Widodo Irianiwati, Dwianingsih Ery Kus, Utoro Totok, Anwar Sumadi Lukman, Aryandono Teguh, Soeripto Soeripto
Asian Pac J Cancer Prev. 2018 Sep 26;19(9):2461-2467. doi: 10.22034/APJCP.2018.19.9.2461.
Background: Breast carcinomas (BCs) are sub-classified according to the molecular characteristics into luminal and non-luminal subtypes that clinically show different biological behavior, treatment and prognosis. BCs spread primarily through lymphatic vessels using cascade processes of lymphagiogenesis in which VEGF-C plays an important role during lymph node metastasis. Prognostic value of VEGF-C in luminal and non-luminal BC is still unclear and has not been studied thoroughly to clarify and define prognosis and therapeutic monitoring. Aim: To define the prognostic value of lymphangiogenesis on survival rates of luminal and non-luminal subtypes BC. Materials and Methods: This study applied prospective cohort design, using 130 patients of invasive duct carcinoma of the breast, stage I-IIIA, from Sardjito General Hospital, Indonesia and subsequent longitudinal follow-up. Immunohistochemical staining was carried out using anti-ER, -PR, -Her-2, VEGF-C, VEGFR-3 and D2-40 antibodies. The related clinicopathologic characteristics of BC patients and lymphangiogenesis determinants, including VEGF-C expression, were statistically analyzed. Results: In non-luminal BC subtypes, VEGF-C expression (HR=0.04; 95% CI=0.01-0.41), lymph node metastasis (HR=0.14; 95% CI=0.04-0.55) and stage (HR=0.30; 95% CI= 0.02-0.76) were determined as independent prognostic factors on survival rates. However, the lymphangiogenesis determinants were not associated with the survival rates of luminal BC subtypes. Conclusion: This study suggested that lymphangiogenesis affects survival rates of non-Luminal subtype rather than the luminal subtypes of BC.
乳腺癌(BC)根据分子特征分为管腔型和非管腔型亚型,临床上表现出不同的生物学行为、治疗方法和预后。乳腺癌主要通过淋巴管生成的级联过程经淋巴管扩散,其中血管内皮生长因子C(VEGF-C)在淋巴结转移过程中起重要作用。VEGF-C在管腔型和非管腔型乳腺癌中的预后价值仍不清楚,尚未进行充分研究以阐明和界定预后及治疗监测。目的:确定淋巴管生成对管腔型和非管腔型乳腺癌亚型生存率的预后价值。材料与方法:本研究采用前瞻性队列设计,纳入印度尼西亚萨吉托综合医院130例I-IIIA期乳腺浸润性导管癌患者,并进行后续纵向随访。使用抗雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her-2)、VEGF-C、血管内皮生长因子受体3(VEGFR-3)和D2-40抗体进行免疫组织化学染色。对乳腺癌患者的相关临床病理特征和淋巴管生成决定因素,包括VEGF-C表达进行统计学分析。结果:在非管腔型乳腺癌亚型中,VEGF-C表达(风险比[HR]=0.04;95%置信区间[CI]=0.01-0.41)、淋巴结转移(HR=0.14;95%CI=0.04-0.55)和分期(HR=0.30;95%CI=0.02-0.76)被确定为生存率的独立预后因素。然而,淋巴管生成决定因素与管腔型乳腺癌亚型的生存率无关。结论:本研究表明,淋巴管生成影响非管腔型乳腺癌亚型的生存率,而非管腔型乳腺癌亚型。