Annexin XI Is Associated with Cisplatin Resistance and Related to Tumor Recurrence in Ovarian Cancer Patients

¹ Departments of ¹Pathology and ²Gynecology/Obstetrics and Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland

^* To whom correspondence should be addressed. E-mail: zzhang7{at}jhmi.edu.

	Abstract

Purpose: Ovarian cancer patients treated with cisplatin-based chemotherapy often develop acquired cisplatin resistance and, consequently, cancer recurrence. The precise nature of chemoresistance remains unclear. In this study, a protein identified to be associated with cisplatin resistance in ovarian cancer cells was investigated in ovarian cancer tissues to address its clinical significance.

Experimental Design: Antibody microarrays were used to identify proteins consistently differentially expressed across three pairs of cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Immunoblotting was used to confirm observed alteration of protein expression. The protein expression was further evaluated by immunohistochemical staining using tissue microarrays containing various human normal and malignant tissues and 164 surgical specimens derived from primary and recurrent ovarian cancer patients who underwent primary debulking surgery followed by standard chemotherapeutic regimen.

Results: Annexin XI was down-regulated in all three cisplatin-resistant cell lines as compared with their parent cells. Annexin XI expression was observed in the majority of human normal organs and decreased in some of the most common human malignancies. The expression level of Annexin XI in first recurrent ovarian cancers was much lower than that in primary ovarian cancers (P = 0.0004). Increased Annexin XI immunoreactivity in ovarian cancers seemed to prolong the disease-free interval of patients (P = 0.03). Annexin XI immunoreactivity inversely correlated with in vitro cisplatin resistance in ovarian cancers (P = 0.01).

Conclusion: Decreased expression of Annexin XI is characteristic for cisplatin-resistant cancer cells and may contribute to tumor recurrence. Annexin XI may be a potential marker for chemoresistance and earlier recurrence of ovarian cancer patients.

Key Words: Ovarian cancer, Annexin XI, Cisplatin, Antibody Microarray, Immunohistochemistry