Expression of androgen receptor splice variant, AR-V7, in high-grade serous ovarian cancer

Abstract

<h3>Objectives:</h3> Androgen receptors (AR) are expressed in up to 55% of ERα-negative breast cancers overall and up to 35% of those classified as TNBC. Similarly, AR is expressed in approximately 40% of high grade serous ovarian cancer (HGSOC). The development of AR splice variants (AR-SV), particularly AR-V7, has been shown to be a poor prognostic feature, and mechanism of androgen resistance in breast and prostate cancers. We sought to determine if AR-V7 was present in HGSOC and if there was a correlation with platinum sensitivity and/or treatment outcomes. <h3>Methods:</h3> Pair-matched chemo-naïve and platinum-treated HGSOC specimens were identified from our tissue repository. Formalin-fixed paraffin-embedded tumor (FFPE) blocks were collected and tested for expression of AR-V7. Gene fusion detection and variant detection were performed on mRNA isolated from a formalin-fixed paraffin-embedded tumor sample using the Illumina NovaSeq platform (Illumina, Inc., San Diego, CA) and Agilent SureSelect Human All Exon V7 bait panel (Agilent Technologies, Santa Clara, CA). FFPE specimens underwent pathology review to diagnose percent tumor content and tumor size; a minimum of 10% of tumor content in the area for microdissection was required. <h3>Results:</h3> Twelve chemo-naïve specimens collected at time of diagnosis by initial biopsy (n=8) or primary debulking surgery (n=4) were pair-matched with the patients' subsequent platinum-treated specimens from either interval debulking surgery (n=6) or biopsy of recurrence (n=6). Following penultimate platinum, 50% were platinum resistant and 50% were platinum sensitive at time of second pathology. Only 19 of the 24 specimens submitted had sufficient RNA for testing, 8 chemo-naïve and 11 platinum-treated. AR-V7 variant transcript was not detected in any of the specimens submitted. <h3>Conclusions:</h3> AR-V7 was not expressed in any specimen before or after platinum based chemotherapy suggesting it may not be a useful prognostic marker in the management of HGSOC. Further investigation into gynecologic malignancies with high AR expression and treated with androgen deprivation therapy may elucidate different results.