Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is among the most common malignancies. It is estimated that 1 in 6 men in the United States will be diagnosed with this disease. Despite the high prevalence and importance of prostate cancer, the molecular mechanisms underlying its development and progression remain poorly understood. This article reviews new information about the roles of oxidants and electrophiles in prostate cancer; the potential importance of chronic inflammation and atrophy in prostate carcinogenesis, and implications for chemoprevention; evidence supporting telomere shortening and genetic instability in the etiology of prostate cancer; and alpha-methylacyl-coenzyme A racemase (AMACR) as a potential marker for prostate carcinogenesis. These new results show that at least some high-grade prostatic intraepithelial neoplasias (PIN) and early adenocarcinomas appear to arise from proliferative inflammatory atrophy (PIA). Inflammation and other environmental factors may lead to the destruction of prostate epithelial cells, and increased proliferation may occur as a response to this cell death. Such proliferation may be mechanistically related to decreased p27(Kip1) observed in PIA. The decreased apoptosis associated with these events may also be related to increased expression of Bcl-2. Increased oxidant and electrophile stress in the setting of increased proliferation associated with these events may lead to elevated glutathione S-transferase P1 (GSTP1) expression as a genomic-protective measure. However, aberrant methylation of the CpG island of the GSTP1 gene promoter silences GSTP1 gene expression and protein levels, setting the stage for additional genetic damage and accelerated progression toward PIN and carcinoma. Additional results show that AMACR may be an important new marker of prostate cancer, and its use in combination with p63 staining may provide the basis for an improved method for identification of prostate cancer.
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PMID:Human prostate cancer precursors and pathobiology. 1460 18

Thymic carcinoma and thymoma are primary neoplasms of the anterior mediastinum that can involve the lung and pleura in advanced stages or, in rare instances, occur as primary pleural tumors. Thus these tumors may be encountered in thoracic and pleural biopsy specimens. Recognizing the immunohistochemical patterns of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma may be helpful in avoiding confusion with malignant mesothelioma and pulmonary carcinoma, both of which are major differential diagnoses in this location. Accordingly, in the present study we examined the expression of calretinin, mesothelin, cytokeratin (CK) 5/6, thrombomodulin, HBME-1, Wilms' tumor-1 (WT-1), Ber-EP4, MOC-31, BG-8, B72.3, carcinoembryonic antigen (CEA), CD15, thyroid transcription factor-1 (TTF-1), p63, and CD5 in 22 thymic carcinomas and 35 thymomas, and compared the results with those of malignant mesothelioma and pulmonary adenocarcinoma. Around 1/3 of thymic carcinomas were positive for calretinin and/or mesothelin. Both thymic carcinomas and thymomas were frequently positive for CK 5/6. Immunoreactivity for HBME-1 was seen in 4 thymic carcinomas and 10 thymomas. Except for 1 thymic carcinoma being positive for WT-1, all other thymic carcinomas and thymomas were negative for WT-1 and thrombomodulin. None of the thymic carcinomas and thymomas expressed TTF-1. More than 70% of the thymic carcinomas were positive for Ber-EP4, BG-8, and CD15. The positive rates of MOC-31, B72.3, and CEA in thymic carcinomas were in the middle between those in mesothelioma and pulmonary adenocarcinoma. All thymic epithelial tumors revealed nuclear immunoreactivity for p63. Nine thymic carcinomas (41%) expressed CD5. We found that a panel of positive p63, negative thrombomodulin, WT-1, and TTF-1 is most discriminatory for thymic epithelial tumors. Other mesothelial (calretinin and mesothelin) and epithelial (Ber-EP4, BG-8, and CD15) markers are less contributory in discerning thymic epithelial tumors due to their overlapping expression with malignant mesothelioma and pulmonary adenocarcinoma. Given the complexity of the staining patterns among the different entities, proper immunohistochemical stainings should be selected and interpreted with caution, and correlated with clinicopathologic findings in the differential diagnoses of thoracic biopsy specimens.
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PMID:Expression of calretinin and other mesothelioma-related markers in thymic carcinoma and thymoma. 1465 17

Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N=12), grade I invasive ductal carcinoma (N=15), grade II invasive ductal carcinoma (N=15), grade III invasive ductal carcinoma (N=15), tubular carcinoma (N=8), lobular carcinoma (N=10), and medullary carcinoma (N=10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P<0.001), but not between EBNA-1 and p53 (P=0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.
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PMID:Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein-Barr virus-related breast malignancies? 1468 49

