AZGP1 and SPDEF mRNA expression differentiates breast carcinoma from ovarian serous carcinoma

Helene Tuft Stavnes, Dag André Nymoen, Anita Langerød, Arild Holth, Anne-Lise Børresen Dale, Ben Davidson
Virchows Archiv: An International Journal of Pathology 2013, 462 (2): 163-73
The ANPEP, AZGP1, and SPDEF genes were previously found to be overexpressed in breast compared to ovarian carcinoma effusions. The present study validated this finding in a larger cohort consisting of both primary and metastatic tumors. ANPEP, AZGP1, and SPDEF mRNA expression was investigated in 83 breast carcinomas (57 primary carcinomas and 26 effusions) and 40 ovarian carcinomas (20 primary carcinomas and 20 effusions) using qPCR. ANPEP protein expression was immunohistochemically analyzed in 53 breast carcinoma effusions and patient-matched primary carcinomas (n = 25) and lymph node metastases (n = 16). mRNA and protein levels were studied for association with tumor type and anatomic site, and for clinical role in breast carcinoma. AZGP1 and SPDEF mRNA was overexpressed in breast compared to ovarian carcinoma (both p < 0.001). AZGP1 mRNA was overexpressed in primary breast carcinoma compared to effusions (p < 0.001), with opposite findings for ANPEP (p = 0.044). AZGP1 mRNA expression correlated with positive ER status (p = 0.032) and grade 1 histology (p = 0.011), whereas SPDEF mRNA levels were associated with positive ER (p = 0.002) and PR (p = 0.013) status and tamoxifen treatment (p = 0.004). ANPEP protein expression was higher in breast carcinoma effusions compared to primary tumors and lymph node metastases (both p = 0.001). ANPEP, AZGP1, and SPDEF levels were unrelated to disease-free or overall survival. This is the first study documenting ANPEP, AZGP1, and SPDEF expression in breast carcinoma effusions. AZGP1 and SPDEF may be novel molecular markers for the differentiation of breast from ovarian carcinoma. ANPEP may be involved in breast carcinoma progression in view of its overexpression in effusions compared to solid specimens.

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