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)

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors. The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, alpha-smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis. Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and alpha-SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and alpha-SMA all showed a distinctive pattern of staining in MACs. Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.
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PMID:Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis. 1125 20

Microcystic adnexal carcinoma (MAC) is a slow growing, locally aggressive sweat gland tumor. It predominantly affects the face and tends to recur despite local excision. Microscopically, MAC is characterized by a stratified proliferation of microcysts, cords, and ducts of cells that show squamous or adnexal differentiation. Atypia and mitoses are almost completely absent and metastatic deposits are rare and mostly limited to the regional lymph nodes; rather than real metastases, they might be the result of local extension of the tumor through perineurial spaces. We report a case of adnexal carcinoma with architectural features of MAC that displayed also marked nuclear pleomorphism and hyperchromasia with squamous pearl formation and a widespread strong p53 immunoreaction. The lesion behaved as a high-grade neoplasm with rapid growth, carcinosarcomatous metaplastic transformation in a relapse, and what were clinically suspected to be metastases. The literature contains several other examples reported as metastatic high-grade MAC, one of them with widespread distant metastases. We therefore want to sound an alert about the possible existence of tumors displaying microscopic findings characteristic of the aggressive forms of sweat gland carcinoma (nuclear pleomorphism and hyperchromasia, vascular invasion, and necrosis) in addition to architectural features of MAC. Whether these tumors should be called high-grade MACs or belong to a separate category remains an open issue until more cases are reported and bridge cases are eventually documented.
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PMID:High (nuclear) grade adnexal carcinoma with microcystic adnexal carcinoma-like structural features. 1687 Oct 41

Microcystic adnexal carcinoma (MAC) is a rare cutaneous malignancy. Due to its rarity, the molecular characteristics and treatment for metastatic MAC remain undefined. Here we present, as far as we are aware, the first case of metastatic MAC with DNA sequencing results indicating a mutation in TP53 and chromosomal losses in cyclin dependent kinase inhibitor 2A (CDKN2A) and cyclin dependent kinase inhibitor 2B (CDKN2B). In addition, this is the first case of metastatic MAC with a documented objective response to systemic antineoplastic chemotherapy (carboplatin and paclitaxel) confirmed by positron emission tomography/computed tomography. Our case increases the very limited medical knowledge of this rare disease.
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PMID:Metastatic Microcystic Adnexal Carcinoma with DNA Sequencing Results and Response to Systemic Antineoplastic Chemotherapy. 2887 Sep 41

Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its infiltrative growth and histopathologic overlap with benign adnexal tumors, often posing challenges to both diagnosis and management. Understanding the molecular underpinnings of microcystic adnexal carcinoma may allow for more accurate diagnosis and identify potential targetable oncogenic drivers. We characterized 18 microcystic adnexal carcinomas by targeted, multiplexed PCR-based DNA next-generation sequencing of the coding sequence of over 400 cancer-relevant genes. The majority of cases had relatively few (<8) prioritized somatic mutations, and lacked an ultraviolet (UV) signature. The most recurrent mutation was TP53 inactivation in four (22%) tumors. Frame-preserving insertions affecting the kinase domain of JAK1 were detected in three (17%) cases, and were nonoverlapping with TP53 mutations. Seven (39%) cases demonstrated copy number gain of at least one oncogene. By immunohistochemistry, p53 expression was significantly higher in microcystic adnexal carcinomas with TP53 mutations compared with those without such mutations and syringomas. Similarly, phospho-STAT3 expression was significantly higher in microcystic adnexal carcinomas harboring JAK1 kinase insertions compared with those with wild-type JAK1 and syringomas. In conclusion, microcystic adnexal carcinomas are molecularly heterogeneous tumors, with inactivated p53 or activated JAK/STAT signaling in a subset. Unlike most other nonmelanoma skin cancers involving sun-exposed areas, most microcystic adnexal carcinomas lack evidence of UV damage, and hence likely originate from a relatively photo-protected progenitor population in the dermis. These findings have implications for the biology, diagnosis, and treatment of microcystic adnexal carcinomas, including potential for therapeutic targeting of p53 or the JAK/STAT pathway in advanced tumors.
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PMID:Next-generation sequencing implicates oncogenic roles for p53 and JAK/STAT signaling in microcystic adnexal carcinomas. 3185 79

Microcystic adnexal carcinoma (MAC) is a rare, locally aggressive malignant neoplasm that derives from cutaneous eccrine/apocrine glands. MAC is classified as an eccrine/apocrine gland tumor and usually occurs in the skin. Here, we characterized and compared two cases of MAC. One is extremely rare in terms of its occurrence in the tongue. The other occurred in the lip, which is common. Histories of disease, diagnosis, and differentials were reviewed by the attending physicians. Hematoxylin and Eosin (HE) slides were evaluated by an experienced pathologist. Immunological markers for malignant eccrine/apocrine gland tumors were used to characterize the tumor's nature. The examined markers included EMA, CK5/6, CK8/18, CK7, CK20, p63, S-100, Calponin, CD10, MYB, Bcl-2, Her-2, CD34, SMA, p53, CD43, CD117, and Ki-67. Both patients were males, presented with painless lumps in the lower lip and in the tongue, respectively. Both lumps were similar in terms of appearance, being whitish, and infiltrative with irregular borders. Both tumors also had similar histological features with nests of bland keratinocytes, cords, and ductal differentiation filled with Periodic acid-Schiff (PAS)-positive eosinophilic material. In both cases, circular or ovary tumor cells invaded into muscles and nerves. All tumor cells were CK5/6, CK8/18, EMA, and CK7 positive. Particularly, keratinocytes were p63 positive, and paraductal cells were p63, S-100, and SMA positive. Therefore, the rare case of MAC in the tongue appears to derive from the salivary gland.
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PMID:Microcystic adnexal carcinoma: report of rare cases. 3191 68