Carlos Gustavo Hirth1, Gislane Rocha Vasconcelos2, Marcos Venício Alves Lima3, Maria do Perpétuo Socorro Saldanha da Cunha4, Ingrid Kellen Sousa Frederico2, Conceição Aparecida Dornelas5. 1. Department of Pathology and Forensic Medicine, Postgraduate Program in Medical-Surgical Sciences of the Department of Surgery of the Federal University of Ceará, Hospital Haroldo Juaçaba, Ceará Cancer Institute, Brazil. Electronic address: carlos.hirth@ufc.br. 2. Hospital Haroldo Juaçaba, Ceará Cancer Institute, Pathology Laboratory, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil. 3. Hospital Haroldo Juaçaba, Ceará Cancer Institute, Rodolfo Teófilo College, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil. 4. Hospital Haroldo Juaçaba, Ceará Cancer Institute, Urology Clinical, Rodolfo Teófilo College, Albert Sabin Hospital, 1222, Papi Junior St. Rodolfo Teófilo, Fortaleza, Ceará 60351-010, Brazil. 5. Department of Pathology and Forensic Medicine and Department of Surgery, Postgraduate Program in Medical-Surgical Sciences of the Department of Surgery of the Federal University of Ceará, Departamento de Patologia e Medicina Legal, Universidade Federal do Ceará, Rua Monsenhor Furtado, s/n, Rodolfo Teófilo, Fortaleza, Ceará 60441-750, Brazil.
Abstract
BACKGROUND: Risk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. PATIENTS AND METHODS: Non-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. RESULTS: Our cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203-2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878-1.499]; p = 0.313). CONCLUSION: Non-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.
BACKGROUND: Risk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. PATIENTS AND METHODS: Non-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. RESULTS: Our cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203-2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878-1.499]; p = 0.313). CONCLUSION: Non-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.