Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.
Department of Veterinary Surgery, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
PLoS One. 2024 Jul 16;19(7):e0306398. doi: 10.1371/journal.pone.0306398. eCollection 2024.
Myeloid cell leukemia-1 (MCL-1), which belongs to the anti-apoptotic B cell lymphoma-2 family protein, is overexpressed in various cancers and is associated with cell immortality, malignant transformation, chemoresistance, and poor prognosis in humans. However, the significance of MCL-1 in canine mammary gland tumors (MGTs) remains unknown. This study aimed to examine MCL-1 expression in normal canine mammary glands and tumors and to assess its correlation with clinical and histologic variables. In total, 111 samples were examined, including 12 normal mammary gland tissues, 51 benign MGTs, and 48 malignant MGTs. Immunohistochemistry revealed that 53% of benign tumors and 75% of malignant tumors exhibited high MCL-1 expression, whereas only 8% of normal mammary glands exhibited high MCL-1 expression. High MCL-1 expression correlated with tumor malignancy (p < 0.001), large tumor size (> 3 cm) (p = 0.005), high Ki-67 expression (p = 0.046), and metastasis (p = 0.027). Survival curve analysis of dogs with malignant MGTs demonstrated a significant association between high MCL-1 expression and shorter median overall survival (p = 0.027) and progression-free survival (p = 0.014). Our study identified MCL-1 as a prognostic factor and potential therapeutic target in canine MGTs.
髓样细胞白血病-1（MCL-1）属于抗凋亡 B 细胞淋巴瘤-2 家族蛋白，在各种癌症中过度表达，与人类细胞的永生、恶性转化、化疗耐药和预后不良有关。然而，MCL-1 在犬乳腺肿瘤（MGT）中的意义尚不清楚。本研究旨在检测正常犬乳腺组织和肿瘤中的 MCL-1 表达，并评估其与临床和组织学变量的相关性。共检查了 111 个样本，包括 12 个正常乳腺组织、51 个良性 MGT 和 48 个恶性 MGT。免疫组织化学显示，53%的良性肿瘤和 75%的恶性肿瘤表现出高 MCL-1 表达，而只有 8%的正常乳腺组织表现出高 MCL-1 表达。高 MCL-1 表达与肿瘤恶性程度（p < 0.001）、肿瘤较大（>3cm）（p = 0.005）、Ki-67 高表达（p = 0.046）和转移（p = 0.027）相关。对患有恶性 MGT 的犬进行生存曲线分析表明，MCL-1 高表达与中位总生存时间（p = 0.027）和无进展生存时间（p = 0.014）较短显著相关。本研究鉴定了 MCL-1 作为犬 MGT 的预后因素和潜在的治疗靶点。
