Prognosis of METTL-14 in Endometrial Carcinoma

1. To evaluate immunohistochemical expression of METTL14 in type1 endometrial carcinoma. 2. To evaluate the correlation between METTL14 expression and clinicopathological parameters of patients with type 1endometrial carcinoma such as tumor grade, lymhovascular invasion, age of pateints, tumor stage, presence of myometrial invasion and presence of cervical stroma affection. 3. To assess correlation of METTL-14 expression with disease free survival and overall survival.

Endometrial cancer(EC) is the second most common gynecologic cancer worldwide(1). In Egypt its incidence rate has increased in recent years, reaching 4.1 per 100,000 women(2). The most common histological subtype is endometrioid adenocarcinoma(3). Endometrial carcinoma can be divided into:Type I and Type II tumors. The incidence of Type I is 60-80% and that of Type II is 20%(4). N6-methyladenosine (m6A)is the most abundant RNA modification in mammalian mRNA and has a crucial role in the occurrence and development of various diseases, particularly malignant tumors(3). Many factors were found to affect the prognosis of endometrial carcinoma, one of these factors is m6A RNA methylation(5). This modification is dynamic and reversible, and it is catalyzed by three main types of regulators(3). It has been reported that m6A methylation was performed via methyltransferase complex regulators composed of "writer," "eraser," and "reader"(6). Methyltransferase like 14 (METTL14), a member of "writer", acts to regulate the occurrence of various cancers(7). In most tumors METTL14 acts as an antioncogene, regulating the RNA of genes that help the cell detect and repair DNA damage, acting as a protective mechanism against cancer. Reducing m6A mRNA may be due to METTL14 mutation. Reducing m6A mRNA levels in endometrial cancer cells could enhance cell proliferation and tumorigenicity in vitro and in vivo(8).The role of METTL14 as a risk factor in prognosis of endometrial carcinoma is still unknown.