Intratumoral Lymphatic Vessel Density in Vulvar Squamous Cell Carcinomas

Abstract

Lymphatic vessels serve as major routes for regional dissemination, and therefore, lymph node status is a key indicator of prognosis. To predict lymph node metastasis, tumor lymphatic density and lymphangiogenesis-related molecules have been studied in various tumor types. To our knowledge, no previous studies have evaluated the role of intratumoral lymphatic vessel density (LVD) in the behavior of vulvar carcinomas. The aim of this study was to analyze intratumoral LVD in relation to patient survival and well-characterized prognostic factors for cancer. Thirty-five patients with vulvar squamous cell carcinoma underwent vulvectomy and dissection of regional lymph nodes. Clinical records were reviewed, in addition to histological grade, peritumoral lymphatic invasion, and depth of infiltration for each case. Tissue microarray paraffin blocks were created, and lymphatic vessels were detected using immunohistochemical staining of podoplanin (D2-40 antibody). Intratumoral LVD was quantified by counting the number of stained vessels. Higher values for intratumoral LVD were associated with low-grade and low-stage tumors, and with tumors without lymphatic invasion and reduced stromal infiltration. In a univariate analysis, high intratumoral LVD was associated with a higher rate of overall survival and a lower rate of lymph node metastasis. Our results suggest that increased intratumoral LVD is associated with favorable prognosis in vulvar squamous carcinomas.

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

“…In our previous experience with cancers of the vulva, cervix and endometrium, we found an inverse correlation between intratumoral LVD and lymph node metastasis and prognosis 9-11. To explain our previous results, we hypothesized that the intratumoral lymphatic vessels were non-functional and therefore had the potential to disturb local drainage, including the transport of neoplastic cells outside the tumor.…”

“…The quantification of LVD was performed as previously described by our group 9-11. Briefly, stained TMA histologic sections were analyzed using standard light microscopy (Nikon, Eclipse 200).…”

Head and neck squamous cell carcinoma lymphatic spread and survival: Relevance of vascular endothelial growth factor family for tumor evaluation

“…Podoplanin is a glycoprotein that is recognized by the monoclonal antibody D2–40, which is considered the most reliable marker of lymphangiogenesis . Zhao et al examined podoplanin expression in OSCC and reported the proliferation of intratumoral and peritumoral lymphatics, suggesting that the spread of metastatic cells also occurs via intratumoral vessels.…”

“…Podoplanin is a 38-kDa membrane glycoprotein that is recognized by the monoclonal antibody D2-40, which has been used in research and clinical practice to distinguish lymphatic endothelium from endothelial cells of blood vessels (the latter does not express podoplanin). 14,18,22,23 Patients with a high lymphatic vessel density (LVD) are at increased risk for lymph node metastasis, supporting the hypothesis that LVD mediates lymphatic spread in oral carcinoma. 17,21,22,24 Based on findings that metastatic spread of head and neck tumors usually occurs via the lymphatic system and because lymphangiogenesis studies in various cancers have generated contradictory results, we measured the expression of lymphangiogenesis markers in HNSCC by immunohistochemistry.…”

“…One of the most reliable markers that is used to determine the presence of lymphatic vessels is podoplanin. Podoplanin is a 38‐kDa membrane glycoprotein that is recognized by the monoclonal antibody D2‐40, which has been used in research and clinical practice to distinguish lymphatic endothelium from endothelial cells of blood vessels (the latter does not express podoplanin) . Patients with a high lymphatic vessel density (LVD) are at increased risk for lymph node metastasis, supporting the hypothesis that LVD mediates lymphatic spread in oral carcinoma …”