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)

Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression.
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PMID:Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver. 1209 75

Nephrogenic metaplasia of the bladder and urethra has been the subject of extensive studies in recent years. However, information about ureteral involvement is still limited because of the rarity of the lesion. We described four cases of nephrogenic metaplasia of the ureter. They occurred in two men and two women whose ages ranged from 46 to 69 years. Three patients had stones, and one had multiple episodes of cystitis and chronic pyelonephritis. The lesions led to ureteral obstruction that in two patients was radiographically suspicious for carcinoma. Microscopically, three lesions were composed of tiny mucin-containing microcysts and medium-sized tubular structures lined by cuboidal cells that showed cytologic atypia characterized by enlarged vesicular nuclei and prominent nucleoli. However, there were no mitotic figures. Two lesions invaded the full thickness of the wall of the ureter and exhibited an infiltrative growth pattern highlighted by cytokeratin stains. The remaining two lesions were confined to the lamina propria. The cells of nephrogenic metaplasia were immunoreactive to cytokeratin 7 and AE1-AE3. They lacked reactivity for monoclonal and polyclonal CEA and p53. The MIB-1-labeling index was <5%. The cytologic atypia and infiltrative growth pattern of ureteral nephrogenic metaplasia should not be misinterpreted as evidence of malignancy. All four patients are alive and symptom free 8 months to 7 years after diagnosis.
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PMID:Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. 1211 15

Pure yolk sac tumor is the most common malignant gonadal tumor of infants and toddlers. However, the majority of extragonadal germ cell tumors in the midline are either seminomas (germinomas) or teratomas, and pure yolk sac tumors account for only a small fraction of these lesions. To date, only 1 primary urachal pure yolk sac tumor has been reported in the literature. We describe another case, occurring in a 7-month-old male infant who presented with a rapidly enlarging intra-abdominal tumor with marked engorgement of the superficial venous plexus around the umbilicus. With periodic follow-up for 3 years following surgical extirpation of the tumor and adjuvant chemotherapy, this patient is still alive without evidence of disease. Notably, the glandular elements predominating in the frozen sections resulted in the initial misdiagnosis of the tumor as a urachal adenocarcinoma, although the entirely resected specimen revealed typical histologic patterns and Schiller-Duval bodies. Immunohistochemistry showed that the tumor cells were diffusely reactive to alpha-fetoprotein, alpha(1)-antitrypsin, and cytokeratin. Tumor cells were negative for p53 protein, but revealed overexpression for MDM2 protein. Flow cytometry demonstrated a diploid DNA content with S-phase being as high as 55.36%. This case emphasizes that pure yolk sac tumor can occur primarily in the remnant of the urachus in young children.
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PMID:Primary yolk sac tumor of the urachus. 1220 63