Collagenous spherulosis (CS) is an incidental finding that usually occurs in association with benign proliferative and preinvasive lesions. Adenomyoepithelioma is a biphasic neoplasm of the breast, composed of both luminal epithelial and myoepithelial cells. Despite the common epimyoepithelial histogenesis, CS has never been described in association with adenomyoepithelioma. This report describes the case of a 48 year old woman who presented with CS of the breast in an adenomyoepithelioma. The combination of these two benign lesions led to diagnostic difficulties; namely, differentiation from adenoid cystic carcinoma, but also cribriform carcinoma and cylindroma of the breast. Antibodies to the oestrogen receptor, progesterone receptor, p63, and c-kit (CD117) proved to be useful adjuncts to differentiate between these lesions.
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PMID:Collagenous spherulosis in an adenomyoepithelioma of the breast. 1469 44

Analogous to mixed tumors of salivary glands (" pleomorphic adenomas" ), cutaneous mixed tumors (" chondroid syringomas" ) contain a ductal (epithelial) component and a variably prominent myoepithelial component. Tumors showing purely myoepithelial differentiation (myoepitheliomas) have only recently been recognized to arise in the dermis, and to date very few cases have been described. To characterize these tumors further, 14 cutaneous myoepithelial tumors were retrieved from the authors' consult files. Eleven patients were male and 3 were female; their median age was 22.5 years (range, 10 to 63 years), and 7 patients were between 10 and 20 years old. Tumor size ranged from 0.5 to 2.5 cm (mean, 1.1 cm). Most tumors arose on the extremities: 6 on the upper limbs, 6 on the lower limbs, and 1 each on the back and nose. Ten tumors were limited to the dermis, and 5 also extended into superficial subcutis. Thirteen tumors were myoepitheliomas (lacking ductal differentiation), and 1 tumor was a myoepithelial carcinoma (exhibiting severe cytological atypia and a high mitotic rate). Histologically, 7 tumors were solid, composed of ovoid to spindled, histiocytoid, or epithelioid cells with no significant stroma, and 7 were predominantly lobulated, with cords or nests of epithelioid, plasmacytoid, or spindled cells with a variably reticular architecture and a chondromyxoid or collagenous/hyalinized stroma. One tumor was composed solely of plasmacytoid (hyaline) cells, and 1 exhibited extensive adipocytic differentiation. Among the 13 myoepitheliomas, mitoses ranged from 0 to 6 per 10 high-power fields (HPFs) (mean, 1.5); 8 tumors contained no mitoses. The myoepithelial carcinoma had 39 mitoses per 10 HPFs. By immunohistochemistry, all cases were reactive for epithelial markers (keratins and/or epithelial membrane antigen [EMA]); 13 of 14 (93%) expressed S-100 protein, 10 of 11 expressed (91%) calponin, 11 of 14 (79%) expressed EMA, 9 of 14 (64%) expressed keratins, 8 of 14 (57%) expressed smooth muscle actin, 7 of 14 (50%) expressed glial fibrillary acidic protein, 3 of 11 (27%) expressed p63, and 1 of 6 (17%) expressed desmin. All 5 cases without keratin staining were diffusely positive for EMA, and all of these cases showed a solid growth pattern. Follow-up was available for 8 patients (median follow-up, 40 months; range, 6 months to 9 years); 3 tumors (38%) recurred locally, and 1 tumor (13%) also metastasized to the lymph nodes. The case that resulted in recurrence and metastasis had the highest mitotic rate (6 per 10 HPFs) of the cytologically benign tumors. Follow-up information was not available for the myoepithelial carcinoma. This study suggests that approximately 50% of cutaneous myoepitheliomas are distinctive lesions composed of a solid proliferation of cells with abundant eosinophilic syncytial cytoplasm, which often lack immunostaining for keratin, whereas the remainder demonstrate focally reticular architecture and myxoid stroma or plasmacytoid cells, similar to their counterparts in salivary gland and soft tissue. Whereas most cutaneous myoepitheliomas behave in a benign fashion, there is apparently a significant risk for local recurrence but a low metastatic potential.
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PMID:Cutaneous myoepithelioma: a clinicopathologic and immunohistochemical study of 14 cases. 1474 20

