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, Fortaleza, Ceará, Brazil.
Haroldo Juaçaba Hospital, Ceará Cancer Institute, Brazil.
Ann Diagn Pathol. 2022 Feb;56:151843. doi: 10.1016/j.anndiagpath.2021.151843. Epub 2021 Oct 20.
CUL2 plays a crucial role in proteolysis by preserving the balance between normal growth and uncontrolled proliferation. HSPA9 safeguards the integrity of protein interactions and supports cellular homeostasis. In carcinomas, HSPA9 and CUL2 appear to protect neoplastic cells from internal and external damage. In prostate tumors they are apparently associated with increased risk of unfavorable outcomes, but information remains scarce. In this study we evaluated CUL2 and HSPA9 expression in neoplastic and non-neoplastic prostate tissue and Gleason pattern 3 and 4 adenocarcinoma to identify associations with ISUP prognostic groups and postoperative disease progression. The records of 636 radical prostatectomy patients were reviewed retrospectively and microarrays were mounted with paraffin-embedded adenocarcinoma and non-neoplastic tissue. We evaluated the ability of HSPA9 and CUL2 to predict postoperative PSA outcomes, response to adjuvant/salvage therapy and systemic disease. HSPA9 and CUL2 were diffusely expressed. HSPA9 expression was associated with increased risk of high-grade adenocarcinoma, while HSPA9 and CUL2 were associated with biochemical failure after salvage therapy. In conclusion, HSPA9 and CUL2 were highly expressed in prostate tissue, especially in neoplastic cells. HSPA9 and CUL2-positive Gleason pattern 3 adenocarcinoma was more likely to be associated with Gleason pattern 4 or 5, while HSPA9 and CUL2-positive Gleason pattern 4 adenocarcinoma was less likely to belong to ISUP groups 1 and 2. Staining for HSPA9 and CUL2 can help identify patients at increased risk of recurrence after salvage therapy.
CUL2 通过维持正常生长和不受控制的增殖之间的平衡在蛋白水解中发挥关键作用。HSPA9 保护蛋白相互作用的完整性并支持细胞内稳态。在癌中，HSPA9 和 CUL2 似乎保护肿瘤细胞免受内部和外部损伤。在前列腺肿瘤中，它们显然与不良结局风险增加相关，但信息仍然有限。在这项研究中，我们评估了 CUL2 和 HSPA9 在肿瘤和非肿瘤前列腺组织以及 Gleason 3 和 4 腺癌中的表达，以确定与 ISUP 预后分组和术后疾病进展的关联。回顾性地审查了 636 例根治性前列腺切除术患者的记录，并使用石蜡包埋的腺癌和非肿瘤组织制作了微阵列。我们评估了 HSPA9 和 CUL2 预测术后 PSA 结果、对辅助/挽救治疗和全身疾病的反应的能力。HSPA9 和 CUL2 呈弥漫性表达。HSPA9 表达与高级别腺癌的风险增加相关，而 HSPA9 和 CUL2 与挽救治疗后的生化失败相关。总之，HSPA9 和 CUL2 在前列腺组织中高度表达，特别是在肿瘤细胞中。HSPA9 和 CUL2 阳性的 Gleason 3 腺癌更有可能与 Gleason 4 或 5 相关，而 HSPA9 和 CUL2 阳性的 Gleason 4 腺癌不太可能属于 ISUP 1 组和 2 组。HSPA9 和 CUL2 的染色有助于识别挽救治疗后复发风险增加的患者。
