The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach

Ohtawa, Yasuyuki; Naomoto, Yoshio; Shirakawa, Yasuhiro; Takaoka, Munenori; Murata, Tadao; Sonoda, Ryotaro; Sakurama, Kazufumi; Yamatsuji, Tomoki; Gündüz, Mehmet; Tsujigiwa, Hidetsugu; Nagatsuka, Hitoshi; Terada, Norihiko; Itano, Satoshi; Horiki, Sadayuki; Yanagihara, Kazuyoshi; Nakajima, Motowo; Tanaka, Noriaki

doi:10.1016/j.humpath.2006.04.005

Cited by 10 publications

(16 citation statements)

References 20 publications

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“…However, no expression of Hpa protein or MAP was detected in normal gastric mucosal glands. These findings were consistent with previously published studies (15). According to the standard scoring used in immunohistochemical staining, the expression of the three different MAPs in gastric cancer tissues had clear discrepancies: i) a distinct higher expression of MAP2, and ii) no expression of MAP1 and MAP3, which was similar to the findings of our previous study which focused on hepatocellular carcinoma tissues (12).…”

Section: Discussionsupporting

confidence: 92%

Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy

et al. 2012

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Abstract. Tumor-associated antigens (TAAs) trigger a TAA-specific immune response, thus they are the crux of antitumor immunosurveillance. A major advance in tumor immunology in the last 20 years was marked by the verification that CTL or B-cell epitopes rather than integral TAAs induce immunoreactivity. Previous studies on the correlation between heparanase (Hpa) expression and clinical or pathological features have generally used commercial antibodies against full-length Hpa protein rather than the functional epitopes, and the antigen determinants of such antibodies have not yet been defined. In our investigation of Hpa peptide expression in gastric cancer tissues and its association with tumor invasion, metastasis and prognosis, we analyzed Hpa expression in the tissues of 132 patients with gastric cancer using tissue microarray (TMA) technology and immunohistochemical staining.Three self-developed rabbit polyclonal antibodies against Hpa multiple antigenic peptides (MAP) and one commercial polyclonal rabbit antibody against the 50-8 kDa Hpa heterodimer were used. Clinical and pathological significance was evaluated using the Chi-square test and Kaplan-Meier survival curve analysis. The results demonstrated that the positivity rates using the antibody against MAP2 and the commercial antibody were 60.6% (80/132) and 65.2% (86/132), respectively. No expression of either MAP1 or MAP3 was noted in the cancer tissues of the 132 cases. MAP2 behaved in a similar manner to the commercial antibody in that a higher Hpa expression was observed in the cancer tissues with vessel invasion, serosal involvement, distant metastasis, poor differentiation and TNM stages Ⅲ and Ⅳ. Moreover, the patients with a positive Hpa expression had a far poorer prognosis, with lower one-year and five-year survival rates. Our results demonstrate that in a similar manner to full-length Hpa proteins, MAP2 expression is closely associated with the invasion, metastasis and prognosis of gastric cancer. This finding may be of potential use in clinical therapy and in estimating the prognosis of a tumor.

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Section: Discussionsupporting

confidence: 92%

Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy

et al. 2012

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“…Elkin et al [22] have considered HPA-1 as a mediator in angiogenesis. Investigations on breast cancer [23], esophageal cancer [24], and gastric cancer [25] revealed that HPA promotes the expression of Cox-2 mRNA. In this study, we found HPA correlated with Cox-2 expression directly, which indicated that HPA-1 may promote angiogenesis by upregulating Cox-2 expression.…”

Section: Discussionmentioning

confidence: 99%

Heparanase-1 and Cyclooxygenase-2: prognostic indicators of malignancy in pheochromocytomas

Zhu

Yuan

et al. 2010

Endocr

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The objective of this article is to evaluate Heparanase-1 and Cyclooxygenase-2 as tissue-based markers of pheochromocytoma prognosis. Ninety-two sporadic pheochromocytoma patients with a minimum of 8-year follow-up post-diagnosis were enrolled. Slides of normal adrenal glands in nephrectomy specimens from 20 patients with benign renal tumors were as control. Heparanase-1 and Cyclooxygenase-2 expression as well as microvessel density were examined using immunohistochemistry in tissues from these patients. Positive staining for Heparanase-1 was observed in 23.68% of the benign and 77.78% of the malignant cases, whereas none of the normal adrenal controls showed positive staining. Similarly, Cyclooxygenase-2 staining was seen in 23.68% of the benign versus 83.33% of the malignant cases, and none of the normal controls appeared positive for Cyclooxygenase-2. Using both HPA-1 and Cox-2 combined, the positive predictive value of malignancy was significantly increased to 0.72, compared to about 0.45 by their own. Malignant cases showed higher microvessel density compared to benign tumors and normal controls (36.41, 21.43, and 13.36%, respectively). Heparanase-1 and Cyclooxygenase-2 may contribute to the invasive characteristics of malignant pheochromocytomas. Heparanase-1 and Cyclooxygenase-2 combined is better than their own to be used as a marker to distinguish malignant from benign pheochromocytoma.

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“…We have recently reported that HPSE and COX‐2 exhibit a similar expression pattern in oesophageal squamous cell carcinoma, and that exogenous transduction of HPSE could up‐regulate COX‐2 at a transcriptional level 16 . We further reported that there is a strong correlation of expression between HPSE and COX‐2 was observed in breast cancer 17 and in signet‐ring cell carcinoma of the stomach 18 . COX is a rate‐limiting enzyme in prostaglandin synthesis and has two isoforms; COX‐1 and COX‐2 19 .…”

Section: Introductionmentioning

confidence: 85%

“…In situ hybridization was done as described previously 18 . Briefly, the sections were deparaffinized, rehydrated and incubated with 3 mg/ml of proteinase K (Roche Diagnostics) in 10 m m Tris–HCl (pH 8.0) 0.5 m m ethylenediamine tetraaceticacid for 10 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Preferential up‐regulation of heparanase and cyclooxygenase‐2 in carcinogenesis of Barrett’s oesophagus and intestinal‐type gastric carcinoma

Sonoda¹,

Naomoto²,

Shirakawa³

et al. 2010

Histopathology

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The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach

Cited by 10 publications

References 20 publications

Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy

Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy

Heparanase-1 and Cyclooxygenase-2: prognostic indicators of malignancy in pheochromocytomas

Preferential up‐regulation of heparanase and cyclooxygenase‐2 in carcinogenesis of Barrett’s oesophagus and intestinal‐type gastric carcinoma

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