Abstract
The Cancer Genome Atlas (TCGA) Research Network defined the SPOP-mutant subset of prostate cancers (PCa) had frequent overexpression of SPINK1 mRNA, which suggests a relationship in these subtypes that had not been evaluated simultaneously in other studies on ETS(-) subtypes as a key feature in the molecular taxonomy of prostate cancer. However, this analysis was performed on the index tumors and it is suggested that a better knowledge of the different molecular profiles of different neoplastic foci, in the same prostate, could be affecting the relationship of the molecular subtypes and prognosis of the disease. With an approximate 50% prevalence of ETS family gene fusions, attempts to molecularly characterize PCa often begin with the division into ETS(-) and ETS (+). To represent the molecular heterogeneity of PCa, which could improve medical decision-making, we aim to study it through the expression of SPINK-1 and mutations in SPOP; as well as the TMPRSS2-ERG fusion status, in order to assess the clonality of the foci in each patient and also the possible association of this alteration with different degrees of differentiation and lymph node metastasis. FFPE samples of different foci with different lesion degrees: High-Grade Prostatic Intraepithelial Neoplasia (n=17), PCa foci with different Gleason scores (n= 53; GL3: (n=23); GL4: (n=23) and GL5: (n=7)), and positive lymph node (LN) (n=13) from radical prostatectomy from twenty patients were used to analyse the presence of TMPRSS2-ERG fusion and expression levels of ERG and SPINK-1 using RT-PCR. Sanger sequencing was used in exon 6 and 7 to analyze mutations in SPOP. The molecular concordance between the different prostatic foci of the same patient was determined, taking into account subclonal events. The LN were compared with prostatic foci to try to establish its clonal origin. The results indicate that multifocal PCa may have monoclonal or multiclonal origin. SPINK-1 overexpression was the predominant pattern in the LN, while the opposite was the most frequent in the HGPIN samples. None of the thirteen analyzed LN showed the same pattern of other PCa foci from each patient. Metastasis have less molecular heterogeneity than pre-neoplastic lesions. The ERG(+) subtype was found in 54.7% of the foci and 70% of the patients. No mutations were found in SPOP. The frequency of overexpressed SPINK-1 in the 20 patients was 60%. In this study, the frequency of SPINK-1 cases overexpressed in ERG(-) taking into account all the samples analyzed as independent, even if they were from the same patient, due to the high heterogeneity in PCa, coincides with that expected (11%), but it should be taken into account that the foci that tested positive did not show total exclusivity with ERG(+), and in fact, there were more associated with it (74%), which does not agree with what was found in other studies that had not taken into account samples of patients from our country, which highlights the importance of personalized medicine and of not extrapolating results from other populations in our population.
Citation Format: Yenifer Y. Segura Moreno, María C. Sanabria Salas, Jorge A. Mesa López De Mesa, Rodolfo Varela Ramirez, Natalia L. Acosta Vega, Martha L. Serrano López. Multifocal analysis of the ETS (-) subtypes, mutated SPOP and overexpression of SPINK-1, in prostate cancer from Colombian patients as a process of understanding the carcinogenesis model of the disease [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-102.
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