Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As an animal model for human inflammatory bowel disease and colorectal cancer, the cotton-top tamarin remains controversial. Demonstration of antigenic similarity to the human would enhance its validity. Using colonic extracts and washings, we compared binding of seven monoclonal antibodies reactive with bowel and cancer antigens in both tamarins and humans with inflammatory bowel disease. Additionally, telomerase activity was tested for. Expression of a mucin antigen specific to human cancer was increased in tamarin colonic washings as well as aminoproteoglycans and EGFR in tamarin extracts, as compared to those of humans with inflammatory bowel disease (P < 0.005). An adenoma-associated antigen and k-ras p21 protein were negative in the tamarin. A trend to greater telomerase activity exists in tamarins. The antigenic similarity validates this model for human inflammatory bowel disease and colorectal cancer. A trend to increased telomerase activity in tamarins is consistent with the greater predisposition to cancer in these animals.
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PMID:Gastrointestinal tract antigenic profile of cotton-top tamarin, Saguinus oedipus, is similar to that of humans with inflammatory bowel disease. 1125 47

EGFR (epidermal growth factor receptor), p53, and proliferative markers provide some clues as to the formation of several tumours. In this study the mechanism of the genesis of parathyroid adenomas was investigated using immunohistochemistry. Sections of parathyroid adenomas from 12 cases were stained using PCNA (proliferating cell nuclear antigen), EGFR, and p53 immunohistochemistry. Correlations between PCNA LI (labelling index), EGFR expression, p53 expression, age, serum parathormone, Ca and P levels, and tumour diameter were investigated. PCNA LI was 45.8+/-33.1 (mean+/-standard deviation) and all the cases were somewhat positive. Five cases (41.67 %) were EGFR positive. Maximum 10 % of the cells were positive in these cases. All the cases were p53 negative. There was a correlation between PCNA LI and serum parathormone level (r=0.607, p=0.036). According to these results, parathormone synthesis is high when the proliferative activity of parathyroid adenoma is high. Four of the five EGFR-positive patients were below 35 years of age. These data may indicate that formation of parathyroid adenoma in young patients is related to a mechanism involving EGFR. Absence of p53 expression suggests that p53 mutation is not a common component of parathyroid adenomas.
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PMID:EGFR and p53 expression and proliferative activity in parathyroid adenomas; an immunohistochemical study. 1184 29

Mitogen-inducible gene 6 (MIG-6) is located in human chromosome 1p36, a locus frequently associated with human lung cancer. MIG-6 is a negative regulator of epidermal growth factor (EGF) signaling, and we show that Mig-6 - like EGF - is induced by hepatocyte growth factor/scatter factor (HGF/SF) in human lung cancer cell lines. Frequently, the receptors for both factors, EGFR and Met, are expressed in same lung cancer cell line, and MIG-6 is induced by both factors in a mitogen-activated protein kinase-dependent fashion. However, not all tumor lines express MIG-6 in response to either EGF or HGF/SF. In these cases, we find missense and nonsense mutations in the MIG-6 coding region, as well as evidence for MIG-6 transcriptional silencing. Moreover, germline disruption of Mig-6 in mice leads to the development of animals with epithelial hyperplasia, adenoma, and adenocarcinoma in organs like the lung, gallbladder, and bile duct. These data suggests that MIG-6 is a tumor-suppressor gene and is therefore a candidate gene for the frequent 1p36 genetic alterations found in lung cancer.
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PMID:Evidence that MIG-6 is a tumor-suppressor gene. 1681 4

The proliferative activity of the tumor cells and the expression of tumor-associated genes and sex steroid hormone receptors were investigated immunohistochemically in ten cases of carcinoma ex pleomorphic adenoma (Ca-ex-PA) of the salivary glands. These were analyzed in benign and malignant components separately, and then were compared with ten cases of the other malignant tumors [adenocarcinomas, not otherwise specified (ACN) and salivary duct carcinomas (SDC)] and ten cases of pleomorphic adenomas (PA). The results obtained in this study were as follows: (1) malignant component of Ca-ex-PA showed a higher incidence of PCNA and Ki67 than benign component of Ca-ex-PA. A significant difference between benign component of Ca-ex-PA and PA was not observed. (2) A significant difference in the incidence of p53, c-erbB-2, EGFR overexpression was observed only between malignant component of Ca-ex-PA and benign component of Ca-ex-PA. (3) The incidence of PCNA, Ki67, p53, c-erbB-2 overexpression in malignant component of Ca-ex-PA showed the highest data among the four groups. These results suggest that Ca-ex-PA acquired the particular biological behavior in contrast to the other salivary neoplasms in the long-standing process while PA undergoes malignant transformation.
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PMID:Carcinoma ex pleomorphic adenoma of the salivary gland: an immunohistochemical study. 1731 Mar 48

