Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined. A case of epithelial-myoepithelial tumor of the lung arising from bronchial mucosa-submucosa and occurring as a polypoid lesion of the upper left bronchus in a 47-year-old man is reported. The tumor did not infiltrate the cartilaginous wall of the bronchus and showed a biphasic histological appearance with a double layering of epithelial and myoepithelial cells. Myoepithelial spindle cells with eosinophilic cytoplasm were also observed. Mitotic figures were very rare and necrosis absent. Immunohistochemical study for epithelial and muscular markers confirmed the presence of a double-cell component in the tumor, namely epithelial and myoepithelial. The patient is alive and well, with no evidence of recurrent or metastatic disease 6 months after surgery. On the basis of the present case and the six previously reported cases, we suggest using the noncommittal term pulmonary epithelial-myoepithelial tumor of unproven malignant potential (PEMTUMP) for this type of neoplasm. In addition, we first introduce p63 as a novel marker for highlighting the myoepithelial cells of the respiratory tract and speculate on the role of these cells in the development of this unusual tumor.
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PMID:Pulmonary epithelial-myoepithelial tumor of unproven malignant potential: report of a case and review of the literature. 1135 64

Myoepithelial cells (MCs) constitute the basal cell layer of normal mammary epithelia, and their identification is of particular diagnostic value because they are retained in most benign lesions while being lost in malignancy. Several MC immunocytochemical markers are currently available for diagnostic purposes, with special reference to smooth muscle-related antigens. p63 is a member of the p53 gene family, and its germline mutations are associated with severe mammary developmental defects in both rodents and humans. Different p63 isoforms have been identified, some of which (DeltaNp63) are preferentially expressed in the epithelial basal cells of different organs and have been considered as possible markers of stem cells/reserve cells. We investigated immunohistochemically 384 samples of normal and diseased human breast, including 300 invasive carcinomas, using four antibodies recognizing all p63 isoforms, or the DeltaNp63 isoforms. Twenty cytologic specimens were also investigated. Furthermore, snap-frozen tissue samples from three fibroadenomas and 10 invasive ductal carcinomas with their paired non-neoplastic tissues and three corresponding lymph node metastases were evaluated for the expression of p63 mRNA by RT-PCR. In normal breast tissue p63 immunoreactivity was confined to the nuclei of MCs. In all benign lesions p63-immunoreactive cells formed a continuous basal rim along the epithelial structures. Stromal cells, and in particular myofibroblasts, were consistently unreactive. Adenomyoepitheliomas showed nuclear staining in most neoplastic cells. A peripheral rim of p63-immunoreactive cells was retained surrounding lobular and ductal carcinoma in situ, although it was discontinuous as opposed to the normal structures. Invasive breast carcinomas were consistently devoid of nuclear p63 staining, with the exception of the two adenoid-cystic carcinomas, of the two ductal carcinomas with squamous metaplasia, and of 11 (4.6%) ductal carcinomas not otherwise specified, showing p63 immunoreactivity in a minor fraction (5-15%) of the neoplastic cells. In comparison with other MC markers, p63 was the most specific, being restricted exclusively to MCs, whereas antibodies to smooth muscle actin and, to a lesser extent, calponin also decorated stromal myofibroblasts. In the cytologic preparations p63 immunoreactivity was a consistent feature of "naked nuclei" and of a subset of cells surrounding benign epithelial clusters. RT-PCR experiments with primers specific for different p63 isoforms documented that normal tissues and fibroadenomas preferentially expressed the DeltaNp63 isoforms. Our study demonstrates that in normal and pathologic breast tissues MCs consistently express the DeltaNp63 isoforms. We suggest p63 as a reliable, highly specific, and sensitive MC marker in both histologic and cytologic preparations. Furthermore, because p63 immunoreactivity in adult epithelia is normally restricted to progenitor cells, it can be speculated that it might be a clue for the identification of the still elusive breast progenitor cells.
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PMID:p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. 1147 90

