Semi-automated counts were compared to those obtained manually by three separate observers. Paired t-tests demonstrated significant differences between intra- and inter-observer measurements, with more substantial variability when the cellular density of the digital images was > 100 positive cells/image. Overall, variability was more pronounced for intra-observer than for inter-observer comparisons, especially for cytoplasmic and membrane staining patterns (P < 0.0001 and P = 0.050). The comparison between the semi-automated and manual microscopic measurement methods indicates significantly lower variability in the results yielded by the former method. Our semi-automated computerized method eliminates the major causes of observer variability and may be considered a valid alternative to manual microscopic quantification for diagnostic, prognostic and therapeutic purposes.
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PMID:Quantification of diverse subcellular immunohistochemical markers with clinicobiological relevancies: validation of a new computer-assisted image analysis procedure. 1851 May 12

Small cell carcinoma of the urinary bladder is a rare entity known as an aggressive tumor. As it is rarely associated with transitional cell carcinoma in situ but more commonly with invasive transitional cell carcinoma, its origin is not well understood. We report a case of small cell carcinoma with coexisting transitional cell carcinoma in situ, where histologic mapping and parallel immunohistochemical and molecular analyses (TP53 mutation analyses, loss of heterozygosity) were performed. Immunohistochemical characterization (synaptophysin, thyroid transcription factor-1, chromogranin A, neuron specific enolase, CD56, CK, CK7, CK20, CD44v6, and p53) emphasized the morphology. Identical point mutations of TP53 were identified in invasive small cell carcinoma and transitional cell carcinoma in situ. No loss of heterozygosity of microsatellite markers D3S3050, D9S303, D9S304, D9S171, D9S775, D9S1748, D9S1751, D17S786, D17S918, and TP53alu was found in either component. We provide, for the first time, molecular evidence for the development of invasive small cell carcinoma out of transitional cell carcinoma in situ.
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PMID:Insights from a whole cystectomy specimen--association of primary small cell carcinoma of the bladder with transitional cell carcinoma in situ. 1854 17

We report 5 polypoid high-grade neuroendocrine carcinomas of the uterus, 2 small cell carcinomas of the endometrium, and 3 large cell neuroendocrine carcinomas, 2 from the cervix and 1 from the endometrium. The 2 small cell carcinomas of the endometrium arose from and were confined to endometrial polyps, one of which also showed foci of endometrioid adenocarcinoma. The myometrium was free of tumor, despite extensive sampling. The 3 large cell neuroendocrine carcinomas, 2 from the cervix and 1 from the endometrium, were polypoid but did not originate in polyps. Two of these tumors infiltrated myometrium, and one did not. The age of the 5 patients ranged from 25 to 66 years (mean age, 43 years). Four patients presented with vaginal bleeding. One pregnant woman had the largest polypoid tumor discovered during a routine gynecologic examination. Tumor sizes ranged from 2.7 to 10 cm. All 5 patients were treated by radical hysterectomy and 4 received adjuvant chemotherapy. Only 2 patient had pelvic lymph node metastasis. All patients are alive and disease-free from 9 months to 7 years after treatment (mean survival, 47 months). All 5 tumors labeled with chromogranin and synaptophysin and 4 with CD56. Two small cell carcinomas and 2 large cell neuroendocrine carcinomas accumulated p53 protein. Two small cell carcinomas and 2 large cell neuroendocrine carcinomas expressed p16. Our findings suggest that stage of disease and a polypoid gross feature are the best predictors for outcome in small cell carcinomas and large cell neuroendocrine carcinomas of the uterus.
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PMID:Small cell carcinomas and large cell neuroendocrine carcinomas of the endometrium and cervix: polypoid tumors and those arising in polyps may have a favorable prognosis. 1858 Mar 10


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