No abstract

259 Background: Histological subtypes of Pca are generally associated with worse clinical outcomes. Here in, we hypothesize that histological subtypes of PCa, e.g., cribriform, and signet ring-like, may have distinct genomic characteristics that may unravel new therapeutic targets. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: Pathology slides of advanced PCa (with cribriform and signet ring-like histology, and non-cribriform/signet ring-like histology as control) with transcriptomic data available. Only Gleason grade 4 or 5 were included to ensure homogeneity in population. Histology was independently reviewed by two genitourinary pathologists. RNA-sequencing of treatment naive primary prostate tissue was performed by a CLIA certified lab. DeSeq2 analysis was implemented in Bioconductor Software to analyze differentially expressed genes in patients with cribriform versus non-cribriform and signet ring-like versus non-signet ring-like histology. DeSeq2 results included the Log2 Fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values for each differentially expressed gene. These results were then subjected to Gene Set Enrichment Analysis (GSEA) in order to identify pathways upregulated or downregulated in each cohort. All bioinformatic analysis was conducted in R-Studio, version 4.1.1. Statistical significance level was predetermined at 0.05. Results: 34 patients were included: cribriform histology n=17, signet ring-like n=4, control non-cribriform/signet ring-like PCa n=13 (control were matched for age, PSA and disease volume). Compared to control, upregulated pathways in cribriform histology included adipogenesis, fatty acid and xenobiotic metabolism, while the down regulated pathways included mitotic spindle, G2M checkpoint and E2F targets. In signet ring-like histology, inflammatory response pathways were upregulated; DNA repair, MYC targets and androgen response pathways were downregulated. Conclusions: Cribriform, and signet ring-like histologic subtypes were noted to have distinct genomic expression profile. These data may need further validation and will guide further drug development.

Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.