Immunohistochemical Evaluation of Protein P16 Expression in Ovarian Germ Cell Tumors.
Ovarian germ cell tumors (OGCTs) constitute 10% of ovarian tumors in Egypt [1] and mainly affect young females [2].Teratomas are the most common type [3].Most of teratomas is benign. However, it is liable for malignant transformation [4]. Others are malignant including dysgerminoma, immature teratoma, yolk sac tumor,.etc.[5] and accounts 1-1.5% of cancers in young females [6]. The pathogenesis of OGCTs is not clearly understood. Some authors revealed that mature cystic teratoma is a form of human parthenogenesis [7], which makes important concerns about future of fertility and germ stem cell replacement therapy [8]. P16 is a member of cyclin-dependent kinase (CDK) inhibitors. It arrests the cell cycle in G1 phase, so it is known as a tumor suppressor protein [9]. CDK inhibitors now are evolving as novel target therapies under clinical trials such as Palbociclib, Abemaciclib and Ribociclib that offer a hope for different cancers, such as breast cancer [10] and non-small cell lung cancer [11].One member which is recently approved by US FDA is palbociclib for use in postmenopausal women with breast cancer [12].Thus, it is necessary to do further researches on its expression among different neoplasms. P16 immunohistochemical(IHC) expression has been widely investigated in different cancers. Its IHC expression is either absent [13] or overexpressed [14] .Overexpression of p16 is documented in Human Papilloma Virus related endocervical neoplasms and High grade squamous intraepithelial lesions of the vulvovaginal region [14].Absence of p16 expression is detected in multiple cancers such as Lung cancer, colorectal cancer and lymphoma [15]. P16 IHC expression in OGCTs is poorly investigated. One study suggests that absent p16 is involved in proliferation of malignant OGCTs via molecular assessment[16].Another study suggested that decrease P16 is involved in malignant transformation of Mature cystic teratoma to squamous cell carcinoma [17].However, Previous studies are still limited and recommended further studies to confirm its results. As the role of altered P16 protein in OGCTs is not widely investigated, we hypothesized that abnormal P16 expression may be involved in its pathogenesis and germ stem cell proliferation. Abnormalities may be found either in neoplastic or stromal components. The role of stromal component of OGCTs as tumor microenvironment has no published studies yet. This will give more information about molecular pathways of germ stem cell proliferation to give a hope for CDK inhibitors as novel target therapies in the management of OGCTs and new advances in use of germ stem cell replacement therapy.
Start: December 2019
Get Well Soon