Identification of genes that are dysregulated in association with prostate carcinogenesis can provide disease markers and clues relevant to disease etiology. Of particular interest as candidate markers of disease are those genes that are frequently overexpressed. In this study, we describe a gene, alpha-methylacyl-CoA racemase (AMACR), whose expression is consistently up-regulated in prostate cancer. Analysis of mRNA levels of AMACR revealed an average up-regulation of approximately 9 fold in clinical prostate cancer specimens compared with normal. Western blot and immunohistochemical analysis confirms the up-regulation at the protein level and localizes the enzyme predominantly to the peroxisomal compartment of prostate cancer cells. A detailed immunohistochemical analysis of samples from 168 primary prostate cancer cases using both standard slides and tissue microarrays demonstrates that both prostate carcinomas and the presumed precursor lesion (high-grade prostatic intraepithelial neoplasia) consistently scored significantly higher than matched normal prostate epithelium; 88% of the carcinomas had a staining score higher than the highest score observed for any sample of normal prostate epithelium. Both untreated metastases (n = 32 patients) and hormone refractory prostate cancers (n = 14 patients) were generally strongly positive for AMACR. To extend the utility of this marker for prostate cancer diagnosis, we combined staining for cytoplasmic AMACR with staining for the nuclear protein, p63, a basal cell marker in the prostate that is absent in prostate cancer. In a simple assay that can be useful for the diagnosis of prostate cancer on both biopsy and surgical specimens, combined staining for p63 and AMACR resulted in a staining pattern that greatly facilitated the identification of malignant prostate cells. The enzyme encoded by the AMACR gene plays a critical role in peroxisomal beta oxidation of branched chain fatty acid molecules. These observations could have important epidemiological and preventive implications for prostate cancer, as the main sources of branched chain fatty acids are dairy products and beef, the consumption of which has been associated with an increased risk for prostate cancer in multiple studies. On the basis of its consistency and magnitude of cancer cell-specific expression, we propose AMACR as an important new marker of prostate cancer and that its use in combination with p63 staining will form the basis for an improved staining method for the identification of prostate carcinomas. Furthermore, the absence of AMACR staining in the vast majority of normal tissues coupled with its enzymatic activity makes AMACR the ideal candidate for development of molecular probes for the noninvasive identification of prostate cancer by imaging modalities.
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PMID:Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer. 1195 72

Immunohistochemical studies on metastatic carcinomas of unknown primary site are cost-effective and often allow a specific identification of the tumour origin, especially if the metastases are adenocarcinomas by light microscopy. Commercially available site-specific markers include prostate-specific antigen, thyroglobulin, thyroid transcription factor-1, uroplakin III, GCDFP-15, oestrogen and progesterone receptors, alpha-fetoprotein, the A103 monoclonal antibody against MART-1, cytokeratins 7 and 20, cytokeratins of basal cell type, p63, carcinoembryonic antigen, CA125, EMA, vimentin, HepPar-1, WT-1 and S100 protein. However, immunostaining with most of these markers does not show an absolute specificity for a certain primary site. For this reason, histopathologists interpretating staining results with these markers should take the available clinical data and the histological features of the metastatic carcinoma into consideration. These data are necessary to estimate the relative a priori probability of possible carcinomas. Based on Bayes' theorem, the a priori probability can then be used to calculate the diagnostically relevant predictive values for immunostaining results with the chosen markers.
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PMID:[Immunohistochemical diagnosis in cancer metastasis of unknown primary tumor]. 1208 86

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate has been considered to have indolent biologic potential. However, outcome data are scant, with only one documented metastasis and death. We describe clinicopathologic features of ACBCC in 19 patients and document outcome in 15. Patients ranged in age from 43 to 83 years. All but one presented with urinary obstruction. ACBCC was diagnosed by transurethral resection in 15 cases, by needle biopsy in 3 cases, and unexpected in 1 case. Four patients had concurrent acinar adenocarcinoma. Histologically, cribriform or adenoid cystic patterns predominated in 12 cases and basal cell carcinoma pattern in 7. Five cases had prominent perineural invasion. ACBCC was immunoreactive for p63 and cytokeratins 7 and 34 beta E12 but not cytokeratin 20. After diagnosis, 5 patients underwent radical prostatectomy, 2 underwent pelvic exenteration, and the rest had no treatment. ACBCC showed extraprostatic extension in 5 cases and involved the bladder margin in 3. Metastases developed in 4 (21%) patients: liver (2), lung (2), bowel (1), and corpus cavernosum (1). In 15 cases with follow-up (0.3-11.8 years), two patients died of cancer (at 1.5 and 3 years after diagnosis), 3 remain alive with cancer, and 10 have no evidence of cancer. Thus, ACBCC of the prostate is a potentially aggressive neoplasm requiring ablative therapy.
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PMID:Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. 1465 11

