Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Abstract

The mechanism by which neuropilin-1 (NRP-1) induces malignancy in Epithelial Ovarian Cancer (EOC) is still unknown. This study is the first to demonstrate the relationship between NRP-1 expression and EMT markers vimentin, N-cadherin, E-cadherin and Slug. We used tissue microarrays containing the three main subtypes of EOC tumors: serous, mucinous cystadenocarcinoma and endometrioid adenocarcinoma and representative cases retrieved from our pathology archives. Immunohistochemistry was performed to detect the expression levels and location of NRP-1 and the aforementioned EMT proteins. NRP-1 was mainly expressed on cancer cells but not in normal ovarian surface epithelium (OSE). The Immunoreactive Scoring (IRS) values revealed that the expression of NRP-1, Slug and E-cadherin in the malignant subtypes of ovarian tissues was significantly higher (5.18 ± 0.64, 4.84 ± 0.7, 4.98 ± 0.68, respectively) than their expression in the normal and benign tissues (1.04 ± 0.29, 0.84 ± 0.68, 1.71 ± 0.66, respectively), with no significant differences among the studied subtypes. Vimentin was expressed in the cancer cell component of 43% of tumors and it was exclusively localized in the stroma of all mucinous tumors. The Spearman’s rho value indicated that NRP-1 is positively related to the EMT markers E-cadherin and Slug. This notion might indicate that NRP-1 is a partner in the EMT process in EOC tumors.

N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes

“…Regarding moderately differentiated SCC we observed high (9 cases, 56.3%) and low expression (7 cases, 43.8%). Many previous studies on OSCCs, ovarian cancer, tongue SCCs [4,37,39] reported similar finding.…”

“…[49] Sirin et al had observed similar finding in ovarian carcinoma as N-cadherin had no significant relationship with tumor grade. [39] N-cadherin expression was significantly related to tumor stage (p < .05) as 69.4% of HNSCCs with advanced TNM stage demonstrated high expression of N-cadherin. Similar to our finding was observed by Sirin et al [39] in ovarian cancer, Krisanaprakornkit et al [37] in tongue SCCs, Domenico et al in OSCCs.…”

“…[39] N-cadherin expression was significantly related to tumor stage (p < .05) as 69.4% of HNSCCs with advanced TNM stage demonstrated high expression of N-cadherin. Similar to our finding was observed by Sirin et al [39] in ovarian cancer, Krisanaprakornkit et al [37] in tongue SCCs, Domenico et al in OSCCs. [5] Increased incidence of recurrence and death also demonstrated significant correlation with N -cadherin expression…”

Neuropilin-1 Associated Molecules in the Blood Distinguish Poor Prognosis Breast Cancer: A Cross-Sectional Study

“…Additionally, numerous transcriptional regulators act downstream of NRP-1 such as SNAI1 17 , a transcriptional repressor pivotal for cell differentiation and survival that reverses the tumor suppressive effects induced by TGFβ1 in early stage breast cancer 18 . In a previous study on ovarian cancer we showed that NRP-1 had a positive relation to EMT markers 19 .…”

Novel regulatory role of neuropilin-1 in endothelial-to-mesenchymal transition and fibrosis in pancreatic ductal adenocarcinoma

“…Furthermore, PDAC is characterized by aberrant expression of NRP-1 [45, 60, 61], often correlated with tumor progression and poor patient prognosis [62]. Interestingly, recent evidences have implicated a novel regulatory role of NRP-1 in epithelial-to-mesenchymal transition (EMT); an evolutionary conserved developmental process, which is evoked during tumor invasion and metastasis of several cancers [63, 64]. Similarly, recent studies suggest that endothelial-to-mesenchymal transition (EndMT), which is originally observed during heart development, has a major role in pathological settings of cancer and fibrosis [21–25, 31].…”