Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations

Yamazaki, Kaoru; Tajima, Yusuke; Makino, Reiko; Nishino, Nobukazu; Aoki, Shigeo; Kato, Masanori; Sakamoto, Masaaki; Morohara, Koji; Kaetsu, Tsutomu; Kusano, Mitsuo

doi:10.3748/wjg.v12.i24.3803

Cited by 33 publications

(32 citation statements)

References 34 publications

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“…b P ¼ 0.0493 (advanced adenocarcinoma of the gastric cardia vs advanced adenocarcinoma of the distal stomach) and P ¼ 0.0363 (total adenocarcinoma of the gastric cardia vs total adenocarcinoma of the distal stomach). Table 5 Genetic alterations in differentiated-type adenocarcinoma of the gastric cardia and distal stomach whereas I-phenotype tumours have been reported to account for 10.1% of all undifferentiated-type tumours (Tatematsu et al, 1990;Egashira et al, 1999;Tajima et al, 2001aTajima et al, , b, 2004Yamazaki et al, 2006). These previous data suggest that gastric carcinomas may arise from various types of gastric mucosa, although differentiatedtype tumours have generally been considered to arise from gastric mucosa with intestinal metaplasia and undifferentiated-type tumours to arise from ordinary gastric mucosa without intestinal metaplasia (Lauren 1965;Nakamura et al, 1968).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of the APC gene in exon 15, codons 1260 -1596 and the K-ras gene in codons 12 -13 were detected by fluorescence-based PCR-single-strand conformation polymorphism (PCR-SSCP) analysis using primers described previously (Hiyama et al, 2002;Lee et al, 2002;Yamazaki et al, 2006). After amplification, the PCR products from each sample were examined for mutations of the APC or K-ras gene, by fluorescence-based single-strand conformation polymorphism analysis using the ALFexpress DNA sequencer (Amersham Biosciences, NJ, USA) with a cooling bath.…”

Section: Gene Mutation Analysismentioning

confidence: 99%

“…Mutations of the p53 gene in the exon 5 -8 region were detected by fluorescence-based PCR-SSCP analysis using capillary electrophoresis (Makino et al, 2000;Yamazaki et al, 2006). The nucleotide sequences of the primers have been described previously.…”

Section: Gene Mutation Analysismentioning

confidence: 99%

“…Mutations were detected by electrophoresis using a 3100 Genetic Analyzer (Applied Biosystems, CA, USA). The peak pattern was analysed using the QUISCA software (Konishi et al, 2004;Yamazaki et al, 2006). The nucleotide sequences of the DNA fragments with shifted peaks were determined using the Genetic Analyzer 310 with a BigDye Terminator (Applied Biosystems).…”

Section: Gene Mutation Analysismentioning

confidence: 99%

“…The primers and PCR conditions have been described elsewhere (Konishi et al, 2004;Yamazaki et al, 2006). The samples were subjected to capillary electrophoresis on an ABI 3100 Genetic Analyzer using the Genescan Analysis software (Applied Biosystems).…”

Section: Msi Analysismentioning

confidence: 99%

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Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

et al. 2007

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Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P ¼ 0.0006 and 72.2 vs 55.3%, P ¼ 0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P ¼ 0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P ¼ 0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P ¼ 0.0402 and 51.5 vs 84.6%, P ¼ 0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P ¼ 0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Gene Mutation Analysismentioning

confidence: 99%

Section: Gene Mutation Analysismentioning

confidence: 99%

Section: Gene Mutation Analysismentioning

confidence: 99%

Section: Msi Analysismentioning

confidence: 99%

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Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

et al. 2007

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Correlation of Microsatellite Instability at Multiple Loci With Long-term Survival in Advanced Gastric Carcinoma

et al. 2009

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Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum

Matsubara

Sekine

Kushima

et al. 2013

The Journal of Pathology

109

114

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Gastric and duodenal adenomas exhibit a significant morphological and phenotypical diversity and are classified into intestinal-type, foveolar-type and pyloric gland adenomas. We analysed the mutations in GNAS, KRAS, BRAF and CTNNB1 and the expressions of mismatch repair (MMR) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating GNAS mutations were found in 22 of the 35 pyloric gland adenomas (PGAs; 63%) but in none of the foveolar-type or intestinal-type adenomas or the adenocarcinomas. Fourteen PGAs (41%), two foveolar-type adenomas (9%), five intestinal-type adenomas (9%) and one adenocarcinoma (1%) had KRAS mutations. BRAF mutations were absent in all the adenomas and adenocarcinomas that were examined. CTNNB1 mutations were only found in two intestinal-type adenomas (4%). Notably, 13 of the 14 KRAS-mutated gastric and duodenal PGAs had concurrent GNAS mutations. The loss of the MMR proteins, which is indicative of microsatellite instability, was observed in one PGA (3%), 12 foveolar-type adenomas (52%), one intestinal-type adenoma (2%) and five adenocarcinomas (7%). These observations indicate that each histological subtype of gastric and duodenal adenomas has a distinct genetic background. In particular, the present study identified the frequent presence of activating GNAS mutations, which are often associated with KRAS mutations, as a characteristic genetic feature of PGAs of the stomach and duodenum.

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Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations

Abstract: The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors.

Cited by 33 publications

References 34 publications

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

Correlation of Microsatellite Instability at Multiple Loci With Long-term Survival in Advanced Gastric Carcinoma

Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum

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