Aberrant Methylation And The Expression Of The Human Hedgehog Interacting Protein(HHIP) Gene In Endometrial Carcinoma

Endometrial carcinoma is one of the most common malignancies in female genital tract. It accounts for 7% of all the female cancer, and 20% to 30% of all the malignancies in female genital tract. In the recent years, the morbidity of endometrial carcinoma has been growing rapidly all around the world, and the age of the patients diagonized with this disease is younger than before. Endometrial carcinoma do harm to the health and the life of women. The mechanisms of the occurrence and the development of endometrial cancer and the method of diagnosis and treatment of endometrial cancer are still important issues to be resolved.The hedgehog signaling pathway can be find in the creature from low levels to high levels. Hedgehog signaling pathway is essential in embryonic patterning, cell differentiation and cell proliferation. Recently, some studies have revealed that the activation of hedgehog signaling pathway may be involved in the occurrence and the development of cancer.Hedgehog interacting protein(HHIP) is a negative regulator of hedgehog signaling pathway. HHIP suppresses the activation of the hedgehog signaling. Some reaserches have shown that aberrant methylation of the HHIP promoter CpG island may cause the silencing of the HHIP, so that the hedgehog signaling pathway is over activated. This machanism may be involved in the occurrence and the development of the cancer. The relationship between HHIP and endometrial carcinoma has not been reported yet.Objective: To investigate the aberrant methylation and the expression of Hedgehog Interacting Protein (HHIP) gene in endometrial carcinoma, and to explore the possioble relationship between the methylation of the gene and the expression of the gene and their effect on the cause and the proliferation of the endometrial carcinoma. To summerize some newfound about hedgehog signaling pathway in the malignancies especially in female genital tract malignancies. To summerize the recent reaserches about the relationship between HHIP and cancer.Methods: The promoter methylation status of HHIP gene was tested by methylation-specific PCR in 20 normal endometrium tissus and 30 endometrial carcinoma tissus. The expression of HHIP was studied by histochemisty in 20 cases of normal endometrium and 30 cases of endometrial carcinoma.The correlation between the methylation status and endometrial carcinoma ,the correlation between the HHIP silencing and endometrial carcinoma as well as the correlation between the methylation status and the silencing of HHIP were tested by SPSS 13.0.Results: The frequencies of hepermethylation of Hhip in normal endometrium tissues were 0%(0/20), while the frequencies of heper -methylation of Hhip in endometrial carcinoma tissue were 40%(12/30). The methylation rate in endometrial carcinoma tissue was higher than the methylation rate in normal endometrium tissue.All the normal endometrium tissues showed positive staining pattern of Hhip protein(20/20).40%(8/20) of endometrial carcinoma tissues showed positive staining pattern of HHIP protein. In endometrial cancer, the HHIP protein silencing was easier to be found than in the normal endometrium tissue.The hepermethylation of HHIP gene was not related with the expression of HHIP protein(p>0.05).Conclusion: HHIP is related to the occurrence and the development of the endometrial carcinoma. The methylation rate in endometrial carcinoma tissue is higher than the methylation rate in normal endometrium tissue. In endometrial cancer, the HHIP protein silencing is easier to be found than in the normal endometrium tissue. The methylation of the HHIP gene promoter may be related to the silencing of the expression of the protein to some extent , and it may be involved in the occurrence of the endometrial carcinoma. However, methylation may not be the only reason for the silencing of the expression of HHIP, and other mechanisms remain to be revealed.