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)

Most large bowel cancers are moderately to well-differentiated adenocarcinomas comprised chiefly or entirely of glands lined by tall columnar cells. We have identified a subset of poorly differentiated colon carcinomas with a distinctive histopathological appearance that we term large cell minimally differentiated carcinomas (LCMDCs). These tumors likely include a group of poorly differentiated carcinomas previously described by others as medullary adenocarcinomas. To better understand the pathogenesis of these uncommon neoplasms, we compared molecular features of 15 LCMDCs to those present in 25 differentiated adenocarcinomas (DACs) of the colon. Tumors were examined for alterations commonly seen in typical colorectal carcinomas, including increased p53 and beta-catenin immunoreactivity, K-ras gene mutations, microsatellite instability, and loss of heterozygosity of markers on chromosomes 5q, 17p, and 18q. In addition, tumors were evaluated by immunohistochemistry for CDX2, a homeobox protein whose expression in normal adult tissues is restricted to intestinal and colonic epithelium. Markedly reduced or absent CDX2 expression was noted in 13 of 15 (87%) LCMDCs, whereas only 1 of the 25 (4%) DACs showed reduced CDX2 expression (P < 0.001). Nine of 15 (60%) LCMDCs had the high-frequency microsatellite instability phenotype, but only 2 of 25 (8%) DACs had the high-frequency microsatellite instability phenotype (P = 0.002). Our findings provide support for the hypothesis that the molecular pathogenesis of LCMDCs is distinct from that of most DACs. CDX2 alterations and DNA mismatch repair defects have particularly prominent roles in the development of LCMDCs.
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PMID:Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. 1173 73

Several histological variants of colorectal carcinoma have been reported, some of them bearing prognostic significance, others only incidental findings showing unusual morphological features. The current report was aimed to describe the histological, immunohistochemical and ultrastructural features of an oncocytic adenocarcinoma of the rectum occurring in a 66-year-old woman. Histologically, it was a moderately differentiated adenocarcinoma composed by glandular structures lined by eosinophilic cells. The latter showed abundant granular cytoplasm and large nuclei with prominent nucleoli. Several glandular structures contained intraluminal, basophilic and non-birifrangent microcalcifications. The tumour cells displayed consistent anti-mitochondrial antigen, carcinoembryonic antigen, p53, CDX2 and cytokeratin 20 immunoreactivity. Ultrastructurally, more than 80% of the cytoplasmic area was occupied by abnormal mitochondria, while exocrine or endocrine granules were undetectable. The tumour infiltrated the intestinal wall through the subserosal tissue, but lymph node or distant metastases were absent. The patient is disease free 22 months after surgery. Based on the above features, this case could be appropriately named oncocytic adenocarcinoma with intraluminal microcalcifications. Like gastric neoplasms showing similar morphologic features, this tumour might have a better prognosis, and the presence of microcalcifcations could help its proper recognition at a pre-operative stage.
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PMID:Oncocytic adenocarcinoma of the rectum with diffuse intra-luminal microcalcifications: the first reported case. 1295 3

The CDX2 homeobox transcription factor plays key roles in intestinal development and homeostasis. CDX2 is downregulated during colorectal carcinogenesis, whereas overexpression of CDX2 results in growth inhibition and differentiation of colon carcinoma and intestinal cells. However, the means by which CDX2 functions remain poorly understood. p21/WAF1/CIP1 is one of the cyclin-dependent kinase inhibitors. In addition to its role in cell cycle control, p21 plays critical roles in differentiation and tumor suppression. The overlapping in both the expression and function of CDX2 and p21 in the small intestine and colon strongly suggests a link between these two genes. By means of luciferase reporter and electrophoretic mobility shift assays, we show here that CDX2 transactivated and physically interacted with the promoter of p21 in a p53-independent manner. Moreover, overexpression of CDX2 increased the mRNA expression of p21 in HT-29 colon carcinoma cells, as demonstrated by reverse transcription-polymerase chain reaction. These data suggest that p21 is a transcriptional target of CDX2. Our results may thus provide a new mechanism underlying the functions of CDX2.
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PMID:CDX2, a homeobox transcription factor, upregulates transcription of the p21/WAF1/CIP1 gene. 1297 Jul 42

