Prognostic value of vascular endothelial growth factor-C and podoplanin mRNA expression in esophageal cancer
ONCOLOGY LETTERS
Authors: Juchniewicz, Agnieszka; Niklinska, Wieslawa; Kowalczuk, Oksana; Laudanski, Wojciech; Sulewska, Anetta; Dziegielewski, Piotr; Milewski, Robert; Naumnik, Wojciech; Kozlowski, Miroslaw; Niklinski, Jacek
Abstract
Vascular endothelial growth factor-C (VEGF-C), VEGF-D, VEGF receptor-3 (VEGFR-3) and podoplanin (PDPN) are involved in the spread of cancer. The current study evaluated VEGF-C, VEGF-D, VEGFR-3 and PDPN mRNA expression levels in 84 esophageal cancer samples from patients who had undergone surgery according to reverse transcription-quantitative polymerase chain reaction, and correlated the results with the clinicopathological features. The effects on lymph node metastasis and survival were identified by performing univariate and multivariate analyses. VEGF-C, PDPN, VEGF-D and VEGFR-3 were overexpressed in 52.4, 52.4, 32.1 and 51.2% of esophageal cancer samples, respectively. Furthermore, the expression of VEGF-C and PDPN was significantly correlated with lymph node metastasis, depth of tumor invasion and tumor stage (P<0.05). Logistic regression analysis identified tumor size (P=0.001), depth of invasion (P=0.002) and PDPN mRNA expression (P=0.022) as significant multivariable predictors of regional lymph node metastasis. Upon univariate survival analysis, the depth of tumor invasion, lymph node metastasis, histological grade, tumor stage, tumor size, residual tumor, and VEGF-C and PDPN mRNA expression were identified to be significant independent prognostic factors for overall survival (OS) time. Additionally, multivariate analysis identified tumor size (P=0.049), residual tumor (P<0.001) and PDPN mRNA expression (P=0.02) as independent factors for poor OS time. Thus, it was concluded that PDPN mRNA expression may serve as predictor for regional lymph node metastasis, and that VEGF-C and PDPN may be prognostic factors in patients with resected esophageal cancer.
Podoplanin Lymphatic Density and Invasion Correlate With Adverse Clinicopathologic and Biological Factors and Survival in Neuroblastomas
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Authors: Ramani, Pramila; Somerville, Michelle S.; May, Margaret T.
Abstract
Neuroblastoma (NB) is a challenging problem in oncology, as the majority of patients have lymphatic and/or hematogenous metastases at diagnosis. We investigated the prognostic significance of lymphatic density (LD) and invasion (LI) in NBs using the lymphatic endothelial marker podoplanin (PDPN). A total of 77 neuroblastic tumors and 9 ganglioneuromas (GNs) were immunostained for PDPN using D2-40 antibody. Intratumoral lymphatics were identified in 87% (67/77) of NBs and 7/9 GNs. The LD counts were significantly higher (P < 0.01) in NBs (median = 19.6, range = 0.00 to 89.3) than in GNs (median = 10.2, range = 0 to 18.7). LI, assessed in D2-40-stained lymphatics, was present in 52/67 (78%) NBs. LDs were significantly higher in NBs from patients with adverse clinical factors (advanced-stage, high-risk group, primary abdominal compared with extra-abdominal sites), biological factors (MYCN amplification, 1p deletion, 17q gain), and distant lymph node metastases. LDs and LI were also significantly higher in NBs belonging to an unfavorable pathology prognostic group and in those with a high mitosis-karyorrhexis index. High LD and the presence of LI correlated with a shorter event-free survival in univariable analyses. High LD and the presence of LI were also associated with worse overall survival, although the association was less strong. In conclusion, increased LDs and the presence of LI correlated with adverse clinicopathologic and biological factors and survival. These findings suggest that PDPN has the potential to provide valuable prognostic information to clinicians for risk assessment in NBs.