Expression of Semaphorin 3F and Its Receptors in Epithelial Ovarian Cancer, Fallopian Tubes, and Secondary Müllerian Tissues

Abstract

While semaphorins and their receptors appear to play a role in tumor carcinogenesis, little is known about the role of semaphorin 3F (S3F) in epithelial ovarian cancer (EOC) development. Therefore, we sought to determine the clinical relationship between S3F and its receptors, neuropilin-2 (NP-2) and neuropilin-1 (NP-1) with EOC progression. We analyzed the immunohistological expression of S3F, NP-2, and NP-1 in clinical specimens of normal ovaries (N), benign cystadenomas (Cy), well-differentiated adenocarcinomas (WD), poorly-differentiated adenocarcinomas (PD), inclusion cysts (IC), paraovarian cysts (PC), and fallopian tubes (FT). Tissue sections were evaluated for staining intensity and percentage of immunoreactive epithelia. We found that expression of S3F and NP-2 decreased while NP-1 expression increased with EOC progression. Interestingly, we also found elevated expression of S3F, NP-2, and NP-1 in epithelia of ICs, PCs, and FT. Our findings indicate that loss or deregulation of semaphorin signaling may play an important role in EOC development.

Figure 1

S3F expression decreases while NP-1 increases with epithelial ovarian cancer progression. Representative illustrations of immunohistochemical staining of normal (N), serous cystadenoma (Cy), well-differentiated (WD) and poorly differentiated (PD) serous adenocarcinomas) for S3F, NP-2, and NP-1. Placental tissue was used for positive control (C) and arrow indicates expression of S3F by endothelial cells. Primary antibodies were replaced with non-immune serum in negative control sections (inset). Original magnification: 400×.

Figure 2

Graphical depiction of S3F, NP-2, and NP-1 expression with epithelial ovarian cancer progression. Immunohistochemically stained sections of normal (N), serous cystadenomas (Cy), well-differentiated (WD) and poorly differentiated (PD) serous adenocarcinomas were evaluated for expression of S3f, NP-2 and NP-1 and scored as negative, weak, moderate, or strong as described in Materials and Methods.

Figure 3

NP-2 expression occurs in distinct clusters of tumor cells. Representative illustration of NP-2 expression in well-differentiated serous adenocarcinoma (WD). Original magnification is 100× and inset is 200×.

Figure 4

S3F expression is elevated in inclusion cysts, paraovarian cysts, and fallopian tubes. Representative illustrations of immunohistochemical staining of normal ovary (N), inclusion cyst (IC), paraovarian cyst (PC), and fallopian tube (FT) for S3F, NP-2, and NP-1. Original magnification is 400×.

Figure 5

Graphical depiction of S3F, NP-2, and NP-1 expression in inclusion cysts, paraovarian cysts, and fallopian tubes compared to normal ovaries. Immunohistochemically stained sections of normal ovary (N), inclusion cysts (IC), paraovarian cysts (PC) and fallopian tubes (FT) were evaluated for staining intensity and designated as negative, weak, moderate, or strong following staining with antibodies directed against S3F, NP-2, and NP-1.