Appendiceal carcinoids range from well-differentiated endocrine tumor to well-differentiated endocrine carcinoma, while poorly differentiated (small cell) carcinoma has not been described in this site. We report herein a case of mixed intestinal-type adenocarcinoma associated with a small cell carcinoma arisen in a 35-year-old woman and clinically presenting as an appendiceal abscess. The resected tumor histologically appeared as a biphasic lesion composed of a nonmucinous adenocarcinoma closely juxtaposed with a poorly differentiated (small cell) endocrine carcinoma. The subsequent right hemicolectomy was unremarkable, but one pericolic lymph node showed a metastatic deposit consisting of the adenocarcinoma only. The patient thus underwent a chemotherapeutic protocol for colorectal cancer, and she is alive and well at the 65-month follow-up. Immunohistochemically, the adenocarcinoma strongly stained for cytokeratin 20 and carcinoembryonic antigen, while the endocrine component displayed a dot-like positivity for pan-cytokeratins and chromogranin. Of note, both components did not stain with CDX2 and p53. At genotypic analysis by microsatellite instability, both components shared many microsatellite alterations as well as a normal p53 gene setup, although small cell carcinoma harbored additional alterations. Clinical and molecular findings led us to consider this lesion as a clonal tumor in which the endocrine component seems to derive from a progressive differentiation of the adenocarcinoma following a glandular-to-endocrine sequence.
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PMID:Primary mixed adenocarcinoma and small cell carcinoma of the appendix: a clinicopathologic, immunohistochemical, and molecular study of a hitherto unreported tumor. 1531 25

A cohort of patients with intraductal growth-type intrahepatic cholangiocarcinoma (IG-ICC) and its precursor lesions, collectively termed intraductal papillary neoplasm of the liver (IPNL), was characterized with respect to demographics, clinical manifestations, perioperative management, long-term survival, and molecular features associated with carcinogenesis. A total of 122 patients with IPNL types 1 through 4, 108 patients with non-IG-ICC and 210 patients with hepatolithiasis alone were studied. Expression of CDX2, TFF1, MUC1, MUC2, MUC5AC, EGFR, and p53 was determined by using immunohistochemistry. Females predominated in those with hepatolithiasis alone and IPNL. The mean age of patients with hepatolithiasis alone was 6 to 8 years younger than that of those with IPNL. The association with hepatolithiasis in patients with IPNL types 1 and 2, IPNL types 3 and 4, and non-IG-ICC was 100%, 79%, and 64%, respectively. Mucobilia, anemia, and elevated serum carcinoembryonic antigen levels were helpful in distinguishing IG-ICC and its precursor lesions. The mean survival of patients with IPNL type 3, IPNL type 4, and non-IG-ICC was 55.5 months, 36.9 months, and 15.8 months, respectively. The incidence of expression of CDX2 and TFF1 was maximal in IPNL type 3. Expression and cellular distribution of MUC2 and CDX2 were similar. MUC5AC was strongly expressed in all patients with IPNL; EGFR and p53 were rarely expressed in patients with IPNL. In conclusion, hepatolithiasis appears to be a precipitating factor in the development of IPNL. Signs of mucobilia were specific for the diagnosis of IPNL. Expression of CDX2 and MUC2 are helpful in differentiating IPNL and non-IG-ICC. Significant differences in survival associated with the various lesions studied warrants a more aggressive surgical strategy in their management.
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PMID:Characterization of intrahepatic cholangiocarcinoma of the intraductal growth-type and its precursor lesions. 1611 40

Rectal adenocarcinoma with diffuse oncocytic features is a very rare lesion, having been reported only once in the English literature. We describe a case of oncocytic adenocarcinoma of the rectum, associated with a villous adenoma, arising on a 66-year-old man. On histological examination, the adenocarcinoma was composed of neoplastic glands lined by a strongly eosinophilic, granular epithelium that deeply infiltrated the rectal wall. Some basophilic calcifications were present in the gland lumina. Superficially, a villous adenoma with high-grade dysplasia was evident; adenomatous cells showed focal eosinophilic changes, consisting of a large granular cytoplasm, an oval atypical nucleus, and a prominent nucleolus. Immunohistochemically, neoplastic glands reacted strongly with antimitochondria antibody, carcinoembryonic antigen, cytokeratin 20, p53, and CDX2. Molecular alterations observed in oncocytic changes and their significance with regards to neoplastic transformation are briefly discussed.
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PMID:Oncocytic adenocarcinoma of the rectum arising on a villous adenoma with oncocytic features. 1645 Jan 20

Micropapillary carcinoma (MC) has been well described in other organs, including breast, urinary bladder, lung, ovary, and salivary gland, but has not been described in the large intestine. We compared the clinicopathologic and immunohistochemical findings of MC with those of conventional adenocarcinoma in the large intestine. Fifty-five cases of adenocarcinoma with an MC component were identified among 585 consecutive cases of colorectal cancer at the Asan Medical Center between January 2003 and June 2004 and were compared with 119 cases of conventional adenocarcinoma of colorectum without an MC component. Arrayed tissue blocks were constructed and immunostained for cytokeratin 7 and 20 and CDX2. We also compared the results of MLH-1, MSH-2, p53, and carcinoembryonic antigen immunostainings between the 2 groups. The grade of both MC and conventional adenocarcinoma was mostly moderately differentiated. The proportion of MC ranged from 5% to 80%. The presence but not extent of MC in the primary tumors was associated with more frequent lymphovascular invasion and lymph node (LN) metastases, a greater mean number of positive LNs, and a higher tumor stage with more frequent distant metastases, compared with conventional adenocarcinoma (P < .05). Cytokeratin 7 staining was occasionally observed in both MC (9.1%, 5/55 cases) and conventional adenocarcinoma (13.4%, 16/119 cases). Although MLH-1 and CDX2 expression tended to be lower in conventional adenocarcinoma, none of the immunohistochemical results was significantly different between 2 groups. Recognition of MC component is important as MC appeared to be an aggressive variant of colonic adenocarcinoma and presented at a higher stage, with frequent lymphovascular invasion, LN metastasis, and distant metastasis, compared with conventional adenocarcinoma. The proportion of MC component did not impact the prognosis, and the immunoprofiles of MC were not significantly different from those of conventional adenocarcinoma.
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PMID:Invasive colorectal micropapillary carcinoma: an aggressive variant of adenocarcinoma. 1678 79

