Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico; Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico.
Instituto de Enfermedades de la Mama, FUCAM, Ciudad de México, Mexico.
Ann Diagn Pathol. 2022 Oct;60:151705. doi: 10.1016/j.anndiagpath.2021.151705. Epub 2021 Jan 12.
The aim of this study was to investigate the expression of leptin (LEP) and its receptor (LEPR) in breast cancer tissue of postmenopausal women with different body mass indexes (BMI), as well as the relationship of this expression with the rate of recurrence free survival (RFS). Leptin and LEPR expression, determined by immunohistochemistry, were studied in breast cancer tissues of 154 patients. Qualitative and semi-quantitative analysis of protein expression was performed by the H-Score method, through the ImageJ's IHC Profiler software. Kaplan-Meier survival analysis and log-rank statistic were used to estimate RFS differences. Protein expression of LEP, was significantly higher in women with overweight or with obesity, when compared to women with normal BMI (P = 0.032 and P = 0.013, respectively). We also observed a significantly higher expression of LEPR in breast tumor cells of women with obesity (58.8%), when compared to women with normal BMI (32.7%) (P = 0.007). Five-year survival rate, regarding LEPR expression, was 82.4% when positive and 94% when negative (P = 0.024). In the Cox proportional-hazards regression model, LEPR expression represented a risk factor for disease recurrence after adjustment for confounding factors (HR = 4.67; 95% CI: 1.13-19.31; P = 0.033). In conclusion, postmenopausal women with obesity and breast cancer present higher LEP and LEPR expression in breast tumors, when compared to women with normal BMI. Independently from BMI, women with tumors LEPR positive have worst RFS, when compared to women with tumors LEPR negative.
本研究旨在探讨瘦素(LEP)及其受体(LEPR)在不同体质量指数(BMI)的绝经后女性乳腺癌组织中的表达,以及这种表达与无复发生存率(RFS)的关系。通过免疫组织化学检测了 154 例患者乳腺癌组织中瘦素和 LEPR 的表达。采用 ImageJ 的 IHC Profiler 软件,通过 H-Score 法对蛋白表达进行定性和半定量分析。采用 Kaplan-Meier 生存分析和对数秩检验估计 RFS 差异。LEP 蛋白表达在超重或肥胖女性中明显高于正常 BMI 女性(P=0.032 和 P=0.013)。我们还观察到肥胖女性(58.8%)乳腺癌肿瘤细胞中 LEPR 的表达明显高于正常 BMI 女性(32.7%)(P=0.007)。LEPR 表达的 5 年生存率为阳性时为 82.4%,阴性时为 94%(P=0.024)。在 Cox 比例风险回归模型中,LEPR 表达在调整混杂因素后代表疾病复发的危险因素(HR=4.67;95%CI:1.13-19.31;P=0.033)。总之,与 BMI 正常的女性相比,肥胖的绝经后女性乳腺癌组织中 LEP 和 LEPR 的表达更高。独立于 BMI,LEPR 阳性肿瘤的女性 RFS 最差,而 LEPR 阴性肿瘤的女性 RFS 最好。