Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma - PubMed (original) (raw)

Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma

Sang G Jung et al. Cancer Sci. 2010 Sep.

Abstract

The Notch signaling pathway is an important cell signaling system, which regulates cell differentiation, proliferation, and apoptosis, and is aberrantly activated in a wide range of cancer, including ovarian cancers. However, it remains unclear as to whether Notch signaling plays a role in the progression and prognosis of ovarian cancer. We examined the mRNA and protein expression of Notch 3, Jagged 1, and Jagged 2 in 98 ovarian epithelial tumors via real-time PCR and in 175 tumors with immunohistochemical analysis, and then correlated their expression levels with clinicopathological parameters and patient survival. In this study, we detected high levels of Notch3 mRNA and protein expression especially in serous ovarian carcinomas compared to their benign counterparts, accompanied by a positive correlation with the expressions of Jagged 1 and Jagged 2. High levels of Notch 3 mRNA expression (>2-fold than that of benign tumor) were noted in 63% of the serous carcinomas (mean level: 17-fold, P = 0.032). Additionally, Notch 3 protein overexpression was significantly associated with advanced stage (P = 0.0008), lymph node (P = 0.001), and distant metastasis (P = 0.003). Notably, high Notch 3 mRNA and protein expressions were correlated with chemoresistance (P = 0.033) and poor overall survival (P = 0.027, P = 0.042) in these patients. Our results indicate that the Notch 3 signaling pathway is involved in the tumor progression of ovarian serous carcinoma, and higher Notch 3 expression may be an independent poor prognostic factor in this subset of tumors.

© 2010 Japanese Cancer Association.

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Figures

Figure 1

Figure 1

Comparison of Notch 3, Jagged 1, and Jagged 2 mRNA expressions via quantitative real‐time PCR. (a) Serous tumor. Notch 3 mRNA expression was significantly increased (17‐fold, P = 0.032) in serous carcinomas as compared to benign serous tumors. (b) Mucinous tumor. The expression of Notch 3 and Jagged 1 in mucinous adenocarcinomas tended to decrease by 0.5‐fold as compared to its benign counterparts.

Figure 2

Figure 2

Correlation of Notch 3, Jagged 1, and Jagged 2 mRNA expression. Notch 3 mRNA expression was correlated positively with Jagged 1 and Jagged 2 mRNA expression (Pearson’s correlation, P = 0.01, 0.01).

Figure 3

Figure 3

Immunohistochemical stain of representative cases. The number of right lower corner is the immunohistochemical score. (a) The expression of Notch 3 was significantly higher in malignant serous tumors compared to benign serous tumors. The nuclear staining of carcinoma cells is noted. (b) The expression of Jagged 1 was not significantly different between benign, borderline, and malignant tumors in serous and mucinous tumors. (c) The expression of Jagged 2 was significantly higher in malignant tumors of serous and mucinous types compared to benign tumors.

Figure 4

Figure 4

Correlation of Notch 3 immunoreactive scores with clinicopathological parameters. Notch 3 overexpression was associated significantly with advanced International Federation of Gynecology and Obstetrics (FIGO) stage (a, P = 0.0008), lymph node metastasis (b, P = 0.001), and distant metastasis (c, P = 0.003) in serous carcinoma.

Figure 5

Figure 5

Kaplan–Meier overall survival curve. The higher expression group of Notch 3 mRNA (>2‐fold than benign tumor) demonstrated a significantly worse overall survival (P = 0.027) in ovarian serous carcinomas.

References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009; 59(4): 225–49. - PubMed
    1. Armstrong DK, Bundy B, Wenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354(1): 34–43. - PubMed
    1. Simpson P. Notch signalling in development: on equivalence groups and asymmetric developmental potential. Curr Opin Genet Dev 1997; 7(4): 537–42. - PubMed
    1. Yan XQ, Sarmiento U, Sun Y et al. A novel Notch ligand, Dll4, induces T‐cell leukemia/lymphoma when overexpressed in mice by retroviral‐mediated gene transfer. Blood 2001; 98(13): 3793–9. - PubMed
    1. Gallahan D, Callahan R. The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4). Oncogene 1997; 14(16): 1883–90. - PubMed

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