Maspin overexpression correlates with positive response to primary chemotherapy in ovarian cancer patients

https://doi.org/10.1016/j.ygyno.2008.12.038Get rights and content

Abstract

Objective

Maspin is a member of the serine protease inhibitor superfamily. Experimental studies revealed that maspin suppresses tumor growth, angiogenesis, invasion and metastasis. We examined maspin expression in human ovarian tumors and relation between maspin expression and clinicopathological features as well as the role of maspin in predicting clinical outcome in patients with ovarian cancer.

Methods

Tissue samples consisted of 42 benign tumors, 10 borderline (LMP) tumors, 76 ovarian carcinomas, 8 Krukenberg tumors and 32 normal tissues. Immunoblot analysis was performed to evaluate the relative expression of maspin/β-actin.

Results

Relative maspin level was significantly higher in patients with LMP tumors (median 0.74) and early stages ovarian cancers (median 0.46) when compared with healthy tissues (median 0.03), those with benign (median 0.23) and metastatic tumors (median 0.22). Overexpression of maspin was found to correlate with the early stage of the disease (p = 0.001), non-serous subtype of ovarian cancer (p = 0.03) and positive response to chemotherapy (p = 0.02). A statistically significant longer PFS was seen in women with high as compared with low expression of maspin (p = 0.03).

Conclusions

Maspin is upregulated in borderline tumors and the early stages of ovarian carcinoma and then significantly downregulated with malignant transformation. High expression may paradoxically promote the invasion and metastasis of ovarian carcinomas. Our study revealed that maspin expression could play an important role in predicting the results of treatment of ovarian cancer patients.

Section snippets

Patients and tissue samples

168 ovarian specimens were obtained during surgeries from patients who were treated in the Gynecology Oncology Department, Medical University of Gdańsk (from 04.2004 to 07.2007). The collection of tissues was supervised by a pathologist. Tissue samples were immediately frozen in liquid nitrogen and maintained at − 70 °C. Specimens consisted of 32 normal tissues (obtained from patients who underwent surgery for other gynecologic diseases than ovarian tumors), 42 benign tumors, 10 borderline (LMP)

Western blot analysis of maspin expression in ovarian tissue

Maspin was expressed as a protein band with a mass of 42 kDa. Interestingly, a second band of approximately 35 kDa was also reactive with the maspin antibodies in most tested samples. (The band of 60 kDa was a result of unspecific reaction with secondary antibodies) (Fig. 1). Maspin (42 kDa isoform) was expressed at detectable levels in 17/32 healthy tissue samples (53.1%) with relative expression ranging from 0.03 to 0.7, in 33/42 benign tumors (78.6%, 0.02–2.3), 9/10 borderline tumors (90%,

Discussion

The clinical importance of maspin in human cancers has been investigated since its discovery in 1994 [7]. Experimental studies revealed that maspin suppresses tumor growth, angiogenesis, invasion and metastasis [18], [19], [20], [23], [24]. Maspin is also involved in the process of cell apoptosis [21], [22]. The exact function of maspin as a tumor suppressor is not known, moreover its localization in different cell compartments (cytosol, nucleus, extracellular matrix), suggests that it may be

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

This work was supported by the Polish Ministry of Science and Higher Education (Grant No. N 40306631/3077).

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    Presented in part at the International Congress “Ovarian Cancer” Krakow, June 18–21, 2008.

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