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.
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PMID:Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications. 1721 55

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. The lesions contain a tubular adenocarcinoma that seems to develop "hepatoid" features, but the relation between the tubular adenocarcinomatous and the hepatoid components remains unclear. We compared the cellular phenotypes of 23 cases of hepatoid adenocarcinoma of the stomach having tubular adenocarcinomatous components with 69 cases of non-hepatoid adenocarcinoma of the stomach. Afterward, we examined the expression of CDX2 and p53 in the tubular adenocarcinomatous and hepatoid components of hepatoid adenocarcinoma. Both components of hepatoid adenocarcinoma were classified into 4 phenotypic categories according to the immunohistochemical results for CD10, MUC2, MUC5AC, and MUC6. The complete intestinal phenotype (CD10+, MUC5AC-, MUC6-) was most frequently observed in the adenocarcinomatous and hepatoid components (61% and 65%, respectively). In contrast, no gastric phenotype (MUC5AC+, MUC6+, MUC2-, CD10-) was observed in any of the hepatoid adenocarcinoma components. The positivity for p53 protein in the adenocarcinomatous and hepatoid components was concordant. The expression of CDX2 with early differentiation and maintenance of intestinal epithelial cells was observed in all of the adenocarcinomatous components, whereas 9 of the 23 hepatoid components (39%) were negative for CDX2. These findings suggest that hepatoid adenocarcinoma arises from an adenocarcinoma with an intestinal phenotype and that its hepatoid component is in some way related to reduced CDX2 expression.
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PMID:Hepatoid adenocarcinoma of the stomach: histogenesis and progression in association with intestinal phenotype. 1732 Jan 50

Pyloric-gland type adenoma of the gallbladder is formed by proliferation of glands resembling pyloric glands, morphologically. No previous report has described the cellular phenotype and differentiation of pyloric-gland type adenoma of the gallbladder, using CD10 as a marker of proper biliary phenotype. Immunostainings were performed for mucin markers such as MUC5AC, human gastric mucin (HGM) for gastric foveolar type epithelium, MUC6, M-GGMC-1 for pyloric-gland type and MUC2 for intestinal goblet-cell type, and for CD10 as a proper biliary type marker on 58 pyloric-gland type adenomas of the gallbladder, as well as for p53, Ki-67 and CDX2. The percentage (X) of reactive cells in relation to the total number of tumor cells was estimated semi-quantitatively, and divided into four categories: X=0% (negative), 0%<X<10%, 10%<or=X<30%, and X>or=30%. CDX2 expression was considered to be positive when the percentage of positively stained cells was >or=10%. Out of the 58 pyloric-gland type adenomas, >or=30% of adenoma cells were positive for MUC5AC in 22 (38%) tumors, HGM in 29 (50%), MUC6 in 58 (100%), M-GGMC-1 in 54 (93%), MUC2 in none (0%), and CD10 in 20 (34%). MUC6 (P<0.001) and M-GGMC-1 (P<0.001) mucins were detected more frequently in pyloric-gland type adenomas, and CD10 expression was significantly decreased, compared with normal gallbladder epithelium (P=0.006). P53 overexpression was not found in any of the 58 tumors, including two adenomas with carcinomatous foci. The mean number of Ki-67-positive cells was 10.3+/-5.8%. CDX2 expression was judged as negative in all 58 pyloric-gland type adenomas. In pyloric-gland type adenomas of the gallbladder, expression of pyloric-gland type mucins was observed with a high frequency, whereas intestinal goblet-cell mucins were rarely seen. In addition, co-expression of gastric foveolar type mucins and CD10 was also demonstrated. Pyloric-gland type adenomas of the gallbladder show a differentiation toward pyloric glands in terms of immunohistochemistry, as well as morphology, accompanied by co-expression of gastric foveolar and native biliary phenotypes.
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PMID:Co-expression of gastric and biliary phenotype in pyloric-gland type adenoma of the gallbladder: immunohistochemical analysis of mucin profile and CD10. 1734 6


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