Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1990, Longacre and Fenoglio-Preiser introduced "serrated adenoma (SA)" combining architectural and cytological features of hyperplastic polyp and adenomatous epithelium. It has been reported that intramucosal carcinoma occurs in 10% of SAs. Although there have been many reports on SAs, its histogenesis and natural history still remain unknown. To clarify the genetic changes in SA, APC mutations in 28 SAs, 4 adenocarcinomas in/with SAs, 12 tubular adenomas (TAs) and 10 adenocarcinomas in/with TAs were evaluated in the present study. After polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) analyses, gene mutations were confirmed by direct sequencing. No APC mutation was detected in adenocarcinomas in/with SAs, and only one SA without adenocarcinoma (3.8%) was found to be positive for APC gene mutation, whereas the mutations were found in 66.7% of TAs and in 50% of adenocarcinomas in/with TAs. The frequency of APC gene mutation in SAs was significantly lower than that in control sporadic TAs. These findings suggest that SAs are genetically different from TAs.
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PMID:Infrequent APC mutations in serrated adenoma. 1131 65

Barrett esophagus, especially dysplastic Barrett mucosa, has been regarded as a preneoplastic lesion for esophageal adenocarcinoma. However, the etiology and pathogenesis of dysplasia and early adenocarcinoma in short- (SSBE) and long- (LSBE) segment Barrett esophagus have not been studied in detail. The aims of this study were to clarify clinicopathologic and genetic differences between high-grade dysplasia (HGD) and early adenocarcinoma in SSBE versus LSBE. We analyzed the clinicopathologic features from 47 patients (19 SSBE [<3 cm] and 28 LSBE [> or =3 cm]) with esophagectomy for HGD/T1 adenocarcinoma. Allelic losses on chromosomes 3p (FIHT), 5q (APC), 9p (p16), and 17p (p53) were compared in 12 HGD and 9 T1 tumors from 19 cases of SSBE and in 23 HGD and 15 T1 tumors from 28 cases of LSBE. Patients with SSBE were more likely to be smokers than were patients with LSBE (94.7% v 57.1%; P =.004). HGD or T1 tumors arising from SSBE were less likely to show adjoining nondysplastic Barrett mucosa than those from LSBE (73.6% v 100%; P =.02). LSBE more frequently showed a circumferential pattern of Barrett mucosa than did SSBE (96.4% v 47.3%; P =.0002). Chromosomal allelic losses on 3p, 5q, 9p, and 17p were detected in 19% (4 of 21), 43% (15 of 35), 40% (14 of 35), and 48% (16 of 33) of HGD, respectively, and 26% (5 of 19), 35% (8 of 23), 35% (8 of 23), and 57% (13 of 23) of T1 tumor, respectively. There were no significant differences in allelic loss of 3p, 5q, 9p, or 17p in HGD or T1 tumors from SSBE versus LSBE. These results suggest that both HGD and early adenocarcinoma in SSBE and LSBE may occur through similar genetic alterations, whereas there are some clinicopathologic differences between SSBE and LSBE. HUM PATHOL
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PMID:Clinicopathologic and molecular analysis of high-grade dysplasia and early adenocarcinoma in short- versus long-segment Barrett esophagus. 1133 63

Samples of Barrett metaplastic specialized epithelium (SE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) derived from 36 esophagectomy specimens were studied for loss of heterozygosity (LOH) in APC and MCC and for expression of APC protein. Of 18 cases that were heterozygous (informative) for APC, LOH was found in none of 14 SE samples, 2 of 8 LGD samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immunohistochemically, markedly reduced expression of APC protein (< 50% positive cells) was found in 3 of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17 cases informative for the MCC gene, LOH was detectable in 1 of 14 SE samples, none of 7 LGD samples, none of 9 HGD samples, and 4 of 16 CA samples. Allelic loss of APC and/or loss of APC protein expression occurs earlier in the metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC gene. The determination of alterations at APC or MCC would be of limited importance for the surveillance of patients with Barrett esophagus.
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PMID:Allelic loss involving the tumor suppressor genes APC and MCC and expression of the APC protein in the development of dysplasia and carcinoma in Barrett esophagus. 1133 78