Hyperparathyroidism (pHPT) is a relatively frequent endocrinopathy, however, the molecular mechanisms of its etiology remain poorly understood. This disorder is mainly associated with benign tumours (adenoma) and hyperplasia of the parathyroid, hence, the focus is directed also to genes that are likely to be involved in carcinogenesis. Among such genes are ErbB/Her family genes already used in diagnosis of other tumours (e.g., breast carcinoma) and reported also to play a role in development of endocrine lesions. So far, ErbB-1/Her-1/EGFR expression has been detected in pHPT-associated adenomas and hyperplasia as opposed to no expression in normal parathyroid tissue. Moreover, losses or gains of the fragments of chromosomes where ErbB/Her genes are located have been reported. In this study, the gene dosage of ErbB/Her family genes were determined for the first time in parathyroid adenomas, hyperplasia and morphologically unchanged tissue in order to establish their putative role in the development of the disease. Genomic DNA was isolated from 33 patients with sporadic hyperparathyroidism and the gene copy numbers were assessed using real-time PCR. The ErbB/Her genes' profile was unaltered in most of the examined samples. Two low-level amplifications of ErbB-1/Her-1/EGFR gene, two deletions of ErbB-2/Her-2, and six deletions of ErbB-4/Her-4 were found. The ErbB-3/Her-3 gene remained unaffected. No correlation with clinical parameters was found for any gene. Both the low number of alterations and a lack of their associations with clinical parameters exclude the prognostic value of the ErbB/Her genes family in parathyroid tumourigenesis. Nevertheless, the ErbB-4/Her-4 deletions seem to be interesting for further investigations, especially in the context of PTH secretion.
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PMID:The profile of ErbB/Her family genes copy number assessed by real-time PCR in parathyroid adenoma and hyperplasia associated with sporadic primary hyperparathyroidism. 1925 47

Appendiceal mucinous neoplasms have been the focus of considerable debate in recent years. We histologically classified 70 appendiceal mucinous neoplasms into three categories: 32 mucinous adenoma, 23 mucinous neoplasm of uncertain malignant potential, and 15 mucinous adenocarcinomas. Immunohistochemistry was performed for 24 proteins in different functional categories, specifically, oncogenic proteins (bcl-2, beta-catenin, CEA, C-erbB2, c-kit, Cox-2, Cyclin D1, EGFR, Ki-67, NF-kappaB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell-cycle regulators (p21, p27, p16), and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). Our data showed that 9 out of the 24 proteins were more frequently altered in the mucinous adenocarcinoma group than in the mucinous adenoma group (P<0.05), including beta-catenin (13% in mucinous adenoma vs 60% in mucinous adenocarcinoma), CyclinD1 (44 vs 87%), Ki-67 (high labeling index: 31 vs 67%), NF-kappaB (19 vs 60%), VEGF (16 vs 87%), E-cadherin (0 vs 47%), p53 (6 vs 40%), MUC2 (9 vs 67%), and MUC5AC (3 vs 40%). The distinct immunoexpression profile of mucinous neoplasm of uncertain malignant potential was placed between those of mucinous adenoma and mucinous adenocarcinoma (P<0.05). Moreover, the mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma categories displayed differences in terms of the number of altered markers among the nine proteins (P<0.05; mean 1.4 vs 2.6 vs 5.5, respectively). In mucinous adenocarcinoma, the p53 status was related to disease-free survival and overall survival of patients (P<0.05, both). NF-kappaB status and the number of altered protein markers made statistically marginal impacts on disease-free survival; also beta-catenin loss, on overall survival of patients. In conclusion, protein immunoexpression profiles may facilitate the classification of appendiceal mucinous neoplasms. In our study, the three tumor categories of mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma exhibited distinct immunoexpression profiles. Five and more altered protein markers, p53 overexpression, NF-kappaB positivity, and beta-catenin loss were predictive factors of adverse clinical outcomes in appendiceal mucinous adenocarcinomas.
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PMID:Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors. 1944 92

Histologic grade is a significant predictor of outcome in salivary gland carcinomas. We underlined some newly recognized findings in grading: (i) evidence of high grade anaplastic transformation, occurring either at initial presentation or at relapse, is correlated with the clinical outcome; (ii) extracapsular invasion of carcinoma ex pleomorphic adenoma should be measured because it is now a known prognostic marker; (iii) the MIB-1 proliferative index is the most useful immunohistochemical marker for prognosis of all salivary gland carcinomas. In recent years, specific chromosomal translocations have been reported in some salivary glands tumors. The PLAG1 and HMGA2 gene translocations have so far been identified only in pleomorphic adenomas, and their detection may potentially aid in diagnosis. The mucoepeidermoid carcinoma translocated 1--mastermind like gene family (MECT1-MAML2) translocation, characterizing mucoepidermoid carcinoma, is also a prognostic marker. Newly recognized entities are summarized with special interest on differential diagnosis pitfalls: oncocytic mucoepidermoid carcinoma, sclerosing mucoepidermoid carcinoma with eosinophilia, sclerosing polycystic adenosis, lymphadenoma, lipoadenoma, newly recognized morphological variants of epithelial-myoepithelial carcinoma, cribriform adenocarcinoma of the tongue, signet ring adenocarcinoma of minor salivary gland. Specific chromosomal translocations and latest knowledge of the molecular mechanisms responsible for salivary glands oncogenesis (Epidermal Growth Factor Receptor [EGFR], phosphorylated AKT, topoisomerase II alpha, p27, Stat 3, maspin) should pave the way toward future targeted therapies.
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PMID:[2009 update in salivary gland tumoral pathology]. 1990 Jun 33

