Prognostic Significance of Lymphatic Vessel Density Detected by D2-40 and Its Relation to Claudin-4 Expression in Prostatic Adenocarcinoma

Abstract

Background. Lymphovascular invasion is an important pathway of metastatic spread and regional lymph node metastasis is the major prognostic factor in prostatic adenocarcinoma. D2-40 is used to identify the lymphatic vessels and to assess the lymphatic vessel density (LVD). Expression of claudin-4 may be related to invasion and progression of carcinoma cells in several primary tumors. Aim. To evaluate intra- and peritumoral LVD through immunohistochemical expression of D2-40 in relation to claudin-4 expression and clinicopathological parameters in prostatic adenocarcinoma. Materials and Methods. Immunohistochemical staining procedure was performed on 53 paraffin-embedded blocks of radical prostatectomy specimens for prostatic adenocarcinoma using anti D2-40 and claudin-4 antibodies. Sections were evaluated for mean LVD in intratumoral and peritumoral tissues assessed by D2-40 expression. Results. LVD in intratumoral tissues was significantly lower compared with peritumoral areas ( P = .0001). Peritumoral mean LVD was significantly higher in cases with lymphovascular invasion ( P = .041) and in cases with positive lymph node metastasis ( P = .003) than intratumoral mean LVD. High claudin-4 expression was significantly correlated with high tumor grade ( P = .0001), lymphovascular invasion ( P = .006), and positive lymph node metastasis ( P = .004). High claudin-4 expression was significantly associated with increased mean LVD in peritumoral tissues. Conclusion. Increased peritumoral mean LVD in prostatic adenocarcinoma is associated with lymphovascular invasion and positive lymph node metastasis. High claudin-4 expression is associated with high tumor grade, lymphocascular invasion, positive lymph node metastasis, and high mean peritumoral LVD suggesting that D2-40 and claudin-4 may represent different mechanisms of lymphatic vessel invasion with both biomarkers is related to poor prognosis.