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The Clinical And Pathological Features And Prognostic Factors Of Gastric GIST In Patients Over 60 Years Old And Prognostic Affect Of PKC-θ And FAK In Gastric GIST In Patients Over 60 Years Old

Posted on:2016-12-26Degree:MasterType:Thesis
Country:ChinaCandidate:P LiFull Text:PDF
GTID:2284330464951525Subject:General surgery
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Gastric GISTS are tumors that arise from stomach mesenchymal tissue which account for 65%-75% of gastrointestinal stromal tumors, featuring positive expression of CD117(c-Kit) and CD34 protein. Most of the patients are aged between 45 to 70 years old and teenagers are rare. As the improvement of people’s living standard and social medical treatment, aging has become one of important characteristics of the current population. At present, incidence of gastric stromal tumor is surging among the elderly over the age of 60 for multiple organ degradation and several accompanying chronic diseases. Since gastric GIST in the elderly is different in Targeted drug tolerance, postoperative survival rate and choice of operational methods, it is of great medical and social value to explore the clinical and pathologic features and prognosis factors of gastric GIST in the elderly.PKC-θ is a new subtype of PKC which draw much attention in cancer research field in recent years. It is weighted 77-83 kDa and featured by independence of Ca2+ regulation. PKC-θ may be a new GIST diagnostic indicator besides CD117 and DOG-1 which is confirmed by the research of poole, et al. that the accompanied detection of PKC-θ and c-kit protein can significantly increase the sensitivity of gastric GIST diagnosis. However there are no reports about PKC-theta prognostic value in patients with Gastric gastrointestinal stromal tumors at home and abroad.Focal adhesion kinase (FAK) is one of the members in the receptor independent tyrosine kinase family, whose gene is localized on the chromosome 8q24 in human. Existing studies have shown that FAK plays an important role in malignant transformation, recurrence and metastasis in a variety of solid tumors, such as gastric cancer, ovarian cancer and liver cancer. Koon discovered the significantly up-regulated expression of FAK malignant gastric GIST according to the GST gene expression profile using the methods of quantitative real-time PCR. It has started a controversy that whether or not FAK plays an important role in the postoperative recurrence and metastasis.Objectives:To study the clinical features and prognostic factors of gastric GIST in the elderly over 60 years old and the prognostic influence and clinical value of PKC-θ and FAK protein in gastric GIST in the elderly over 60 years old.Data and Ways:The 1st section:132 patients over 60 years with primary gastric GIST who were admitted to PLA general hospital as Jan.2005 to Jan.2015 were backly analyzed. The clinical and pathological data and factors of postoperative status were gathered and analysed by Cox model. Whole measurement data were compared using t test, and the life of patients was compared by the life diagram and Kaplan-Meier survival curves. The 2nd section: 105 people who were permitted to PLA hospital as Jan.2007 to Dec.2013 were backly investigated and fl.up. IHC way was applied to observe the expression of PKC-θ and FAK in GISTs tissues. Chi-square test is applied to compare for all numeration data, and the life of patients was compared by the life diagram and Kaplan-Meier survival curves,Results:The life ratio of 1-year was 97%,3-year was 95%,5-year was 92% in all patients over 60 years old. The prognosis factors of gastric GIST in patients over 60 years old are as follows:Ki-67, CD34, tumor diameter, R0 resection, regularly postoperative targeted therapy, rupture of tumor during surgery, pathological mitotic rates, recurrence and metastasis. They are of significant influence to the survival rates of gastric GIST (P<0.05). The greater of values of influence factors, the higher of the risk of death. The factors like gender, CD 117, location, gastric mucosal erosion, neural and myogetic differentiation and whether accompanied with diabetes, hypertension show no significant influence to the survival rates of gastric GIST (P>0.05). Multi-factor model survival analysis indicated that R0 resection and regularly postoperative targeted therapy were independent factors affecting the survival rates of gastric GIST in patients over 60 years old.In the patients over 60 years old with negative expression of PKC-θ protein, the life ratio of 1-year was 93%,3-year was 87%,5-year was 84% and with positive expression of PKC-θ protein, the survival rates of 1-year,3-year, 5-year were 84%,71% and 50% with statistically significant difference(Log Rank P=0.002). In the patients over 60 years old with positive expression of FAK protein, the survival rates of 1-year,3-year,5-year were 82%,62% and 52% and with negative expression of FAK protein, the survival rates of 1-year,3-year, 5-year were 98%,97% and 95%, with statistically meaningful diversity (Log Rank P=0.000).Conclusions:Surgery is of the priority in the treatment of gastric GIST in patients over 60 years old. R0 resection and regularly postoperative targeted therapy can improve the prognosis and extend survival time. Ki-67, CD34, diameter, R0 resection, regularly postoperative targeted therapy, rupture of tumor during surgery, pathological mitotic rates, recurrence and metastasis are the factors that affect the prognosis of gastric GIST in patients over 60 years old, which benefits the standardized therapy of gastric GIST. PKC-θ and FAK are important clinical indicators of tumor malignancy, recurrence and metastasis. And postoperative PKC-θ and FAK targeted therapy may become one of new treatment methods in gastric GIST therapy.
Keywords/Search Tags:Gastric gastrointestinal stromal tumors, prognosis, therapy, PKC-θ, FAK
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