Abstract 140: Clonal evaluation of ERG/SPINK1 status to determine disease progression using whole mount prostatectomy specimens

Abstract

Abstract Most primary prostate cancers are multifocal, marked by distinct tumor foci. Multiclonality is not routinely incorporated at clinical evaluation, however, marker status as a pathological parameter holds great potential for improving prognostic accuracy. Here, we evaluated the frequency of multiclonality and whether ERG/SPINK1 status is correlated to aggressive disease in whole-mount specimens. For each of the 89 radical prostatectomy cases, one H&E-stained whole-mount slide and a corresponding dual ERG/SPINK1 IHC stained slide were collected. Aperio AT2 scanner (Leica Biosystems) digitized these slides into whole-slide images (WSIs). All WSIs were reviewed by a pathologist with the aid of an automatic Gleason grading software to identify each tumor focus and determine its Gleason grade group (GG), and the expression levels (% uptake) of ERG and SPINK1, respectively. Grade groups 4 and 5 were treated as one high-grade group (GG4-5). The associations among GG, ERG, and SPINK1 expression levels were analyzed. For each WSI, 1 to 7 (median 2, mean 2.53) tumor foci were identified, and the aforementioned values were determined, resulting in 225 data records. The number of tumor foci, ERG/SPINK1 expression statistics, and their association for each GG are shown in the table. ERG was expressed the most frequently in GG1, and its frequency decreased as the grade increased. Conversely, SPINK1 expression frequency increased with the grade group. The expression of ERG and SPINK1 was inversely correlated regardless of grade group. More detailed results on the exploratory data analysis and the association with BCR will be shared at the time of presentation. ERG or SPINK1 expression do not appear to be associated with Gleason grade groups. More studies are needed to see if these markers may predict recurrence free survival or patient response to therapy. To our knowledge, this is the first study to map molecular subtypes in whole-mount samples utilizing a foci-based approach. Table Grade group Total ERG SPINK1 ERG-SPINK1 positive ratio (%) positive ratio (%) co-positive co-negative mutually exclusive GG1 74 38 51.4 24 32.4 4 16 54 GG2 81 35 43.2 40 49.4 7 13 61 GG3 33 11 33.3 22 66.7 4 4 25 GG4-5 37 10 27.0 13 35.1 1 15 21 Overall 225 94 41.8 99 44.0 16 48 161 Citation Format: Joonyoung Cho, In Hye Suh, HyeYoon Chang, Tae-Yeong Kwak, Sun Woo Kim, Nallasivam Palanisamy. Clonal evaluation of ERG/SPINK1 status to determine disease progression using whole mount prostatectomy specimens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 140.