Ravaggi Antonella, Gambino Angela, Ferrari Federico, Olivari Alessandro, Zanotti Laura, Romani Chiara, Ardighieri Laura, Antonelli Paolo, Garganese Giorgia, Gallo Daniela, Scambia Giovanni, Bignotti Eliana, Sartori Enrico, Calza Stefano, Odicino Franco
Department of Clinical and Experimental Sciences, Division of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
Division of Obstetrics and Gynecology, Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy.
Front Oncol. 2022 Apr 8;12:818613. doi: 10.3389/fonc.2022.818613. eCollection 2022.
Radical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis.
We analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis.
High levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively.
The preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings.
对原发性肿瘤进行根治性手术切除并联合单/双侧腹股沟股淋巴结清扫术是浸润性外阴鳞状细胞癌（VSCC）的标准治疗方法，且该方法常与严重的发病率相关。调整手术治疗至关重要，全面的术前评估必不可少。血管内皮生长因子D（VEGF-D）被认为是参与肿瘤通过淋巴管扩散的淋巴管生成调节因子。本研究的目的是评估VEGF-D在预测腹股沟股淋巴结转移方面的潜力。
我们通过酶联免疫吸附测定法分析了两个独立的VSCC患者队列术前血清VEGF-D（sVEGF-D）水平，并通过免疫组织化学分析了其在肿瘤组织上的蛋白表达。进行逻辑回归以确定淋巴结转移的独立危险因素，并使用Cox比例风险模型进行生存分析。
高水平的sVEGF-D而非组织VEGF-D与腹股沟淋巴结阳性及更高级别的国际妇产科联合会（FIGO）分期显著相关。在多变量分析中，高sVEGF-D水平是淋巴结转移和预后较差的独立预测因素。基于sVEGF-D、活检评估的肿瘤分级、肿瘤直径和淋巴结临床评估的预测模型能够预测淋巴结转移，在训练队列和验证队列中的C指数值分别达到0.79和0.73。
术前sVEGF-D水平可能是预测VSCC患者淋巴结转移和预后的可靠生物标志物，有助于做出更好的临床/手术决策。需要多中心前瞻性研究来证实我们的发现。