We studied the usefulness of a p63/P504S immunostain "cocktail" in evaluation of prostate biopsy specimens containing atypical acini suspicious for adenocarcinoma (AASA), high-grade prostatic intraepithelial neoplasia (HPIN), and small foci of adenocarcinoma and tested the sensitivity and specificity of the immunostain with tissue microarrays (TMAs) constructed from prostatectomy and lymphadenectomy specimens. We selected 40 cases containing a focus of adenocarcinoma (14 cases), AASA (7 cases), AASA with HPIN (7 cases), HPIN (6 cases), and atypical favor benign (6 cases). After p63/P504S immunostaining, 13 cases (33%) were reclassified: AASA with HPIN to HPIN only in 5 cases (13%), atypical favor benign to benign in 4 cases (10%), AASA to adenocarcinoma in 2 cases (5%), and atypical favor benign to AASA and atypical favor benign to HPIN in 1 case (3%) each. The diagnosis of adenocarcinoma was supported by immunostain in 14 cases. In TMA studies, the p63/P504S immunostain for adenocarcinoma and HPIN had sensitivity values of 97.2% and 86.2%, respectively, and specificity values of 99.7% and 81.6%, respectively. P504S stained 64 (74%) of 87 cores of metastatic cancers, and no p63-positive cells were identified in the metastases. The p63/P504S immunohistochemical stain is a sensitive, specific marker for prostatic adenocarcinoma and HPIN and useful in the evaluation of AASA in biopsy specimens.
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PMID:An analysis of the p63/alpha-methylacyl coenzyme A racemase immunohistochemical cocktail stain in prostate needle biopsy specimens and tissue microarrays. 1498 35

P63 is a recently discovered gene harbouring different isoforms by alternate splicing. The two main isoforms, TAp63 and Delta Np63, have opposite functions, being responsible for cell-cycle arrest and cell proliferation, respectively. In addition, new isoforms have been described with the same sequence as TAp63 and Delta Np63, but lacking exon 4 (Delta 4Tap63 and Delta Np73L). P63 as detected using immunohistochemistry is present in squamous cell carcinomas. To better define the role of p63 in squamous cell carcinomas of the oral cavity (OSCC), 39 patients were investigated using immunohistochemical analysis with a monoclonal antibody recognising all p63 isoforms and an anti-Ki67 antibody. Reverse-transcription polymerase chain reaction (PCR) and nested PCR were also performed using isoform-specific primers to evaluate the p63 mRNA expression pattern. Using immunohistochemistry, p63 was always present in OSCC, and its distribution was similar to that of Ki67. The percentage of positive cells increased from normal to neoplastic mucosa, but there was no relationship between the number of p63 positive cells and prognosis. P63 mRNA was found in all patients. The truncated isoforms Delta 4TAp63 and Delta Np73L were more frequently expressed in patients presenting with metastases. Delta Np73L was found in 66.6% of tumours with lymph-node metastases, but in only 33.3% of those devoid of lymph-node metastases at presentation. An impaired expression of the p63 isoforms might favour cell proliferation and indirectly enhance the metastasising capacity of OSCC.
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PMID:Pattern of p63 expression in squamous cell carcinoma of the oral cavity. 1499 91

