Introduction:Ovarian cancer is the fifth most common cause of cancer deaths among women with the majority of cases diagnosed at an advanced stage where therapeutic options are limited to surgical resection and adjuvant platinum-based chemotherapy regimens. Given the paucity of reliable tissue biomarkers to predict response to therapy, we used a validated quantitative multiplex immunofluorescent (QMIF)platform on formalin-fixed, paraffin-embedded (FFPE) ovarian tissues to quantify biomarker expression patterns and assessed association with outcome.
Methods: 89 patients were evaluated using tissue microarrays consisting of three 0.6mm tumor cores per diagnostic specimen; fallopian tubes and four different ovarian cell lines were included as pos/neg controls. CK7, VEGF, PERK1/2 and TP53 were evaluated with QMIF, with individual and combined antibody features constructed utilizing intensity and area values. Kaplan-Meier with log-rank test along with multivariate Cox proportional hazards model were employed to determine biomarker assocation with respect to overall (OS) and progression free survival (PFS).
Results: Mean age 59yrs, 80% serous, 88% Grade 3 and 85% >/= Stage IIIC. Median follow-up 32m; 5-year OS 51% and platinum resistance 54%. In multivariate analysis CK7+TP53+ was an independent prognostic marker for both PFS and OS (p-value <0.001 and 0.04), i.e greater amounts associated with decreased survival. By contrast, increased levels of PERK1/2 were associated with a decreased tumor recurrence and increased platinum sensitivity (p=0.020 and 0.006) while increasing amounts of VEGF were associated with greater tumor recurrence (p=0.004) as well as platinum sensitvity (p=0.03).Conclusion: Quantitative assessment of TP53, PERK1/2 and VEGF provides valuable (biological) information with respect to chemoresponse and tumor recurrence. The application of QMIF to biomarker investigation will provide another level of complexity to tumor phenotypic characterization which is currently not available using standard subjective, chromogenic IHC assays.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B182.
Citation Format: Joel Cardenas-Goicoechea, Nguyen Long, Tamara Kalir, Michael J. Donovan. Utilization of quantitative multiplex immunofluorescence to assess biomarkers in ovarian cancer; ability to create an objective phenotype with respect to outcome. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B182.