FXYD3 Protein Expression And Its Clinicopathological Significance In Endometrial Cancers

Objective: Endometrial cancer derives from endometrial epithelial, accounts for 20% ~ 30% of female genital tract malignancies. Recent years, the incidence has upward and young trend, but the pathogenesis of endometrial cancer is still not very clear.FXYD3 is a member of the FXYD family of single transmembrane proteins that discovered recently and associated with small molecules (30~130 amino acid). The FXYD protein sequences are highly conserved through evolution, and are characterized by a 35-amino acid FXYD homology domain, which includes the short signature motif PFXYD (Pro, Phe, X, Tyr, Asp) and the transmembrane domain,contains seven invariant amino acids and six highly conserved amino acid sequence. PFXYD has been identification in most mammals, in addition to proline uncertainty in some spinal animals. The variable X is often the tyrosine amino acid, can also be Threo- nine, Glutamic or Histidine. FXYD family has seven members, except FXYD5, protein the others contains are less than 100 amino acids. It is reports that FXYD proteins family is small molecules transport channel or channel regulator, and it associate with structure and function of Na, K-ATPase. They are widely distributed in mammalian tissues. All of the genes are expressed early in fetal life. The most notable finding about the tissue distribution is the preponderance of tissues that perform ?uid and solute transport or that are electrically excitable, but it expressed in certain tissue.FXYD (Mat-8) was originally cloned from murine mammary tumors induced by the neu and ras ontogenesis but not by c-myc rint-2. Later research found that MAT-8 is similar to FXYD1 (phospholemman / PLM), so it was classified to FXYD family, named FXYD3 (domain-containing ion transport regulator 3 precursor). Since FXYD3 protein has been found in the house mouse, many researchers have been done by using various methods in human. That research showed that the FXYD3 can express not only in normal tissue such as the uterus, colon, stomach and skin, but also in some malignant tumor, even though found expression lever was positively correlated with the FXYD3. Interestingly, there are a number of studies that FXYD3 expression down-regulated in some cancers. However, to our knowledge, there is no study about the relationship between FXYD3 and endometrial cancer yet. In percent study, endometriosis carcinoma is thought to progress through a premalignant phase of intraendometrial neoplasia (atypical hyperplasia) in a large proportion of cases, therefore, we included premalignant lesions into the present study, and examined FXYD3 protein expression in the normal endometrium, atypical endometrial hyperplasia and endometrial cancer by immunohistochemistry, and originally explored its role in tumorigenesis and development of endometrial cancer and the relationship with clinicopathological features in patients of endometrial cancer.Method: S-P immunohistochemistry method was used to deteect expression of FXYD3 protein 21 cases of normal endometrium, 18 cases of atypical endometrial hyperplasia and 50 cases of endome- trial carcinoma. The paraffin tissue blocks were removed and serial sections 3, one for FXYD3 immunohistochemistry, two spare. The positive staining control was slices of breast cancer with FXYD3 positive staining. The PBS solution was choosing for negative control.Results:1 FXYD3 expression in the tissues of normal endometrial, atypical hyperplasia, endometrial cancerCompared with FXYD3 protein in endometrial carcinoma, atypical endometrial hyperplasia and normal endometrial tissues. The positive rate of FXYD3 (Mat-8) protein expression in endometrial cancer, atypical hyperplasia, normal endometrial respectively was 26.00 %, 22.22%, 0.00%. The trend ascended gradually. Significance among them was less than 0.05. (p﹤0.05) FXYD3 protein expression in endometrial cancer and endometrial atypical hyperplasia was not statistically significant (p> 0.05).2 The relationship between FXYD3 protein expression and clinical pathological featuresThe positive rate of FXYD3protein expression had no significant correlation with patient age, blood pressure, weight, blood glucose, family history, endometrial cancer staging, metastasis of lymph node, histology type, depth of invasion and pathology grade( p >0.05). But the positive rate of FXYD3 protein expression was associated with fertility frequency(p﹤0.05).Conclusion:1 FXYD3 protein in the formation of endometrial cancer were up-regulated, FXYD3 protein expression may be an early event in endometrial cancer formation. It is suggests that FXYD3 protein may could be plays an important role during the formation of one of the development of endometrial cancer invasion and metastasis. It can be used to guide clinical treatment.2 The positive rate of FXYD3 protein expression in endometrial cancer tissues with age, blood pressure, fertility, blood glucose, blood lipids, family background of cancer, clinical stage, growth pattern, histological type, pathological grade, myometrial invasion , Cervical involvement, lymph node metastasis was no significant correlation (P> 0.05). However, its expression was correlated with fertility and a woman who has more children, the expression of FXYD3 protein is poor and the chance of endometrial cancer would be lower. It is show that the FXYD3 protein may be related progesterone. Progesterone can inhibit its expression.