Non-Ascites Forming High Grade Serous Carcinoma of Pelvis Is Associated with a Distinct Immune Signature and Characterised by T and B Cell Infiltration
Blaise A Clarke, Tomer Feigenberg, Carl Virtanen, Herman Chui, Michelle Letarte, Alexandra Kollara, Barry Rosen, Marcus Bernardini, Theodore J Brown, K Joan Murphy. University Health Network, University of Toronto, Toronto, ON, Canada; Ontario Cancer Institute, Toronto, ON, Canada; Sick Kids Hospital, Unversity of Toronto, Toronto, ON, Canada; Samuel Lunenfeld Research Institute, University of Toronto, Toronto, ON, Canada
Background: Studies have recently reported molecular subtypes of high grade serous carcinoma (HGSC) of the pelvis. Although these subgroups have been shown to have prognostic significance, histologic and clinical correlates of these subgroups are limited. We demonstrate on a limited number of cases that non-ascites forming HGSC of the pelvis is associated with the immune subgroup. In this study we further validate some of the differential biomarkers using tissue microarrays and correlate ascites status with intraepithelial B and T cell infiltration and tumor morphology.
Design: Whole genome gene expression profiling of primary tumor samples of 11 advanced stage high volume ascites HGSC and 9 advanced stage low volume ascites were compared. Significantly differentially expressed genes were mapped to the TCGA dataset. Validation of select differentially expressed biomarkers and assessment of T and B cell infiltration was performed on a tissue microarray containing 51 independent HGSC samples (25 high volume ascites and 26 low volume ascites). Blinded morphologic review of cases for pre-determined morphologic features [mitotic index, tumor infiltrating lymphocytes (TILS), necrosis, Silverberg grade] was performed.
Results: Of the fifty-two differentially expressed probes (p<0.05 with a 2-fold change cut-off), the low volume ascites group demonstrated enrichment of genes that regulate antigen presentation and T cell function, and this was shown to correspond to the immune subgroup. On TMA analysis, low volume ascites cases were significantly more likely to harbour intraepithelial T and B cells [CD3 (p= 0.009), CD8 (p= 0.0003) and CD20 (p=0.04)]. HLA-DA, CD 78 and TAP 2 were also significantly more highly expressed in this group. Our Initial results suggest that only TILS was shown to be significant on morphology review.
Conclusions: Low volume ascites HGSC of pelvis is characterised by enhanced immune response as demonstrated both with gene expression profiling, and with the presence of intraepithelial T and B cells and more intense expression of HLA-DA, CD78 and TAP2. Only TILS was found to be useful on morphology review. Additional morphologic studies using training and test set are being performed. Clinical correlates of immune response in HGSC are important as immunotherapy is considered.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 2:00 PM
Proffered Papers: Section B, Tuesday Afternoon