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Sonic Hedgehog proteins are overexpressed in high- grade serous ovarian carcinomas

Sonic Hedgehog (SHH) protein, along with Indian Hedgehog (IHH) and Desert Hedgehog (DHH), is a ligand that activates Hedgehog signaling pathway (HH). It is an evolutionary conserved pathway that is necessary for normal embryonal development of diverse organisms, from fruit flies to humans. Whereas in adult human cells HH is largely inactive, it may become active following various tissue injuries that require reparation and regeneration of damaged cellular structures. Disruption in activation of this signaling pathway has been found in many types of human cancers indicating its important role in carcinogenesis. Since SHH is one of the activators of HH signaling pathway, the aim of this study was to define the pattern of SHH protein expression. This is essential for better understanding of proliferative, migratory and invasive potential of cells of human ovarian high-grade serous carcinoma and human ovarian benign serous tumors. Thus, expression of SHH ligands was analyzed by immunohistochemistry and quantified using stereological method of tissue volume density (Vv ; mm0) estimation. We found statistically higher expression of SHH ligands in ovarian high-grade serous carcinoma (0.1122±0.01590) compared to ovarian benign serous tumors (0.02917±0.003564) (Mann-Whitney test ; p=0.0002), which indicates an increased activation of Hedgehog signaling pathway in carcinomas with high malignant potential. This result, i.e. an association between increased expression of SHH proteins and development of aggressive ovarian malignancy, points to potential important role of HH signaling pathway in ovarian tumorigenesis.

SHH ; Hedgehog signaling pathway ; Ovary ; Serous carcinomas ; Serous cystadenomas

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