Gastric and Intestinal Phenotypic Marker Expression in Early Differentiated-Type Tumors of the Stomach: Clinicopathologic Significance and Genetic Background

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

doi:10.1158/1078-0432.ccr-06-1339

Cited by 81 publications

(73 citation statements)

References 37 publications

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“…Muc5a, Muc6, and galactose are markers of gastric phenotype, whereas Muc2 and CD-10 are the intestinal subtype (43,65) . Similar to metaplasia, a subclassification of well-differentiated (Lauren's intestinal) cancer in phenotypes was established to better understand the biological x of these lesions (2,7,19,49,57,64,69) . This type is also known as intestinal cancer, presenting with different phenotypes based on mucin expression: gastric, intestinal, mixed, or indeterminate types (10,50) .…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

Hondo

Kishi

Safatle‐Ribeiro

et al. 2017

Arq. Gastroenterol.

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-Background -Endoscopic mucosal resection is still considered an accepted treatment for early gastric cancer for selected cases. Histopathologic criteria for curative endoscopic resection are intramucosal well-differentiated adenocarcinoma, lateral and deep margins free of tumor, no histological ulceration, and no venous or lymphatic embolism. A 5% local recurrence rate has been described even when all the above-mentioned criteria are met. On the other hand, antigen expression by tumoral cells has been related to the biological behavior of several tumors. Objective -To evaluate whether early gastric cancer mucin immunoexpression, p53 and Ki-67, can predict recurrence after endoscopic mucosal resection, even when standard histopathologic criteria for curative measures have been attempted. Methods -Twenty-two patients with early gastric cancer were considered to have been completely resected by endoscopic mucosal resection. Local recurrence occurred in 5/22 (22.7%). Immunohistochemical study was possible in 18 (81.8%) resected specimens. Patients were divided in two groups: those with and those without local recurrence. They were compared across demographic, endoscopic, histologic data, and immunohistochemical factors for MUC2, MUC5a, CD10, p53, and Ki-67. Results -Mucin immunoexpression allowed a reclassification of gastric adenocarcinoma in intestinal (10), gastric (2), mixed (4), and null phenotypes (2). Mixed phenotype (positive for both MUC2 and MUC5a) was found in 80% of cases in the local recurrence group, while the intestinal type (positive MUC2 and negative MUC5a) was found in 76.9% of cases without local recurrence (P=0.004). Other observed features did not correlate with neoplastic recurrence. Conclusion -The mixed phenotype of early gastric adenocarcinoma is associated with a higher probability of local recurrence after endoscopic mucosal resection.HEADINGS -Stomach neoplasms. Endoscopic mucosal resection. Gastric mucins.

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Section: Introductionmentioning

confidence: 99%

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

Hondo

Kishi

Safatle‐Ribeiro

et al. 2017

Arq. Gastroenterol.

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“…At present, the wide accepted pattern of GC development is gastritis-metaplasia-dysplasia-carcinoma sequence, proposed by Correa in 1988. The mechanisms of GC development are complicated, involving the alteration of oncogenes and tumor-suppressor genes, which form molecular genetic basis of malignant transformation and tumor progression (Tajima et al, 2006). Until now, lots of signal pathways regulating cell growth and cell apoptosis have been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Zhou¹,

Li²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

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“…Single or multiple mutations in genes related to growth control, apoptosis, invasion and metastasis form the molecular genetic basis of malignant transformation and tumor progression (5). Mounting evidence argues that the high mobility group box-B1 (HMGB1)-RAGE and protein kinase B (Akt) pathways play a crucial role in the development and progression of many malignant tumors, and have been considered as important therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo

et al. 2012

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Abstract. The high mobility group box-B1 (HMGB1)-receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. Ethyl pyruvate (EP), a potent inhibitor of HMGB1 release, can exert antitumor effects on the growth of gastric cancer. Therefore, it is necessary to observe the effects of EP on gastric cancer growth in vitro and in vivo. Human gastric adenocarcinoma tissues of different grades (N=45) were collected. The expression of HMGB1 and RAGE was evaluated immunohistochemically in biopsy samples. After SGC-7901 gastric cancer cells were treated with EP, the expression of HMGB1, RAGE, Akt, phosphorylated Akt (p-Akt) and some transcription factors was identified and the effects of EP on cell proliferation, invasion, cell cycle distribution and apoptosis were assessed. A subcutaneous xenograft tumor model was established, validating the effects of EP on tumor growth in vivo. The expression of HMGB1 and RAGE was respectively observed in 73.3 and 68.9% of the gastric adenocarcinoma tissues. The frequency of positive expression increased with the ascending grade of the tumor malignancy. EP decreased the expression of HMGB1, RAGE, Akt, p-Akt, Ki-67 and matrix metallopeptidase-9 (MMP-9), and increased the expression of p53. Moreover, EP could inhibit tumor cell proliferation and invasion, induce cell cycle arrest and apoptosis and slow the growth of xenograft tumors. In conclusion, HMGB1 and RAGE were strongly expressed in gastric adenocarcinoma, and EP administration inhibited gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways. EP may play a critical role in the treatment of cancer in conjunction with other therapeutic agents.

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Gastric and Intestinal Phenotypic Marker Expression in Early Differentiated-Type Tumors of the Stomach: Clinicopathologic Significance and Genetic Background

Cited by 81 publications

References 37 publications

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo

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