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer deaths worldwide. Proper classification and early identification of HCC and precursor lesions is essential to the successful treatment and survival of HCC patients. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into three subgroups: those with mutant TCF1/HNF1 alpha gene, those with mutant beta-catenin, and those without mutations in either of these loci. Hepatic adenomas with alpha-catenin mutations have a significantly greater risk for malignant transformation in comparison with the other two subgroups. Telangiectatic focal nodular hyperplasia has now been reclassified as telangiectatic adenoma due to the presence of non-random methylation patterns, consistent with the monoclonal origin which is similar to hepatic adenoma and HCC. HCC precursor lesions demonstrate unique molecular alterations of HSP70, CAP2, glypican 3, and glutamine synthetase that have proven useful in the histologic diagnosis of early HCC. Though specific genetic alterations depend on HCC etiology, the main proteins affected include cell membrane receptors (in particular tyrosine kinase receptors) as well as proteins involved in cell signaling (specifically Wnt/beta-catenin, Ras/Raf/MEK/ERK and PI3K/Akt/mTOR pathways), cell cycle regulation (i.e. p53, p16/INK4, cyclin/cdk complex), invasiveness (EMT, TGF-beta) and DNA metabolism. Advances in gene expression profiling have provided new insights into the molecular genetics of HCC. HCCs can now be stratified into two clinically relevant groups: Class A, the low survival subclass (overall survival time 30.3+/- 8.02 months), shows strong expression signatures of cell proliferation and antiapoptosis genes (such as PNCA and cell cycle regulators CDK4, CCNB1, CCNA2, and CKS2) as well as genes involving ubiquitination and sumoylation; Class B, the high survival subclass (overall survival time 83.7 +/-10.3 months), does not have the above expression signature. In fact, insights into HCC-specific alterations of signal transduction pathways and protein expression patterns have led to the development of new therapeutic agents with molecular targets such as EGFR, VEGF, or other multi-kinase inhibitors. In the future, these specific molecular alterations in HCC can potentially serve as diagnostic tools, prognostic markers, and/or therapeutic targets with the potential to alter clinical outcomes.
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PMID:Molecular genetics of hepatocellular neoplasia. 2018 87

Individual colorectal adenomas have different propensities to progress to invasive disease. In this study, we explored whether these differences could be explained by gene copy number alterations. We evaluated 18 adenomas of patients without synchronous or subsequent carcinoma (6.5 years follow-up), 23 adenomas of carcinoma patients, and 6 related carcinomas. All samples were measured for their DNA ploidy status. Centromere probes for chromosomes 17 and 18, as well as gene-specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by multicolor fluorescence in situ hybridization. An increased genomic instability index of CEP17, SMAD7, and EGFR, as well as TP53 deletions and MYC amplifications defined adenomas of patients with synchronous carcinoma (P<0.05). Diploid NCOA3 signal counts were associated with longer adenoma recurrence-free surveillance (P=0.042). In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (P<0.05). Furthermore, aberrations of NCOA3, MYC, and RAB20 were associated with histopathologically defined high-risk adenomas (P<0.05). RAB20 amplifications were also correlated with high-grade dysplastic adenomas (P=0.002). We conclude that genomic instability in colorectal adenomas is reflected by EGFR, MYC, NCOA3, and RAB20 amplifications that do correlate with histomorphological features and are indicative for adenoma recurrence and the presence of synchronous carcinomas.
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PMID:Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma. 2110 17

Similar to the adenoma-carcinoma sequence of colorectal cancer, lung adenocarcinoma is thought to follow a linear multistep progression, in which a precursor lesion progresses to adenocarcinoma in situ, which is followed by invasive adenocarcinoma. However, lung adenocarcinoma can no longer be considered as a single type of tumor but rather a group of distinct subsets of tumors that arise from different molecular pathways. Consistent with this concept, recent findings revealed that this linear progression might not occur in all lung adenocarcinomas. First, according to the molecular classification based on expression profiling, lung cancer can be divided into at least two subsets; precancerous and in situ lesions share characteristics of molecular expression and clinical features with only one of the two subsets, suggesting that the linear progression is only applicable to the subset in the molecular classification. Second, when EGFR and KRAS were examined based on the progression steps, the mutation rate of KRAS was disproportionally distributed; however, according to the progression schema, gene alterations should be evenly accumulated along the entire progression. Third, by means of comparative genomic hybridization analysis, some adenocarcinoma in situ revealed gene alterations discontinuous to invasive adenocarcinoma. Finally, there were some clinical observations that support that some lesions escape from the progression. In this review, we hypothesize a novel scenario for the progression of lung adenocarcinoma, which does not support a linear progression schema.
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PMID:Do all lung adenocarcinomas follow a stepwise progression? 2170 7


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