The pure in situ form of salivary duct carcinoma, also known as intraductal carcinoma, is very rare, and its existence is controversial. We describe a case arising from the minor salivary glands. The patient was a 44-year-old woman who presented with a painless mass in the buccal mucosa. On microscopic examination, the tumor comprised crowded and smooth-contoured epithelial units exhibiting a fenestrated or cribriform pattern, occasionally punctuated by comedonecrosis. An attenuated layer of myoepithelial cells could be demonstrated around all the islands by immunostaining for p63 and actin, indicating absence of an invasive component. The patient remained well following local excision. This case, together with other reported cases, suggests that intraductal carcinoma is a distinct entity. It may represent the preinvasive phase of some invasive salivary duct carcinomas but by itself is nonmetastasizing and associated with an excellent prognosis.
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PMID:Intraductal carcinoma of the oral cavity: a case report and a reappraisal of the concept of pure ductal carcinoma in situ in salivary duct carcinoma. 1564 87

Most models suggest that the cell of origin of papillary carcinoma is the mature thyroid follicular epithelial cell. In a recent study, p63 was detected in papillary carcinoma, Hashimoto's thyroiditis, and in squamoid aggregates and solid cell nests (SCNs), embryonic remnants found sporadically in the fully developed thyroid. In the present study, the relationship between solid cell nests and papillary carcinoma was investigated further. Four-micrometer sections from 88 routinely fixed and processed archival thyroidectomy specimens were pretreated with citric acid pH 6.0 for antigen retrieval, then incubated overnight with anti-p63 monoclonal antibody 4A4. Slides were stained with a streptavidin-biotin kit and diaminobenzidine as chromogen and were counterstained with hematoxylin. Squamoid aggregates or SCNs were noted in 21 specimens. Several morphologic variants of SCNs were found, all of which displayed p63 positivity. These included undifferentiated SCNs and those displaying commitment toward squamoid and ciliated glandular differentiation. Small, morphologically inconspicuous aggregates of p63-positive cells were commonly found in Hashimoto's thyroiditis. Commitment of p63-positive undifferentiated cells toward thyroid follicular epithelial differentiation was occasionally noted. One SCN variant, also associated with Hashimoto's thyroiditis, was a floretlike arrangement of p63-positive cells with fusiform nuclei. p63 staining was strong and uniform in some SCNs, but in other SCNs it was compartmentalized and homologous to stem cell-staining patterns in normal squamous or bronchial epithelia. Stem cell-like staining, associated with compartmentalized p63 staining or p63-positive undifferentiated cells, was noted in 7 of 27 papillary carcinomas. p63 immunostaining is a highly sensitive means of detecting SCNs. p63 expression patterns in SCNs and a subset of papillary carcinomas are closely homologous to stem cell-associated p63 staining patterns that have been described elsewhere in squamous and bronchial epithelia. We propose a stem-cell-associated model of papillary carcinoma oncogenesis that suggests that (1) p63-positive embryonal remnants rather than mature follicular cells are the cells of origin of a subset of papillary carcinomas; (2) these p63-positive cells are pluripotent and may stay undifferentiated or undergo benign squamoid or glandular maturation, may undergo thyroid follicular epithelial differentiation, may undergo oncogenic change leading to papillary carcinoma, or may trigger an immune reaction, resulting in lymphoid infiltration and Hashimoto's thyroiditis; and (3) Hashimoto's thyroiditis and papillary carcinoma may therefore be linked etiologically, because both disorders may be initiated by the same population of pluripotent p63-positive embryonal stem cell remnants.
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PMID:Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and hashimoto's thyroiditis: A stem cell hypothesis of papillary carcinoma oncogenesis. 1594 29

