Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology and p53 gene alteration

Nishikura, Ken; Watanabe, Hidenobu; Iwafuchi, Mitsuya; Fujiwara, Takanori; Kojima, Kazuko; Ajioka, Yoichi

doi:10.1007/s10120-003-0249-0

Cited by 88 publications

(79 citation statements)

References 12 publications

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“…Nishikura et al [9] reported concordant mutational status of the p53 gene between the adenocarcinoma component and NEC component in 73.3 % (11 of 15) of gastric AdenoNECs and no mutation in gastric NET (0 of 5), supporting our hypothesis despite the limited number of samples. Further study with molecular analysis or gene microarray analysis with many Fig.…”

Section: Discussionsupporting

confidence: 85%

“…However, the tumorigenesis of gastric NEC remains unclear, although gastric NECs have been reported to frequently exhibit an adenocarcinomatous component, and a tumorigenic pathway of gastric NEC arising from a coexisting adenocarcinomatous component has been proposed [8,9]. To confirm this hypothesis, we investigated the expression of mucin core proteins and CDX2 in gastric neuroendocrine neoplasms.…”

Section: Introductionmentioning

confidence: 97%

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Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis

et al. 2013

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Background Gastric neuroendocrine neoplasia has been classified as neuroendocrine tumor (NET), a less-malignant type, and neuroendocrine carcinoma (NEC), a moremalignant type. We investigated phenotypic expression profiles to clarify the differences between NET and NEC in terms of histopathology and carcinogenesis. Methods We assayed 86 cases of gastric neuroendocrine neoplasms (NET G1, n = 25; NET G2, n = 9; NEC, n = 52), using six exocrine markers (MUC5AC, human gastric mucin, MUC6, M-GGMC-1, MUC2, and CDX2). Results NEC frequently coexisted with adenocarcinomatous components (75 %; 39 of 52) and the majority (71.8 %; 28 of 39) showed intraglandular endocrine cell hyperplasia, although no cases of NET showed adenocarcinomatous components. Mucin phenotype significantly differed between NET and NEC; none of NET cases expressed any exocrine markers other than CDX2, although the majority of NEC (86.5 %; 45 of 52) expressed at least one or more exocrine markers with various positive rates for each marker (range, 8.2-74.0 %). Each NEC component showed only the phenotype expressed in the adenocarcinomatous component in the same tumor. Furthermore, double immunohistochemistry revealed dual expression of CDX2 and chromogranin A in half the NEC cases (23 of 46). Conclusions These data suggest that gastric NETs (G1 and G2) and NECs have different processes of carcinogenesis, and gastric NECs may be generated from preceding adenocarcinomas.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 97%

Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis

et al. 2013

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“…Gastric NECs are considered to arise predominantly from endocrine precursor cell clones that develop in the preceding adenocarcinoma component rather than ECL cells. These clones transform into NEC lesions during rapid clonal expansion, while NEC tumors develop rapidly in the submucosal and deeper layers (4,5). In the present case, the endoscopic findings showed a reddish area of erosion, which corresponded to the adenocarcinoma component, and endoscopic ultrasonography revealed a hypoechoic mass in the submucosal layer, which reflected the NEC component.…”

Section: Discussionsupporting

confidence: 46%

Gastric Mixed Adenoneuroendocrine Carcinoma with a Good Prognosis

et al. 2014

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A flat, elevated lesion measuring 5 mm in diameter was found in the gastric body of an 80-year-old man. A biopsy showed moderately differentiated adenocarcinoma, and endoscopic ultrasonography revealed a hypoechoic mass located in the submucosa. Endoscopic submucosal dissection was subsequently performed, and a pathological examination revealed a tumor composed of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration. The pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma (MANEC). An additional gastrectomy procedure was performed, and no recurrence was noted for at least three years. This case is interesting with respect to the carcinogenesis of endocrine cell carcinoma and MANEC.

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“…On the other hand, it is well known that p53 mutations are the most common genetic alterations in ordinary GC [29][30][31]. Nishikura et al [4] showed that p53 overexpression was observed in 58.8% of gastric ECs, but not in gastric carcinoid tumors. Expression of p53 was associated with a high degree of cell proliferation (Ki-67-positive nuclear cells) and this marker also was able to predict a shorter survival time [5].…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that gastric EC predominantly arises from endocrine precursor cell clones occurring in preceding adenocarcinoma components, which transform into EC during rapid clonal expansion [4]. This hypothesis was supported by correlations between the pattern of p53 protein overexpression and the concordance of common p53 mutational patterns between the gastric EC and adenocarcinoma components.…”

Section: Introductionmentioning

confidence: 94%

Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute

et al. 2012

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Background Gastric endocrine carcinoma (EC) is an uncommon tumor of the stomach and the clinical features are not well known. Additionally, the classification and staging systems of this tumor are not yet unified worldwide. In this study, we reviewed 27 patients with gastric EC to evaluate the clinicopathological characteristics of this tumor. Methods We retrospectively reviewed 27 patients with gastric EC among 6466 patients who had undergone gastrectomy between 1986 and 2008 at our institute. Clinicopathological features including immunohistochemistry of Ki-67 were investigated to evaluate the malignant potential of the tumor. Furthermore, survivals were compared between the 7th edition of the International Union Against Cancer (UICC)-TNM (7th TNM) classification for gastric cancer (GC) and the new TNM classification for foregut neuroendocrine tumors (NET). Results The median survival of the patients was 19.0 months. The 5-year survival rate was 100% in pathological stage (pStage) I, 40% in pStage II, 38% in pStage III, and 11% in pStage IV according to the 7th TNM classification for GC. Survivals by stage showed great difference between the 7th TNM classification for GC and the new TNM classification for foregut NET, but each system correlated with survival. The Ki-67 labeling index was more than 20% in most of the patients. Univariate analysis revealed that maximum tumor diameter, tumor depth, lymph node metastasis, lymphatic invasion, pStage, and curability had significant correlations with survival. Conclusion Early detection and curative operations are essential for improving the prognosis of gastric EC. However, some adjuvant chemotherapies are required for advanced-stage tumors. Classification and staging systems may need to be unified worldwide for further analysis.

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Carcinogenesis of gastric endocrine cell carcinoma: analysis of histopathology and p53 gene alteration

Cited by 88 publications

References 12 publications

Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis

Mucin phenotype expression of gastric neuroendocrine neoplasms: analysis of histopathology and carcinogenesis

Gastric Mixed Adenoneuroendocrine Carcinoma with a Good Prognosis

Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute

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