Promoter hypermethylation is an important pathway for the repression of gene transcription in cancer. We investigated promoter hypermethylation of six genes, p16, APC, HIC-1, death-associated protein kinase (DAPK), O(6)-methylguanine-DNA-methyltransferase (MGMT), and E-cadherin, in uterine cervical carcinoma from 53 patients including 31 cases of squamous cell carcinoma (SCC) and 22 cases of adenocarcinoma (AC). Aberrant methylation of at least one of these genes was detected in 79% (42 of 53) of cases including 71% (22 of 31) of SCC and 91% (20 of 22) of AC cases. No aberrant methylation was detected in normal cervical tissue from 24 control hysterectomy specimens. There was no correlation between promoter hypermethylation at any gene and the presence of human papillomavirus-16 or -18 E7 DNA. In AC cases, promoter hypermethylation of the APC and HIC-1 genes was detected at a statistically significant higher frequency than in the SCC cases (APC, 60% versus 13%, P < 0.001; HIC-1, 63% versus 32%, P < 0.03). Conversely, promoter hypermethylation of p16 and DAPK was more common in SCC cases than in AC cases. Our results suggest that promoter hypermethylation is a frequent epigenetic event in cervical carcinoma. The pattern of gene promoter hypermethylation is distinctly different between AC and SCC. The absence of these epigenetic alterations in normal cervical tissue suggests that they may also be valuable as cancer markers.
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PMID:Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix. 1144 14

Germline mutations of the Adenomatous polyposis gene (APC) are responsible for Familial Adenomatous Polyposis (FAP), an inherited condition that predisposes to the development of hundreds to thousands benign adenomas in the colo-rectum. If not surgically removed, they inevitably progress into malignant adenocarcinoma. To date more than 450 germline mutations have been described allowing the establishment of genotype/phenotype correlation between the site and type of molecular defects and their morbid consequences. Authors reviewed their experience concerning 22 FAP affected patients and their 26 first degree relatives, in whom the mutational analysis of the APC gene had been carried out. Site and type of mutations were associated with clinical parameters (age of onset, rectal involvement, extracolonic manifestations, presence of colorectal cancer) and treatments. The impact of mutational analyses on the clinical approach could be very interesting in the future, modifying both surveillance programs and therapeutical choices.
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PMID:[Familial colonic polyposis: effect of molecular analysis on the diagnostic-therapeutic approach]. 1155 76

In 10 cases of Barrett adenocarcinoma, samples from 8 tumor areas (including superficial and deep from peripheral and central areas) and a regional lymph node metastasis were studied for amplification of c-myc, c-erbB-2, and EGFR. We analyzed loss of heterozygosity (LOH) at 3 loci (APC, MCC, and RB) and 2 anonymous microsatellite markers (D4S1652 and D18S474). We detected c-myc in variable fractions of tissue samples from 3 of 9 tumors; EGFR was amplified in 2 specimens from 1 tumor. One tumor demonstrated amplification of c-erbB-2 in all areas. LOH at the D4S1652, MCC, RB, APC, and D18S474 loci was found in 75% (3/4), 57% (4/7), 50% (4/8), 11% (1/9), and 0% (0/10) of informative cases, respectively. LOH generally was restricted to variable subpopulations of tumor cells within individual tumors. There was no obvious association of certain genetic alterations with topographically distinct tumor regions; however, superficial areas showed more frequent genetic alterations than areas from the deeply invading front. More aberrations were detected in the periphery than in the center. Barrett adenocarcinoma is characterized by marked intratumoral genetic heterogeneity, which must be considered when evaluating genetic alterations as indicators of response to therapy and prognosis.
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PMID:Intratumoral genetic heterogeneity in Barrett adenocarcinoma. 1193 30

