Expression And Clinical Significance Of LKB1Protein In Endometrial Cancer Tissue

Objective:Endometrial carcinoma is one of the three commonmajor malignant tumor in female reproductive system, accounts for about20%~30%of female malignant tumor in reproductive tract. The high age of onsetfor60-65years old. Because of human life extension and obese peopleincreasing, its incidence increasing year by year in the world scope.It seriouslyendangers human health.In1983years Bohkman first divided this disease intotwo kinds: the estrogen dependent for typeⅠ,and the estrogen independentfor type Ⅱ. According to the different pathological classification, most oftypeⅠare endometrial adenocarcinoma, while typeⅡare the endometrialnon-adenocarcinoma (special pathological type). Further research found that:two kinds of endometrial cancer has completely different pathogenesis andbiological behaviour. Type Ⅰ thatbe related to estrogen, is the most common,and obesity and surround post-menopausal women are likely to develop thistype. Atypical hyperplasia of endometrium are the pre-cancerous lesions oftype I that infiltration of muscular layer be shallow, and histologic type bemore lining sample and mucoid with estrogen receptor (PR),progesteronereceptor(ER)positive, and the disease progresses slowly, better prognosis.TypeⅡthat is not rely on estrogen, more happen in postmenopausal women,and endometrial intraepithelial cancer (EIC) is the prophase lesions. Tumordifferentiation of TypeⅡ that infiltrate muscle layer deeply is bad,and itshistologic type are serous/clear cell carcinoma, or other special type, withPR,ER negative, malignant highly. This type endometrial cacinomor developfast, poor prognosis.The occurrence of endometrial cancer not only connect with sex hormonebut relate to receptors, and they are closely relates to oncogene, tumorsuppressor genes,DNA repair gene. The estrogen and its receptors as a kindof cells signals work in initiating tumor-increasing and developing each stage.The transmission of various sex hormone signals are regulated by gene.The different expression of all kinds of genes that be related to cancer canadjust the role of hormone and its receptors, promoting the occurrence anddevelopment of cancer. In recent years with the development of molecularbiology technology, and with the further research of genomics and proteomics,people realize that cancer is gene disease, and there are three special kinds ofgenes (namely oncogene, tumor-suppressor genes, DNA repair genes)participate in the occurrence and development of cancer. Therefore, theknown to gene that is related to endometrial carcinoma in occurrence anddevelopment is still the key to prevente and control endometrial carcinoma.LKB1/STK11(serine/threonine protein kinase11) is considered to be akind of tumor suppressor genes. In1998Hemminki and other people foundthe gene of LKB1/STK11extractted from blood cell of patients withPeutz-Jeghers syndromes (PJS) using the method of Positionaling CandidateCloning. The lacking of the wild type of LKB1gene in the polyps gene of PJScell result in activating expression of LKB1gene, it closely related to thathamartoma and adenomas development to cancerous. LKB1gene locating in19p13.13belt, cDNA span2158bp, coding areas1302bp, has nine explicitson. The LKB1is serine-threonine protein kinase of60kD that composed of433amino acids, containing a kinase region (in50~337anticodon). The Nregion contains a signal area of cell nucleus and cytoplasm positioning.LKB1gene expresses in all the tissue of fetus and adults, especiallyexpressing strongestly in adult skin,testicular fine tubular and the liver. Theexpression of LKB1is higher in fetal tissue than adults, and the inactivation ofLKB1in the tumor tissue may have a close relationship with the occurrenceand development of multiple tumors. The purpose of this research onexpression of LKB1in normal endometrium tissue, atypical hyperplasiaendometrium and endometrial cancer, is to explore the functions andsignificance of LKB1in the occurrences and development of endometrialcancer.Methods:All the specimens were collected from the patients with myoma of uterus/atypical hyperplasia endometrium/endometrial cancer, at theDepartment of Obstetrics and Gynecology in number Tree/Two/Four Hospitalof He Bei Medical University from September2009to September2011.According to the pathologic result,choose three groups: normal endometriumgroup (30cases), atypical hyperplasia group (10cases), endometrial cancergroup (30cases), Apply the method of immunohisto chemical S-P to detectthe expression of LKB1in each group.Statistical analysis was performed usingthe Statistical Package of Social Science13.0for Windows. Differencesbetween groups were analyzed by the chi-square. P values less than0.05wasconsidered statistically signicant.Results: The protein of LKB1in normal endometrium group is stronglypositive, the rate of expression100%(30/30). The rate of expression in theatypical hyperplasia of endometrium group is40%strongly positive and60%weakly positive. While the rate of expression in endometrial cancergroup is23.3%weakly positive, and the others all expressed negatively. Therate of expression of LKB1in the normal group,atypical hyperplasia groupand endometrial cancer group decended gradually, and the difference of thethree groups are significant (χ2=16.732,P <0.05, χ2=15.038,P <0.05, χ2=34.125,P <0.05).Conclusion:The loss expression of LKB1is closely related to theoccurrence, development of endometrial cancer. And detecting the expressionof LKB1in endometrial adenocarcinoma is help to diagnose early.