Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

Abstract

Abstract:The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90-97) Key words: esophageal cancer, lymphatic vessel invasion, podoplanin, D2-40, lymph node metastasis, prognosis ageal cancer. More than 65% of patients with localized esophageal cancers and negative resection margin have a positive lymph node at the time of surgery [1]. However, despite complete tumor resection and extensive lymphadenectomy, systemic and local recurrence is common [2] and the five-year survival rate is 15-39% [3].The discovery over the last decade of markers of lymphatic endothelial cells like podoplanin (D2-40) [4], LYVE-1 [5] and Prox 1 [6], and the development of novel antibodies to these markers, have generated

THORACIC SURGERY Intratumoral lymphatic vessel density, and intratumoral and peritumoral lymphatic vessel invasion as predictive factors of lymph node metastasis and prognostic factors in esophageal cancer

“…Imamura et al [17], using D2-40 staining, revealed that positive LVI correlated with worse prognosis in univariate analysis and was an adverse independent prognostic factor for overall survival in patients classified as node negative. Our earlier study found that LVI in the entire tumor is an independent prognostic factor of both disease-free survival and overall survival [23]. This study's results show that positive itLVI and ptLVI, like lymph node metastasis, tumor depth, stage, and positive resection margin, are significantly associated with worse disease-free survival, cancer-specific survival and overall survival in univariate and multivariate analyses.…”

“…Lin et al [22] have reported similar observations for colorectal cancer. Imamura et al [17], Tomita et al [18] and our earlier study [23] revealed that LVI in the entire tumor tissue of esophageal cancer was significantly linked with nodal metastasis. In contrast, Mori et al [15] found that only ptLVI positively correlated with lymph node metastasis.…”

Lymphangiogenesis and biological behavior in pancreatic carcinoma and other pancreatic tumors

“…Lymphatic vessels are the main pathways for the spread of tumor cells to regional lymph nodes (3,4,8–12). The shape of lymphatic vessels is very similar to that of small veins, making it difficult to distinguish lymphatic from blood vessels when they are invaded and destroyed (8).…”

“…Research into the mechanism of tumor metastasis has primarily focused on vascular vessels, with little focus on lymphatic vessels. Lymphatic vessels are important pathways for metastasis and are a primary cause of post-operative tumor recurrence (1,3,6,8). Therefore, it is of great clinical and physiological significance to discover the molecular mechanisms underlying tumor development and metastasis through lymphatic vessels and to explore ways of preventing tumor lymphatic metastasis.…”

Prognostic value of vascular endothelial growth factor-C and podoplanin mRNA expression in esophageal cancer

“…PDPN has previously been used to assess lymphatic vessel density and invasion in various types of cancer, including esophageal carcinoma (10,11). Thus, it may act as a mediator of tumor cell invasion and metastasis (12).…”