Loss of Heterozygosity and Immunohistochemistry of Adenocarcinomas of the Esophagus and Gastric Cardia

Marsman, Willem A.; Birjmohun, Rakesh S.; Rees, Bastiaan P. van; Caspers, Eric; Johan, G.; Offerhaus, A.; Bosma, Piter J.; Jan, J.; Lanschot, B. van

doi:10.1158/1078-0432.ccr-04-0839

Cited by 11 publications

(7 citation statements)

References 41 publications

(40 reference statements)

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“…Investigation of loss of heterozygosity (LOH) is an important tool to detect potential losses of tumor suppressor genes which can characterize different kind of cancers. We and others tried to differentiate adenocarcinomas of the esophagus and gastric cardia according to their LOH pattern, but no significant differences could be identified between the two tumors [56,57]. While van Dekken et al found a significant difference at locus 14Q using comparative genomic hybridization [58], this could not be confirmed in other studies.…”

Section: Genetic Changesmentioning

confidence: 93%

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction

Marsman

Tytgat

Kate

et al. 2005

Journal of Surgical Oncology

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During the last few decades there has been an alarming rise in the incidence of tumors originating at the esophagogastric junction (EGJ) [1]. The reason for this is unknown. Tumors of the EGJ can be categorized in two types of cancer divided according to their anatomical origin: distal esophageal adenocarcinoma and adenocarcinoma of the gastric cardia. However, due to their location, in the transitional zone of the esophagus and stomach, there is constant debate about the proper classification, staging, and management of these tumors. The etiology of distal esophageal adenocarcinoma is clearly related to gastroesophageal reflux disease (GERD) and the development of a Barrett's esophagus [2]. The etiology of adenocarcinoma of the gastric cardia is less well understood. In the present paper, we will discuss the clinical characteristics and clinical management of esophagogastric tumors. Special attention will be given to differences and similarities of adenocarcinomas of the gastric cardia and distal esophagus.

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Section: Genetic Changesmentioning

confidence: 93%

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction

Marsman

Tytgat

Kate

et al. 2005

Journal of Surgical Oncology

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“…Scoring of immunohistochemistry was carried out for p53, 28 E-Cadherin, 29 TFF, 30 b-Catenin, 31 COX-2, 32 p16, 33 HuR, 34 C/EBP-b, 15 c-myc 35 and c-jun, as shown in Table 2.…”

Section: Scoringmentioning

confidence: 99%

Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

et al. 2006

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Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (< or = 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in gastric adenocarcinomas compared to non-neoplastic mucosa, and in light of studies showing reduced risk of gastric cancer in nonsteroidal anti-inflammatory drug users, we have chosen to investigate the expression of COX-2 and related molecules in 113 early-onset gastric cancers and compare it with 91 conventional gastric cancers, using tissue microarrays. These markers include molecules known to be important in conventional gastric carcinogenesis, such as E-Cadherin, p53, COX-2, Trefoil Factor-1 (TFF1), beta-catenin, p16 and c-myc; as well as molecules not yet described as being important in gastric cancer, such as the transcription factor c-jun, the COX-2 mRNA stabilizer HuR, and C/EBP-beta, a transcription factor for COX-2. All markers showed a statistically significant difference between early-onset gastric cancers and conventional gastric cancers, using a chi2 test. In particular, early-onset gastric cancers displayed a COX-2 Low, TFF1-expressing phenotype, whereas COX-2 overexpression and loss of TFF1 was found in conventional cancers, and this difference between early-onset gastric cancers and conventional cancers remained statistically significant when adjusted for location and histology (P<0.0001 and P = 0.002 respectively). We found that COX-2 overexpression correlates significantly with loss of TFF1 (P = 0.001), overexpression of C/EBP-beta (P<0.001) and cytoplasmic HuR (P = 0.016). COX-2 was significantly associated with p53 positivity (P = 0.003). Abnormalities in E-Cadherin correlated significantly with diffuse phenotype, whereas high expression of COX-2, loss of TFF1 and overexpression of C/EBP-beta correlated with the intestinal phenotype. Our results provide further evidence that early-onset gastric cancer exhibits a distinctive expression profile that may have practical implications.

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“…Most interestingly, the LOH events may be involved in the downregulation of the sFRP1 protein expression, as the percentage of LOH at locus D8S532 was significantly lower in the sFRP1 positive cases than in the negative cases (0.00% vs. 22.73%, P < 0.05). LOH has been suggested as a hallmark of the loci for tumorsuppressor genes (Lee et al, 2004;Marsman et al, 2004;Rutherford et al, 2006). When LOH occurs at a tumor suppressor gene that already has genetic lesions on one allele, this will lead to loss of function of this tumor suppressor gene, which can contribute to the development of cancer.…”

Section: Discussionmentioning

confidence: 99%

Involvement of genetic instability in the downregulation of sFRP1 in Chinese patients with hepatocellular carcinoma

Qiu

Zhou³

et al. 2010

The Anatomical Record

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Secreted frizzled-related protein 1 (sFRP1) is a new tumor suppressor based on recent researches, but the correlation of the genetic instability of sFRP1 gene with the clinicopathologic features of the hepatocellular carcinoma (HCC) has not been studied in Chinese people. In this study, 42 pairs of paraffin-embedded HCC and adjacent non-carcinoma tissues were examined for the loss of heterozygosity (LOH) and microsatellite instability (MSI) of two microsatellite markers D8S532 and D8S1722 located in the vicinity of the sFRP1 gene. Envision immunohistochemistry was used to assess the expression of sFRP1. We found that the reduced expression of the sFRP1 protein was frequently observed in Chinese patients with HCC, which may at least partially result from the genetic instability, especially LOH. The LOH-associated sFRP1 downregulation may play an important role in the development of HCC. Anat Rec, 293:2020Rec, 293: -2026Rec, 293: , 2010.

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Loss of Heterozygosity and Immunohistochemistry of Adenocarcinomas of the Esophagus and Gastric Cardia

Cited by 11 publications

References 41 publications

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction

Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction

Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

Involvement of genetic instability in the downregulation of sFRP1 in Chinese patients with hepatocellular carcinoma

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