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.

Antiangiogenic effects of oridonin

“…Claudin 1 and Claudin 7 can be used in cancer diagnosis and treatment [56]. Claudin 4 has a correlation with tumour angiogenesis, and can be used as a treatment target protein, which was consistent with our research results [52, 53]. Moreover, the research conformed that Claudin 4 and VEGFA, VEGFR2, VEGFR3, and TP53 were all contributed to the anti-tumour effect based on the inhibition of angiogenesis (Fig 16…”

Diagnostic Value of Claudin-4 and EZH2 Immunohistochemistry in Effusion Cytology

“…Naso (2020) assessed claudin-4 immunoreactivity in surgical specimens of lung tumors, and reported positivity in 87% of lung adenocarcinomas. Furthermore, claudin-4 was reported by separate reports in most cases of endometrial, breast, gastric, prostatic and ovarian carcinomas (Pan et al, 2013;Abd-Elazeem and Abd-Elazeem, 2015;Shareef et al, 2015;Radi and Abd-Elazeem, 2016;Martín de la Fuente et al, 2018).…”

Tight Junctions and Prostate Cancer

“…The authors explain the diminished claudin 4 expressions in higher Gleason score group by diminished cohesion and organisation of cells in high grade tumors [100]. In another study claudin 4 expression was associated with mean vascular density in prostate cancer [101]. Claudin 4 expression was also associated with a high tumor grade, lymphovascular invasion and lymph node metastasis [101] Claudin 2, 3 and 5 expressions are higher in prostate adenocarcinoma compared to prostate hyperplasia while some investigators report lower or higher claudin 4 expressions [102,88].…”

“…In another study claudin 4 expression was associated with mean vascular density in prostate cancer [101]. Claudin 4 expression was also associated with a high tumor grade, lymphovascular invasion and lymph node metastasis [101] Claudin 2, 3 and 5 expressions are higher in prostate adenocarcinoma compared to prostate hyperplasia while some investigators report lower or higher claudin 4 expressions [102,88]. Claudins 1 and 7 showed a similar level in both conditions while claudin 11 was not detected in prostate epithelial cells [102].…”