The basal cell-specific cytokeratin antibody (34betaE12) is widely used to aid in the diagnosis of cancer in challenging prostate needle biopsies (NBX) and transurethral resections of the prostate (TURP). Because prostate carcinoma (PCa) lacks basal cells, the absence of basal cell as determined by 34betaE12 can aid in the confirmation of a histologically suspicious lesion. However, false-negative staining occurs because of patchy cytoplasmic staining, making a definitive diagnosis difficult. A recently identified basal cell marker p63, a p53 homologue, stains basal cell nuclei but not secretory cells. The aim of this study is to determine if the p63 antibody offers any clinically useful advantage over 34betaE12 in the diagnosis of challenging atypical prostate lesions. Ninety-four cases, comprised of 25 consecutive prostate NBX and 2 TURP with an atypical suspicious focus, 55 NBX cases of histologically unequivocal PCa and 12 TURP specimen removed for benign prostate hyperplasia, were stained with the monoclonal antibodies 34betaE12 and 4A4 anti-p63. Basal cell staining intensity, percentage basal cell-positive glands in benign, malignant, and atypical foci, and number of benign glands not staining were evaluated for 34betaE12 and p63 stains. A total of 67 prostate NBX cases, including one TURP, were diagnosed with PCa, 1 atypical small acinar proliferation, 10 benign, and 4 cases excluded because of lost tissue on step sections. None of the 67 PCa NBX cases demonstrated 34betaE12 or p63 immunoreactivity (100% specific). Whereas 57 of 108 (53%) prostate NBX cores from 78 cases demonstrated a similar percentage of basal cell staining for both antibodies, 45 of 108 (41%) NBX cores demonstrated a higher percentage of p63 basal cell staining in benign glands. Only 6 of 108 NBX (6%) cores had a higher percentage of basal cell staining with 34betaE12 (Wilcoxon signed rank test, p <0.0001). Lack of basal cell staining in more than two benign glands occurred in 25 of 108 (23%) and 10 of 108 (9%) prostate NBX cores stained with 34betaE12 and p63, respectively. In the vast majority of atypical cases, both 34betaE12 and p63 staining differences were not clinically significant, except in 2 of 27 (7%) cases p63 offered diagnostic utility beyond the 34betaE12 immunostain. p63 in these cases demonstrated discontinuous but strong staining in atypical glands and adjacent benign glands, whereas 34betaE12 failed to stain optimally in this critical area. For 12 TURP cases the mean percentage basal cell positivity in benign glands was 75% and 95% for 34betaE12 and p63, respectively (p = 0.006). Lack of basal cell staining in more than two glands occurred in 12 of 12 (100%) and 2 of 12 (17%) TURP specimens stained with 34betaE12 and p63, respectively (p <0.0001). In summary, 34betaE12 and p63 are highly specific for basal cells and therefore are negative in areas of PCa. p63 is more sensitive than 34betaE12 in staining benign basal cells, particularly for TURP specimens, offering slight advantage over 34betaE12 in diagnostically challenging cases. p63 may be used as an alternative to 34betaE12 stain for difficult prostate lesions.
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PMID:Comparison of the basal cell-specific markers, 34betaE12 and p63, in the diagnosis of prostate cancer. 1221 72

A rare case of olfactory neuroepithelioma with rhabdomyoblasts in a 61-year-old man was investigated using electron microscopic and immunohistochemical methods. A large tumor enhanced by gadolinium-diethylenetriamine pentaacetic acid (DTPA) was demonstrated on magnetic resonance imaging (MRI), located within the anterior cranial fossa without bone destruction. The tumor mostly consisted of small cells with scant cytoplasm. Tubular rosettes were often found. Immunoreactivity for cytokeratin and epithelial membrane antigen (EMA) was strongly positive. Most of the tumor cells were shown to be positive for neuron-specific enolase (NSE) and vimentin and weakly positive for synaptophysin and S-100. Rhabdomyoblasts, which showed oval cells with abundant eosinophilic cytoplasm and a nucleus sometimes displaced toward the periphery of the cell body, were frequently intermingled with the tumor cells. The immunoreactivity for myoglobin was frequently positive in these oval cells. The MIB-1 index showed high values, of 20%-40%. About 10% of the tumor cells revealed positivity for p53 protein and vascular endothelial growth factor (VEGF). Ultra-structurally, numerous junctional complexes were observed between cell bodies and processes. The cell processes frequently contained numerous microtubules. There were sometimes numerous filaments with small aggregates of Z-band material and thick filament-ribosomal complexes in the oval cells. They were concluded to be consistent with rhabdomyoblasts on light microscopic and immunohistochemical findings.
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PMID:An ultrastructural and immunohistochemical study of olfactory neuroepithelioma with rhabdomyoblasts. 1235 37

The eustachian tube epithelial cells play an important role in the initial pathogenesis of otitis media. In order to study the role of the eustachian tube epithelial cells in the pathogenesis of otitis media, we have established a rat eustachian tube epithelial cell line. The cell line was derived by infecting primary cultures of eustachian tube epithelial cells with the adenovirus 12-simian virus 40 (Adl2-SV40) hybrid virus. The immortalized cells have retained the morphological characteristics of the parental cells and show positive staining with anti-cytokeratin antibodies (a marker for epithelial cells), but not with anti-vimentin antibodies (a fibroblast marker). The cells have been in continuous culture for more than 10 months and have undergone 38 passages. Western blotting and cell staining have confirmed the expression of the SV40 T antigen and p53. Chromosomal analysis indicates that the cell line is aneuploid and derived from male rat epithelial cells. Together, our results suggest that the cell line originated from eustachian tube epithelial cells from a male rat and was successfully immortalized by the Ad12-SV40 virus.
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PMID:Immortalization of rat eustachian tube epithelial cells by adenovirus 12-simian virus 40 hybrid virus. 1238 62

Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from malignant melanocytic neoplasms or predicting survival time.
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PMID:A comparative review of melanocytic neoplasms. 1245 Jan 97

Twenty-three patients with primary small cell carcinoma of the uterine cervix are presented. Their ages ranged between 23 and 63 years (average, 43 years). Blood spotting or vaginal bleeding was the most common clinical presentation. Histologically, the tumors were densely cellular and showed trabecular nesting or a sheet-like pattern. The neoplastic cells had scant cytoplasm, round nuclei, absence of nucleoli, and finely dispersed chromatin. Nuclear molding, single cell necrosis, and high mitotic activity were found in all tumors. There was a minor component of large cell neuroendocrine carcinoma in three cases, while foci of adenocarcinoma were identified in two cases. Immunohistochemical studies were performed in all 23 tumors which showed immunoreactivity for cytokeratin. Ten small cell carcinomas were immunoreactive for chromogranin, 13 for synaptophysin, and 10 expressed p53 protein. Treatment modalities included hysterectomy alone or combined with chemotherapy and/or radiation therapy. A few patients received chemotherapy and/or radiation alone. Follow-up information was obtained in 22 cases; 15 patients died of tumor between 6 and 43 months, while seven patients have remained alive 12 to 273 months. One patient was lost to follow-up. Small cell carcinoma of the cervix is a highly aggressive neoplasm. However, early diagnosis and combined therapeutic modalities may lead to longer survival in some patients. Although the use of immunohistochemistry may be helpful in the diagnosis, small cell carcinoma still remains a morphologic diagnosis.
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PMID:Small cell carcinoma of the cervix: a clinicopathologic and immunohistochemical study of 23 cases. 1247 83

Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also up-regulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computer-assisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).
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PMID:Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications. 1248 Oct 10

Diagnostically reliable identification of prostatic basal cells has depended on staining for high molecular weight cytokeratin. The diagnosis of malignancy is often based on the absence of basal cells. False-negative staining is occasionally observed. Thus, a second method of identifying basal cells might prove useful. Selective expression of p63, a homologue of p53, has been demonstrated in prostatic basal cells. We investigated the diagnostic utility of p63 staining in 70 consecutive specimens for which the differential diagnosis included prostatic adenocarcinoma: 68 needle biopsies and 2 transurethral resection blocks. High molecular weight cytokeratin staining was the gold standard when material was available. A total of 61 specimens were diagnosed as carcinoma, 4 as atrophy, 2 as high-grade prostatic intraepithelial neoplasia, 2 as unclassified collections of benign glands, and 1 as carcinoma versus high-grade prostatic intraepithelial neoplasia. Sections mounted on charged slides were used for p63 staining for 14 specimens. Sections previously hematoxylin and eosin stained on uncharged slides were used for 56 specimens. In every case in which there was successful p63 staining (55 specimens), basal cells in benign lesions were properly marked and other cell types were not stained. Uninformative staining in the remaining 15 specimens was due to failure of tissue adherence in 14 specimens in which sections were on uncharged slides and, in 1 specimen, to poor positive internal control staining of benign glands. Thus, p63 staining was informative in 55 of 56 specimens (98%) for which there was material for examination. No case with satisfactory p63 and high molecular weight staining showed disagreement between the two stains. An additional group of 21 transurethral resection specimens was stained (p63 and high molecular weight cytokeratin). There was less false-negative staining for p63 compared with the case of high molecular weight cytokeratin. No false-positive staining was seen. We conclude that p63 staining is at least as sensitive and specific for the identification of basal cells in diagnostic prostate specimens as is high molecular weight cytokeratin staining.
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PMID:Diagnostic utility of immunohistochemical staining for p63, a sensitive marker of prostatic basal cells. 1248 Oct 11


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