Clinical Significance Of DOG1.1Protein Expression In Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumor(GIST) is the most common mesenchymal tumorof the gastrointestinal tract，which originates from the interstitial Cells of Cajal (ICC).In1983, Mazur and Clark firstly named this kind of tumor as “gastrointestinal stromaltumors”. But for a long time, it was often difficult to identify the GIST from thegastrointestinal mesenchymal tumor(GIMT).The current viewpoint of the pathogenesis of the GIST is due to C-Kit (tyrosinekinase receptor) gene or PDGFR α (Platelet-Derived Growth Factor Receptor) genemutations which result in the tyrosine kinase receptor in the cell membrane forcontinual activation, phosphorylation, and then, cause cell proliferation out of controland apoptosis inhibition. CD117and CD34have been taken as the routine clinicalimmunohistochemical test, cause both of which have been regarded as the GISTs’features. But there are still some difference in the guidelines of the GISTinternationally, some suspicious GIST are still difficult to diagnose. Some studiesfound that up to10%of GIST’ CD117staining was negative. At the same time,CD117and CD34positive staining not only expressed in GIST, but also could find inmelanoma, ewing’s sarcoma, fibroedenoma, epithelioid sarcoma and so on.Furthermore, molecular biological chemical test is expensive, it also requires highly in the laboratory and the technicians, which limits its application.It has been urgent for us to diagnose gastrointestinal stromal tumor accurately inthe research and clinic, since targeted therapy with imatinib for gastrointestinalstromal tumor put forward in2000years later.DOG1protein is encoded by the DOG1gene which located in the11qchromosome. Several researches had published that DOG1protein expressed highlyin GIST since2004, but researches were still few in domestic.This research was to study the clinical features and the expression of the DOG1.1protein in the GIST. Explored the diagnostic value of the various auxiliaryexaminations, especially the immunohistochemical markers, also discussed somefactors which may affect the GISTs’ prognosis, so as to accumulate more clinicalmaterials, guide the diagnosis and treatment of this disease.【Objective】To investigate the clinical pathological data of GIST retrospectiely, especiallydetect the expression of DOG1.1protein in GIST, and compare it with the CD117andCD34, to discuss the clinical significance of DOG1.1in GIST.【Methods】1. Collected the GIMTs which had been diagnosed by immunohis-tochemistry(IHC) from January2006to April2011through the third affiliatedhospital of Sun Yat-sen University’s electronic medical records systems.2. Collected the GIMTs’ clinical data, including: Diagnosis; Tumor primary sites;Clinical complaints, Signs; Auxiliary examination: blood conventional test, stoolconventional test, liver function, Kidney function，serum tumor markers (CEA, AFP,CA199, CA125etc.); Treatment; Survival ends; B ultrasound, Computed tomography(CT), gastroscope, colonoscopy, ultrasound endoscope for the diagnosis of the GISTs.3. Collected the GIMTs’ pathological features, including: gross morphology, HEstaining microscopically morphology, mitotic activity, NIH risk category,immunohistochemical stainings: CD117, CD34, SMA, Des, S-100, and so on.4. Detected the expression of DOG1.1protein in the GIMTs by IHC. 【Results】1. Eighty-seven GIMTs were diagnosed between January2006and April2011.Of these there were69GISTs,10leiomyomas,3leiomyosarcomas,1melanoma and4schwannomas.2. Among GISTs,38cases were male,31ceses were female, male to female ratiowas1.2/1. The age ranged from29years to87years with a mean age of59.0. Theincidence locations were: stomach (n=33,47.8%), duodenum (n=6,8.7%), smallintestinal (n=16,23.2%), colon (n=2,2.9%) and the extra-gastrointestinal stromaltumors (n=12,17.4%). The most common clinical symptoms were as follows:gastrointestinal bleeding （n=22,31.9%), abdominal pain (n=17,24.6%), andabdominal distention (n=9,13.0%). The diagnosis rate of CT, B ultrasound, ordinaryendoscope(gastroscope or colonoscopy) and endoscopic ultrasound(EUS) is42.6%,22.2%,11.1%,61.1%respectively. The diagnosis rate was statistically differentbetween ordinary endoscope and EUS (P<0.05).3. Among the GIST the positive rates of the DOG1.1, CD117, CD34were91.5%,95.7%,78.3%respectively. Among the non-GIST the positive rates of theDOG1.1, CD117, CD34were0.0%,6.3%,33.3%respectively. There was nosignificant difference between the CD117and DOG1.1positive rate in the GIST (P>0.05), but both of them were higher than CD34(P <0.05). All of the above three IHCmarekers expressed higher in gastrointestinal tract than those out of thegastrointestinal tract (P <0.05). DOG1.1was found to have91.5%sensitivity and100%specificity in diagnosis of GIST, whereas CD117demonstrated95.7%sensitivity and93.8%specificity, and CD34showed78.3%sensitivity and66.7%specificity. DOG1.1was often moderate to strong cell membrane or cytoplasmstaining (83%).4. Single factor survival analysis showed that the GISTs’ prognosis was relevantto the primary tumor location, tumor size, NIH risk classification, DOG1.1stainingresult and treatment (P <0.05). Primary in the EGIST, the bigger, the higher risk,DOG1.1negative and who did not receive surgery were poor predictors of survival. 【Conclusion】GIST was the most common mesenchymal neoplasm of the gastrointestinal tract,often onset in the middle-aged or elderly people. Combine the imaging examination(B ultrasound and CT) and the endoscopy would be helpful to diagnose the GIST.What’s more, endoscopic ultrasound was much better for diagnosing GIST thanordinary endoscope. The positive rates of DOG1.1in GIST was higher than CD34,but similar to CD117. DOG1.1and CD117showed high sensitivity and specificity,could be first indicator for GIST. The primary tumor location, tumor size, riskclassification, DOG1.1staining result and treatment might be significant predictors ofsurvival for the GIST, which need further studies with a larger sample.