Expression of CD44 Variant 6 and Lymphatic Invasion: Importance to Lymph Node Metastasis in Gastric Cancer

Kurozumi, Kazushi; Nishida, Toshirou; Nakao, Kazuyasu; Nakahara, Masaaki; Tsujimoto, Masahiko

doi:10.1007/s002689900481

Cited by 29 publications

(24 citation statements)

References 18 publications

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“…However, the direct role of CD44v in the metastatic process has remained obscure. It has been reported that CD44v6 in gastric cancer was related to tumor growth and metastasis, especially in lymph node metastasis (13,14). In our study, we demonstrated a significant relationship between CD44v6 expression and lymph node metastasis, lymphatic invasion, depth of invasion and stage by univariate analyses.…”

Section: Discussionsupporting

confidence: 57%

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CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Okayama

Kumamoto²,

Saitou³

et al. 2009

Oncol Rep

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Abstract. The aim of this study was to examine the expression of CD44v6, CD54, Cdx2, CXCL5, Cyclin B1, MMP-7, nm23, RCAS1 and Survivin in primary gastric cancer and to investigate whether these molecules were useful in predicting the lymph node status. They were selected as candidates for indicators of lymph node metastasis from various kinds of cancer-associated genes reported previously. In 135 cases of radically resected primary gastric adenocarcinoma, we investigated the association between the expression of these molecules and clinocopathologic factors by immunohistochemistry. The results revealed that the expression of CD44v6 and MMP-7 were significantly associated with lymph node status. By contrast, nuclear Cdx2 expression was found to be inversely correlated with lymph node metastasis. Moreover, multivariate analysis demonstrated that CD44v6, MMP-7 and nuclear Cdx2 were independent predictors for lymph node status. In conclusion, our results suggest that positive expression of both CD44v6 and MMP-7, and negative expression of nuclear Cdx2 may serve as powerful predictors of lymph node metastasis in gastric cancer. Combined evaluation of these markers could be further useful to predict lymph node status clinically.

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Section: Discussionsupporting

confidence: 57%

“…It has been reported that CD44v6 is correlated with regulating tumor invasion, progression and metastasis in various kinds of malignancies including gastric cancer (11,12). In addition, CD44v6 was significantly correlated with lymph node metastasis in gastric cancer (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Okayama

Kumamoto²,

Saitou³

et al. 2009

Oncol Rep

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show abstract

“…into the Cox regression model, which may have helped improve prediction of the median survival duration in patients after resection of primary gastric carcinoma. Previous studies showed that expression of biological markers such as p53 (38), nm23 (39), CD44 (40), and ErbB2 (41) is predictive of survival. Other studies, however, failed to show a correlation between many of these markers and overall prognosis (8,37).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Phosphorylated Mammalian Target of Rapamycin Predicts Lymph Node Metastasis and Prognosis of Chinese Patients with Gastric Cancer

Wang

Chen

et al. 2009

Clinical Cancer Research

136

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Purpose: We determined the expression of mammalian target of rapamycin (mTOR) and its activated form, p-mTOR, in Chinese patients with gastric cancer and its clinical effects and underlying mechanisms. Experimental Design: Tissue microarray blocks containing gastric cancer tissue and matched noncancer gastric tissue specimens obtained from 1,072 patients were constructed. Expression of total mTOR and p-mTOR in these specimens was analyzed using immunohistochemical studies and confirmed by Western blotting. Results: The overall rates of total mTOR and p-mTOR overexpression were 50.8% (545 of 1,072) and 46.5% (499 of 1,072), respectively. The p-mTOR overexpression was significantly correlated with total mTOR overexpression. Overexpression of total mTOR protein was significantly correlated with tumor differentiation, T1/T2 tumors, and stage I/II/III disease, whereas p-mTOR overexpression was significantly correlated with lymph node metastasis and all stage disease. The Cox proportional hazards model revealed that the overexpression of p-mTOR, but not total mTOR, was an independent prognostic factor for gastric cancer. The overexpression of p-mTOR also predicted the angiogenic phenotype of human gastric cancer and regulated angiogenesis of gastric cancer cells. Conclusions: Increased activation of mTOR is frequent in human gastric cancer and overexpression of p-mTOR is an independent prognostic factor, suggesting that mTOR pathway could be a potential target for therapy of this malignancy.

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“…Ishigami et al [25]insisted that patients with both slight invasion into the submucosa and less than 5 mm of horizontal expansion were often negative for lymph node involvement and thus might benefit from local surgery as an alternative to gastrectomy. Kurozumi et al [26]reported that expression of CD44-v6 and lymphatic invasion in gastric cancer tissues were independent risk factors for metastatic lymph nodes at diagnosis. We had already reported the significantly higher levels of serum soluble IL-2R in gastric cancer patients with lymph node metastasis compared to those without lymph node metastasis [4].…”

Section: Discussionmentioning

confidence: 99%

Serum Soluble Interleukin-2 Receptor as a Predictor of Lymph Node Metastasis in Early Gastric Cancer

Murakami

Sakata²,

Tsuji³

et al. 2002

Dig Surg

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Background: In the present study, we investigated the clinical significance of serum soluble IL-2R as a predictor of lymph node metastasis in patients with early gastric cancer. Patients and Methods: Seventy-four patients with early gastric cancer were enrolled in this study. Levels of serum soluble IL-2R were measured by an enzyme-linked immunosorbent assay. Result: Significant differences in serum soluble IL-2R between the control group and cases of T1 were not recognized. On the other hand, levels of serum soluble IL-2R in 74 patients with early gastric cancer (T1) were significantly lower than those of T2, T3, and T4 (p < 0.05). There were no significant differences in serum soluble IL-2R between cases of mucosal and submucosal invasion (379 ± 42 vs. 382 ± 35 U/ml). Six of 35 patients with submucosal invasion (17.1%) had lymph node metastasis, but none of the 39 patients with mucosal invasion. In the 6 cases showing lymph node metastasis, the macroscopic types were IIc + Ul(+) in 4, and IIc + IIa and IIc + IIb in 1, respectively. Histopathologically, there were 5 poorly and 1 moderately differentiated adenocarcinomas. In 6 cases with lymph node metastasis, serum soluble IL-2R levels were significantly higher than in those without lymph node metastasis (556.8 ± 73 vs. 329 ± 22 U/ml, respectively, mean ± SEM, p < 0.05). Five of these 6 cases demonstrated statistically significantly increased levels of serum soluble IL-2R (sensitivity 83%, specificity 63%), suggesting serum soluble IL-2R as a predictor of lymph node metastasis in early gastric cancer (p < 0.05). Conclusion: According to these data, in patients of early gastric cancer with increased levels of serum soluble IL-2R, endoscopic mucosal resection or minimal invasive gastrectomy without dissection of regional lymph nodes should be avoided, since there is a high risk of lymph node metastasis.

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Expression of CD44 Variant 6 and Lymphatic Invasion: Importance to Lymph Node Metastasis in Gastric Cancer

Cited by 29 publications

References 18 publications

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Overexpression of Phosphorylated Mammalian Target of Rapamycin Predicts Lymph Node Metastasis and Prognosis of Chinese Patients with Gastric Cancer

Serum Soluble Interleukin-2 Receptor as a Predictor of Lymph Node Metastasis in Early Gastric Cancer

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