Abnormalities in the p53 gene are regarded as the most consistent of the genetic abnormalities associated with oral squamous-cell carcinoma. Two related members of the p53 gene family, p73 and p63, have shown remarkable structural similarity to p53, suggesting possible functional and biological interactions. The purpose of this study was to investigate the differential expression of p73, p63 and p53 genes for DMBA-induced hamster buccal-pouch squamous-cell carcinoma. Immunohistochemical analysis for protein expression and reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNA expression were performed for 40 samples of hamster buccal pouches, the total being separated into one experimental group (15-week DMBA-treated; 20 animals) and two control groups (untreated and mineral oil-treated; 10 animals each). Using immunohistochemical techniques, nuclear staining of p53 and p73 proteins was detected in a subset of hamster buccal-pouch tissue specimens treated with DMBA for a period of 15 weeks, whereas p63 proteins were noted for all of the 20 hamster buccal-pouch tissue specimens treated with DMBA for 15 weeks as well as for all of the untreated and mineral oil-treated hamster buccal-pouch tissue specimens. Differential expression of p63, p73 and p53 protein for the experimental group was as follows: p63+/p73+/p53+ (n = 14; 70%); p63+/p73+/p53- (n = 2; 10%); p63+/p73-/p53- (n = 4; 20%) and p63+/p73-/p53- (untreated [n = 10] and mineral oil-treated mucosa [n = 10]; 100% each). Upon RT-PCR, DeltaNp63mRNA was detected within all of the 20 hamster buccal-pouch tissue specimens treated with DMBA for 15 weeks, whereas expression of TAp63 was not detected. Furthermore, p73 mRNA was identified for 16 of the hamster buccal-pouch tissue specimens treated with DMBA for 15 weeks, whereas p53 mRNA was noted for 14 15-week DMBA-treated pouches. The proportional (percentage) expression of DeltaNp63, p73 and p53 mRNA for the hamster buccal-pouch tissue specimens treated with DMBA for 15 weeks was noted to be consistent with the findings using immunohistochemical techniques. A significant correlation between p53, p63 and p73 expression (protein and mRNA) was demonstrated for the hamster buccal-pouch carcinoma samples. Our results indicate that both p73 and p63 may be involved in the development of chemically induced hamster buccal-pouch carcinomas, perhaps in concert with p53.
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PMID:Differential expression of p53, p63 and p73 protein and mRNA for DMBA-induced hamster buccal-pouch squamous-cell carcinomas. 1515 15

Diagnosis of prostate needle biopsies can be challenging, particularly when the atypical areas of interest are very small. The utility of immunostains for high-molecular-weight cytokeratin (34betaE12) to highlight prostatic basal cells in these cases is well established, and recent reports also document the utility of immunostains for p63 (a marker that stains the nuclei of prostate basal cells) for this purpose. Several investigators have demonstrated that immunostaining for P504S, a cytoplasmic protein that is overexpressed in a high percentage of prostate cancers and in many cases of high-grade prostatic intraepithelial neoplasia (PIN), can also be of use in the diagnosis of prostate biopsies. Because of the cytoplasmic localization of P504S and nuclear localization of p63, the authors hypothesized that a cocktail of these two antibodies might allow simultaneous demonstration of P504S and p63 using a single immunostain. In this report the authors describe the successful use of a cocktail of p63/P504S for immunohistochemical staining of prostate tissue. Two different staining approaches were investigated, with essentially identical results. This cocktail localizes P504S in the cytoplasm of prostate carcinoma cells and high-grade PIN and demonstrates the nuclei of prostatic basal cells, providing information on both the status of P504S and the presence or absence of basal cells with a single immunostain. This cocktail can be of great utility in the examination of diagnostically challenging prostate specimens.
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PMID:Use of p63/P504S monoclonal antibody cocktail in immunohistochemical staining of prostate tissue. 1516 24

Abnormalities in the p53 gene have been regarded as the most consistent genetic abnormalities detected in head and neck squamous cell carcinogenesis. Two new members of the p53 gene family, p73 and p63, have recently been identified. We investigated the expression of the two N-terminal p63 isoforms (TA and deltaN isoforms) in human primary well-differentiated buccal squamous cell carcinoma. Both TAp63 and deltaNp63 isoforms were detected in the basal/suprabasal layers of all of the five specimens of normal buccal mucosa. The deltaNp63 isoform was found in all of the 23 specimens of human primary well-differentiated buccal carcinoma whereas TAp63 isoform was absent in 18 (78.3%) of the 23 specimens. The immunostaining patterns of both TAp63 and deltaNp63 isoforms were similar in that the p63 positivity was noted mainly in the peripheral cells of tumor nests whereas negative staining was observed in the areas with keratin pearl formation. A higher number of T3-T4 patients and patients with recurrence showed negative staining of TAp63 than T1-T2 patients and patients without recurrence but the difference was not statistically significant. These results suggested that specific p63 isoforms were associated with human oral squamous cell carcinogenesis. The deltaNp63 isoforms might be involved in epithelial differentiation and proliferation in human oral carcinogenesis whereas there was evidence for a possible role of TAp63 under-expression in human oral tumorigenesis.
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PMID:Expression of p63 (TA and deltaN isoforms) in human primary well differentiated buccal carcinomas. 1518 14


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