The p53 tumor suppressor protein is a key mediator of an ATM-dependent DNA damage response cascade following cellular exposure to ionizing radiation. The p53-family members, p63 and p73, are highly similar to p53, yet are differentially activated by IR, UV and cis-platinum via ATM and c-abl/ATR signaling pathways. Loss of function of p53 can occur by mutation or degradation; giving rise to alterations in G(1) and G(2) cell cycle checkpoint control, cell death, DNA repair and genetic stability. The end result of these alterations can be the generation of radioresistant mutant tumor cells. Indeed, in isogenic systems, loss of p53 or p73 function has been associated with decreased chemosensitivity and radiosensitivity, in vitro. However, clinical data supporting a role for p53 genotype as an independent predictive factor for radiotherapy outcome continues to be controversial due to variable endpoints in clinical trial design and in methodology in detecting p53 function. Nonetheless, in carefully controlled radiotherapy studies where mutations in p53 have been detected using DNA sequencing or functional assays, the presence of mutant p53 can be associated with decreased local control following radiotherapy. This suggests that novel molecular treatment strategies specifically designed to re-institute normal p53 function within resistant tumors can be used as combined modality protocols to improve local control and maintain a therapeutic ratio. A future challenge lies in the pre-therapy determination of a 'molecular therapeutic ratio' for individual patients which could allow for specific prognostication based on p53 functional status and subsequent individualized therapy.
Cancer Metastasis Rev
PMID:The p53 protein family and radiation sensitivity: Yes or no? 1519 26

We evaluated 25 intraductal papillomas and 18 papillary carcinomas (invasive, 4; micropapillary ductal carcinoma in situ [DCIS], 5; cases originally classified as intracystic/intraductal papillary carcinoma, 9) by calponin, smooth muscle myosin heavy chain (SMM-HC), and p63 immunostains. Calponin, SMM-HC, and p63 labeled myoepithelial cells (MECs) in all intraductal papillomas and all micropapillary DCIS cases. The invasive papillary carcinoma cases were uniformly negative for all stains. The 9 cases originally diagnosed as intracystic/intraductal papillary carcinoma showed more variable results, with identification of an MEC layer in only 4 cases. Comparison of staining of MECs by these 3 stains showed that calponin was more sensitive and intense than SMM-HC; however, there was cross-reactivity with myofibroblastic cells. Staining with p63 was discontinuous, making interpretation of an intact myoepithelial layer difficult. Of 9 cases originally classified as intraductal papillary carcinoma, 5 showed absence of a basal MEC layer by immunohistochemical analysis. The lack of a basal MEC layer in these cases suggests a spectrum of progression from in situ to invasive disease and might help explain distant metastases from previously reported "intraductal papillary carcinoma."
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PMID:Myoepithelial cell staining patterns of papillary breast lesions: from intraductal papillomas to invasive papillary carcinomas. 1576 78

Breast ducts contain two types of epithelial cells, inner luminal cells and outer basal/myoepithelial cells. These cells can be distinguished by their immunophenotype. Cytokeratins (CKs) 8 and 18 are expressed in the luminal layer, whereas CK5/14 and the transcription factor p63 characterize the basal epithelial layer. We studied a population-based cohort of 288 sporadic ductal invasive cancers and found 9% positive for CK5/14 and 4% positive for p63. Using a highly sensitive polymer-based immunohistochemical staining, all sporadic tumors were positive for the luminal CK8/18, including those positive for CK5/14. Pairs of primary tumors and metastases (n = 38) were always concordant for CK5/14 expression. The majority of the CK5/14-positive cases were of histologic grade III (P = 0.0007) and steroid hormone receptor negative (P < 0.0001). CK5/14 expression was inversely associated with HER-2 oncogene amplification, but only in the subgroup of estrogen receptor-negative tumors (P = 0.007). In a separate set of 42 hereditary breast cancers, the majority (78%) of the BRCA1-associated tumors, but only one of 15 BRCA2-associated tumors was positive for CK5/14. In contrast to sporadic CK5/14-positive tumors, BRCA1-associated tumors displayed less intense CK8/18 staining, including some truly CK5/14-positive CK8/18-negative cases. These results suggest that CK5/14-positive sporadic breast cancers arise from glandularly committed progenitor cells rather than true CK8/18-negative basal cells.
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PMID:Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors. 1599 Aug 99


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