Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer

Yamamichi, Keigo; Uehara, Yoshio; Kitamura, Naomi; Nakane, Yasushi; Hioki, Koshiro

doi:10.1002/(sici)1097-0215(19980619)79:3<256::aid-ijc8>3.0.co;2-o

Cited by 43 publications

(19 citation statements)

References 16 publications

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“…Variant CD44v6 expression has often been associated with the intestinal type of Laurén and lymphatic spread of the tumour 8,10 , 15,24 , 25 . However, the claimed prognostic value of v6 expression 26,27 remains unconfirmed by others 9,10 . Expression of variant CD44v5 seems also to be associated with the intestinal type of cancer, high differentiation grade, deep level of invasion and poor prognosis in gastric cancer in a study by Müller et al ., 9 while variant CD44v9 expression is related to depth of tumour invasion and nodal metastasis 7 .…”

Section: Discussionmentioning

confidence: 99%

Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer

Setälä

Lipponen²,

Tammi

et al. 2001

Histopathology

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To study the controversial role of transmembrane glycoprotein CD44 as a moderator of tumour spread and as a prognostic factor in gastric cancer. The expression of all CD44 forms and that with exon v3 was assessed in 198 stage I‐IV gastric adenocarcinomas using immunohistochemistry. CD44 expression was found in 72% and CD44v3 in 55% of the cases. The intensity of CD44 expression was associated with the level of invasion and with hyaluronan expression, while the frequency of CD44 positive cells was not significantly related to any of the clinical or histological features of the tumours. CD44v3 expression failed to show any association with the clinical or histological variables examined. Neither total CD44 nor CD44v3 expression affected survival. The most important prognostic factors in this cohort were the level of invasion, lymph node status, tumour size and vascular or perineural invasion. Changes in CD44 or CD44v3 expression level do not predict tumour spread or patient survival in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer

Setälä

Lipponen²,

Tammi

et al. 2001

Histopathology

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“…In addition, increased expression of FXYD5, a CDH1 inactivator, has been significantly associated with poor prognosis (8,9). TACSTD1 down-regulation and CD44v6 upregulation have been also suggested to be prognostic markers for gastric cancer (5,6).…”

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confidence: 99%

Clinical Significance of CD99 Down-Regulation in Gastric Adenocarcinoma

Lee

Kim

Wang

et al. 2007

Clinical Cancer Research

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Purpose: CD99 is a cell adhesion molecule associated with human tumors. The aim of the present study was to characterize its role in the development and progression of human gastric adenocarcinoma. Experimental Design: The expression of CD99 was investigated in 283 gastric adenocarcinomas and related lesions and 9 gastric carcinoma cell lines.We also analyzed the methylation status of CD99 gene by using methylation-specific PCR and examined loss of heterozygosity (LOH) of this gene locus by using an intragenic marker. Moreover, we assessed whether SP1, a positive transcription factor for CD99, is expressed in these samples. Results: We found that the decreased expression of CD99 was strongly associated with poor survival and unfavorable clinicopathologic variables. Promoter region methylation (15 of 89, 16.9%) and LOH (21 of 74, 28.4%) were observed and significantly associated with CD99 down-regulation (P < 0.05). In addition, most of the gastric adenocarcinoma cases with CD99 down-regulation had reduced expression of SP1 (47 of 103, 45.6%; P < 0.01). This relationship between CD99 and SP1was consolidated by using SP1small interfering RNA transfection experiment and CD99 promoter luciferase assay. Furthermore, we showed that CD99 down-regulation was associated with proliferation and migration in gastric carcinoma cell line. Conclusion: These observations suggest that CD99 down-regulation is a critical event in the progression of gastric adenocarcinoma, and CD99 promoter methylation, CD99 LOH, and SP1 down-regulation were responsible for the down-regulation of CD99.

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“…In gastric cancer patients, prognostic markers, including erb-b2 receptor tyrosine kinase 2 (ERBB2) (26,27), CD44 (28,29) and matrix metallopeptidase 12 (30) have been reported. Additionally, a previous study by the present team demonstrated that the expression of the microRNAs mir-20b and mir-150 may be a prognostic marker for undifferentiated gastric cancer (1).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

et al. 2016

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Abstract. Recent studies have shown constitutive activation of the Notch signaling pathway in various types of malignancies. However, it remains unclear whether this signaling pathway is activated in gastric cancer. In the present study, the aim was to investigate the role of Notch signaling in gastric cancer by investigating the subcellular localization of Notch-associated proteins in tissue samples from gastric cancer patients. Samples were obtained from 115 gastric cancer patients who had undergone surgery at the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science without pre-operative chemotherapy or radiation. Subsequently the correlation between translocation of NOTCH1 intracellular cytoplasmic domain (NICD) into the nucleus (as measured by immunostaining) and survival in gastric cancer patients after surgery was investigated. The results were analyzed in reference to the patients' clinicopathological characteristics and the effects of these results on patient prognosis were determined. Significant correlations were observed between NICD nuclear localization and clinicopathological characteristics, such as tumor status (T factor), lymph node status (N factor), pathological stage and differentiation status. No significant correlations were observed between NICD nuclear localization and age, gender, tumor location, vein invasion or lymphatic invasion. Patients with >30% of cancer cell nuclei positively stained for NICD (as revealed by immunostaining) were associated with a significantly shorter survival following surgery than patients with <30% NICD-positive cancer cell nuclei (log-rank test, P=0.0194). Univariate analysis revealed that among the clinicopathological factors examined, T factor [risk rate (RR)=10.870; P=0.0016], N factor (RR=41.667; P=0.0003), lymphatic invasion (RR=13.158; P=0.0125), vein invasion (RR=25.000; P= 0.0019) and translocation of NICD to the nucleus (RR=3.937; P=0.0312) were all identified to be statistically significant prognostic factors. However, multivariate analysis revealed that translocation of NICD to the nucleus was not independently associated with an unfavourable prognosis in patients with gastric cancer. The present results suggest that NOTCH1 acts as an oncogene in gastric cancer. It is hypothesized that translocation of NICD into the nucleus may be used as a therapeutic target in gastric cancer.

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Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer

Cited by 43 publications

References 16 publications

Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer

Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer

Clinical Significance of CD99 Down-Regulation in Gastric Adenocarcinoma

Clinical significance of NOTCH1 intracellular cytoplasmic domain translocation into the nucleus in gastric cancer

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