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解析口腔鳞状细胞癌中的淋巴管生成:重点关注区域性转移的临床和组织病理学决定因素。

Decoding lymphangiogenesis in oral squamous cell carcinoma: Emphasis on clinical and histopathological determinants of regional metastasis.

机构信息

Department of Oral Pathology, Microbiology and Forensic Odontology, Dental Institute, RIMS, Ranchi, Jharkhand, India.

Department of Anatomy, RIMS, Ranchi, Jharkhand, India.

出版信息

PLoS One. 2024 Nov 14;19(11):e0311108. doi: 10.1371/journal.pone.0311108. eCollection 2024.

DOI:10.1371/journal.pone.0311108
PMID:39541328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11563478/
Abstract

PURPOSE

The growth and metastasis of solid epithelial tumors is lymphangiogenesis dependent. The most important lymphangiogenic inducers facilitating this progression is Vascular endothelial Growth Factor C (VEGF-C). The recent D2-40 (Podoplanin) antibody is specific for lymphatic epithelium and allows its objective assessment. Also, lymphovascular invasion (LVI) is a risk factor for lymph node metastases (LNM) and indicates a significant influx of tumor cells into the lymphatics, causing regional metastasis. Thus, the following study was conducted to assess and correlate VEGF-C and D2-40 immunoexpressions with clinical and histopathologic lymph node status in Oral Squamous Cell Carcinoma (OSCC) cases and also to estimate the impact of intratumoral (ILVD) and peritumoral lymphatic vessel density (PLVD) in such cases.

METHODOLOGY

A total of 128 OSCC cases, divided as Group I: Cases with clinically and histopathologically negative lymph nodes (n = 64) and Group II: Cases with clinically negative but histopathologically positive lymph nodes (n = 64) were immunoscored for VEGF-C (Anti VEGF-C antibody) (PA5-29772, Invitrogen) and D2-40 (Anti D2-40 antibody) (IR072/8072, Dako) using standard protocols. The data was statistically evaluated using STATA 18.0 with p≤0.05 considered statistically significant throughout the study.

RESULT

21.88% Group I cases and 40.62% Group II cases showed highest immuno-positivity for VEGF-C (p = 0.00). The mean D2-40 score for Intratumoral Lymphatic Vessel Density (ILVD) and Peritumoral Lymphatic Vessel Density (PLVD) was higher for group II cases (i.e., 41.5±13.73 and 35.95±8.27 respectively at 95% CI, p = 0.00) suggesting a direct correlation between Lymphatic Vessel Density (LVD) and LNM.

CONCLUSION

Lymphangiogenesis is a true determinant of the biologic potential of OSCC and obtaining an objective data in terms of LVD through D2-40 could be impactful in OSSC diagnosis and guiding treatment decisions by clinicians.

摘要

目的

实体上皮肿瘤的生长和转移依赖于淋巴管生成。促进这一进展的最重要的淋巴管生成诱导因子是血管内皮生长因子 C(VEGF-C)。最近的 D2-40(Podoplanin)抗体是淋巴管上皮的特异性抗体,允许对其进行客观评估。此外,淋巴血管侵犯(LVI)是淋巴结转移(LNM)的危险因素,并表明肿瘤细胞大量进入淋巴管,导致区域性转移。因此,进行了以下研究,以评估并将 VEGF-C 和 D2-40 的免疫表达与口腔鳞状细胞癌(OSCC)病例的临床和组织病理学淋巴结状态相关联,并估计肿瘤内(ILVD)和肿瘤周围淋巴管密度(PLVD)对这些病例的影响。

方法

总共 128 例 OSCC 病例,分为 I 组:临床和组织病理学上淋巴结阴性的病例(n=64)和 II 组:临床淋巴结阴性但组织病理学上淋巴结阳性的病例(n=64),使用标准方案对 VEGF-C(抗 VEGF-C 抗体)(PA5-29772,Invitrogen)和 D2-40(抗 D2-40 抗体)(IR072/8072,Dako)进行免疫评分。使用 STATA 18.0 对数据进行统计学评估,整个研究中 p≤0.05 被认为具有统计学意义。

结果

21.88%的 I 组病例和 40.62%的 II 组病例的 VEGF-C 免疫阳性率最高(p=0.00)。II 组的 D2-40 评分在肿瘤内淋巴管密度(ILVD)和肿瘤周围淋巴管密度(PLVD)方面较高(分别为 41.5±13.73 和 35.95±8.27,95%CI,p=0.00),表明淋巴管密度(LVD)与 LNM 之间存在直接相关性。

结论

淋巴管生成是 OSCC 生物学潜力的真正决定因素,通过 D2-40 获得 LVD 的客观数据可能对 OSCC 的诊断和指导临床医生的治疗决策产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbf1/11563478/ce917f73cf68/pone.0311108.g007.jpg
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