We experienced an unusual case of duodenal adenocarcinoma associated with Peutz-Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on the presence of mucocutaneous pigmentation of the lip and fingertips, and colonic hamartomatous polyps. Abdominal computed tomography revealed a tumor in the third portion of the duodenum extending into the pancreas head. As the tumor was pathologically determined to be adenocarcinoma at the time of surgery, pylorus-preserving pancreaticoduodenectomy was performed. We carried out molecular analyses of this patient to examine the pathway of carcinogenesis in PJS. The tumor did not show somatic mutation of the APC and K-ras genes, which is a critical step for the adenoma-carcinoma sequence in colon cancer. Importantly, a germline mutation of the STK11 gene was detected at codon 281 delC in exon 6. Moreover, the tumor showed loss of heterozygosity of the 19p marker near STK11 and somatic mutation of the p53 gene. These findings suggest that STK11 is a tumor suppressor gene regulating the development of hamartomas, and that somatic mutation of p53 subsequently promotes gastrointestinal cancer at a later stage in PJS.
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PMID:Duodenal cancer in a patient with Peutz-Jeghers syndrome: molecular analysis. 1205 37

In the present study, we used 22 microsatellite markers flanking to or within 13 known or candidate tumor suppressor genes (TSGs) to detect loss of heterozygosity (LOH) in these chromosomal regions among 41 cases of non-small cell lung cancer, including 28 squamous cell carcinoma (SCC) and 13 adenocarcinoma (ADC). The studied TSGs comprised FHIT, VHL, APC, PRLTS, p16, IFNA, PTEN, p57, ATM, p53, BRCA1, DPC4 and DCC. Our data demonstrated frequent allelic losses of FHIT, p53, IFNA, VHL and p16 in both SCC and ADC. PTEN and ATM showed the least frequency of LOH, while no deletion of BRCA1 was detected in all tumor samples. LOH analysis of PRLTS was extended to 26 cases of ADC, which demonstrated significantly higher frequency of LOH than SCC. Our data indicated a possible correlation between specific TSG(s) and either histological type of lung cancer, and more attention should be paid to the PRLTS gene, which might play an important role in the development of ADC.
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PMID:Deletion of tumor suppressor genes in Chinese non-small cell lung cancer. 1212 91

The clinical differentiation between hereditary nonpolyposis colorectal cancer (HNPCC) and attenuated familial adenomatous polyposis (AFAP) is very difficult. The 62-yr-old proband presented with duodenal adenocarcinoma. His history of subtotal colectomy for colon cancer, the rarity of duodenal adenocarcinoma in the general population, and his family history of colon cancer made us suspect that he might have FAP. We investigated this family by obtaining medical records and performing gene analysis. The proband had only 10 adenomatous colon polyps when he underwent subtotal colectomy for the cancer, so classic FAP was excluded. His family history included rectal cancer in his brother at 69 yr of age, colon cancer in his mother at 75 yr, and colon cancer in one maternal cousin at 42 yr. Three months after we started to study this family, the proband's 32-yr-old son presented with rectal cancer. His family fulfilled the Amsterdam criteria for HNPCC, but AFAP could not be excluded. Upon gene testing, the proband was negative for APC gene germline mutation, which made AFAP highly unlikely. Moreover, high microsatellite instability (MSI) was detected in his adenomas and cancer tissues. The fulfillment of Amsterdam criteria, the exclusion of FAP and AFAP, and the high MSI established the diagnosis of HNPCC in this family. We also summarize the differences between FAP, AFAP, and HNPCC; extend the graphic description of the MSI mechanism; and propose a diagnostic strategy for HNPCC.
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PMID:Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report with review of the literature. 1213 43

Colorectal cancer affected approximately 135,000 people in the United States in 2001, resulting in 57,000 deaths. Colorectal cancer develops as the result of the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic epithelium to colon adenocarcinoma. The loss of genomic stability is a key molecular and pathophysiologic step in this process and serves to create a permissive environment for the occurrence of alterations in tumor suppressor genes and oncogenes. Alterations in these genes, which include APC, CTNNB1, K-RAS, MADH4/SMAD4, and TGFBR2, appear to promote colon tumorigenesis by perturbing the function of signaling pathways, such as the TGF-ss signaling pathway, or by affecting genes that regulate genomic stability, such as the mutation mismatch repair genes.
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PMID:Genetic and epigenetic alterations in colon cancer. 1214 55


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