Lymphatic vessel invasion detected by the D2-40 monoclonal antibody is an independent prognostic factor in node-negative esophageal squamous cell carcinoma.

D2-40 staining has been reported to be useful for both identifying lymphatic vessel invasion (LVI) and counting lymphatic vessel density (LVD) in various cancers. The aim of this study was to clarify the prognostic significance of D2-40 staining in patients with esophageal squamous cell carcinoma (ESCC). A total of 159 consecutive patients with ESCC who underwent an esophagectomy with lymph node dissection were eligible. LVI was diagnosed by both hematoxylin-eosin (LVI-HE) and D2-40 staining (LVI-D2-40) in the largest central sections of the entire tumors, while both the intratumoral and peritumoral LVD were counted by D2-40 staining. The correlation between the prognosis and clinicopathological factors was investigated. An univariate analysis revealed that tumor invasion beyond the muscularis propria, lymph node metastasis (LNM), LVI-HE, LVI-D2-40, high intratumoral LVD, and blood vessel invasion correlated with worse patients' prognosis (P < 0.05). A multivariate analysis revealed LNM to be the only independent prognostic factor in all cases (P = 0.0083). On the other hand, when the prognostic factors of 83 patients without LNM were investigated, LVI-D2-40 was revealed to be the only independent prognostic factor (P = 0.048). LVI detected by D2-40 staining was an independent prognostic factor in patients with node-negative ESCC.

Imamura Y ，Watanabe M ，Nagai Y ，Baba Y ，Hirashima K ，Karashima R ，Iwatsuki M ，Yoshida N ，Kinoshita K ，Kurashige J ，Iyama K ，Baba H ... -  《-》

Clinical significance of peritumoral lymphatic vessel density and lymphatic vessel invasion detected by D2-40 immunostaining in FIGO Ib1-IIa squamous cell cervical cancer.

Xiong Y ，Cao LP ，Rao HL ，Cai MY ，Liang LZ ，Liu JH ... -  《-》

Detection of lymphovascular invasion in vulvar cancer by D2-40 (podoplanin) as a predictor for inguinal lymph node metastases.

Lymphatic vessel invasion (LVI) plays a major role in the spread of vulvar cancer and predicts regional lymph node metastasis. D2-40, a monoclonal immunohistochemical marker might be able to increase the detection rate of LVI compared to conventional hematoxylin-eosin (HE) staining. The aim of the study was to evaluate the suitability of D2-40 for the prediction of regional lymph node metastases. Immunohistochemical staining with D2-40 was performed on formalin-fixed, paraffin-embedded tissue sections of 32 patients with squamous cell carcinoma of the vulva. Slides were screened for the presence of LVI. Correlation with clinico-pathological features including LVI as retrieved by routine HE-stained sections was assessed. Immunostaining with D2-40 significantly (p = 0.019) increased the frequency of detection of lymphatic invasion compared to conventional HE staining. LVI was correctly identified by D2-40 (D2-40+ LVI) in 65.6% of tumor specimens as compared to 40.6% by routine HE staining (HE+ LVI). D2-40+ LVI significantly (p = 0.026) predicted inguinal lymph node metastases. Immunostaining with D2-40 significantly increased the frequency of detection of lymphatic invasion compared to conventional HE staining in squamous cell carcinomas of the vulva. D2-40+ LVI is a strong predictor for inguinal lymph node metastases.

Braun M ，Wardelmann E ，Debald M ，Walgenbach-Bruenagel G ，Höller T ，Wolfgarten M ，Sauerwald A ，Rudlowski C ，Büttner R ，Kuhn W ，Pölcher M ... -  《-》

Intratumoral lymphatics and lymphatic vessel invasion detected by D2-40 are essential for lymph node metastasis in bladder transitional cell carcinoma.

Bladder cancer is frequently associated with regional lymph node metastasis at the time of diagnosis or after initial treatment, and lymph node metastasis is crucial for clinical therapeutic strategies. Lymphangiogenesis, detected by antibodies specific for lymphatic endothelial cells, is correlated with cancer spread, but the mechanisms that underlie lymphatic spread and the role of lymphangiogenesis in cancer metastasis has been less clear. The aim of this study was to investigate the association of vascular endothelial growth factor (VEGF)-D expression, intratumoral lymphatics, and lymphatic invasion associated with lymph node metastasis as well as the prognostic analysis in patients with bladder transitional cell carcinoma (TCC). The VEGF-D expression was evaluated by immunohistochemistry in 72 specimens, and tumoral lymphatic vessels were measured by D2-40. Counts of lymph vessels were taken in intratumoral and peritumoral areas. Survival analyses and their independent roles were investigated using univariate and multivariate analysis models. The high expression of VEGF-D was closely associated with the intratumoral lymphatic vessels, tumoral lymphatic invasion, and lymph node metastasis as well as a shorter overall survival. Higher lymphatic vessel density, intratumoral lymphatics, and lymphatic invasion showed a significant association with lymph node metastasis. Univariate analysis indicated that VEGF-D, intratumoral lymphatics, and lymphatic invasion were associated with overall survival, but they were not independent prognostic factors for bladder TCC in multivariate analysis. We conclude that VEGF-D plays an essential role in tumoral lymphangiogenesis. Intratumoral lymphatics and lymphatic invasion are important predictive factors of pelvic lymph node metastasis in patients with bladder cancer.

Ma Y ，Hou Y ，Liu B ，Li X ，Yang S ，Ma J ... -  《-》

Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases.

Adachi Y ，Nakamura H ，Kitamura Y ，Taniguchi Y ，Araki K ，Shomori K ，Horie Y ，Kurozawa Y ，Ito H ，Hayashi K ... -  《PATHOLOGY INTERNATIONAL》