Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Cancer Sci. 2012 Feb;103(2):382-9. doi: 10.1111/j.1349-7006.2011.02151.x. Epub 2011 Dec 15.
Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co-expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5-year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC.
三阴性乳腺癌(TNBC)是一种异质性、侵袭性癌症,目前尚无有效的化疗或靶向治疗方法。我们旨在评估 L 型氨基酸转运蛋白(LAT)1 和 CD98 在乳腺癌患者中的免疫组织化学表达,尤其是在 TNBC 患者中。在 129 例患者中,LAT1 阳性者 56 例(43.4%),CD98 阳性者 41 例(31.8%)。LAT1 表达阳性在 luminal A 病例中的阳性率为 7.9%,luminal B 病例为 30.0%,HER2 病例为 71.4%,TN 病例为 64.0%。HER2 和 TN 亚型的 LAT1 和 CD98 表达水平高于 luminal A 和 B 亚型(均 P < 0.001)。LAT1 和 CD98 的表达与肿瘤大小(LAT1,P = 0.010;CD98,P = 0.007)、核分级(LAT1,P < 0.001;CD98,P < 0.001)和 Ki67 标记指数(LAT1,P < 0.001;CD98,P = 0.001)相关。LAT1 和 CD98 的表达与 ER 和 PgR 呈负相关(均 P < 0.001)。在 TNBC 中,CD98+(63.6%)或 LAT1+/CD98+(61.9%)患者的 5 年无病生存率明显低于 CD98-(89.3%)患者或无 LAT1 和 CD98 共表达(89.7%)的患者(P = 0.014,P = 0.009)。CD98 阳性/阴性患者的 5 年生存率分别为 77.3%和 100%(P = 0.050),而 LAT1+/CD98+患者的生存率(76.2%)明显较差(100%)(P = 0.040)。多因素分析证实,CD98+或 LAT1+/CD98+表达是 TNBC 复发的危险因素(P = 0.023,P = 0.019)。因此,在本研究中我们表明,LAT1 和 CD98 的表达是预后因素。抑制这些蛋白可能为 TNBC 提供一种新的治疗策略。
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