Prognostic significance of PTEN,Ki-67 and CD44s expression patterns in gastrointestinal stromal tumors

AIM:To develop a prognostic approach for gastrointestinal stromal tumors(GISTs) using a cluster of indicators and follow-up information.METHODS:One hundred and four GISTs that had not been subjected to targeted therapies were collected and classified by NIH risk assessment and anatomic location.By immunohistochemistry,the expressions of PTEN,Ki-67,CD44s matrix metalloproteinase(MMP)-9 and TIMP-1 were detected on tissue microarray.Univariate and multimarker survival analyses were performed and then a COX hazard proportion model was constructed to evaluate a cluster of predictors of GIST.RESULTS:Our data showed small intestinal GIST are more aggressive than gastric GIST.The NIH risk assessment correlated with disease-free survival foreither gastric GIST or small intestinal GIST.Immunohistochemical analysis revealed that Ki-67 labeling indexes(LIs) < 5% predicted higher disease-specific survival(DSS) in gastric and small intestinal GIST.CD44s positivity and PTEN LIs ≥ 50% correlated with higher DSS in gastric GIST.MMP-9 and TIMP-1 had no correlation with survival.Multimarker analysis revealed that the expression pattern of PTEN LIs ≥ 50% combined with Ki-67 LIs < 5% and CD44s positivity reliably predicted favorable outcomes for gastric GIST(P = 0.009),as did the combination of PTEN LIs ≥ 50% and Ki-67 LIs < 5% for small intestinal GIST(P = 0.011).Authors also found that high NIH risk grade was correlated with DSS in patients with gastric GIST and disease-free survival in patients with small intestinal GIST.CONCLUSION:PTEN LIs ≥ 50%,Ki-67 LIs < 5% and CD44s positivity provides an accurate,favorable prognosis for gastric GIST.PTEN LIs ≥ 50% and Ki-67 LIs < 5% does the same for small intestinal GIST.Ki-67 LIs enhances the NIH assessment.

The GIOME:Concept and current role in gastrointestinal tract studies

The goal of the Physiome Project is to understand and describe the physiology and pathophysiology of the human organism. Multiscale mathematical and computer models are developed within this concept to help understand human health. From its beginning about 15 years ago, most of the focus has been in the cardiac field (the Cardiome project) but other areas are developing as well now.

Immunohistochemical Study of Hexose Transporters GLUT-2 and GLUT-5 in Birds Gastrointestinal Tract

The hexoses glucose, galactose and fructose serve as important dietary energy sources in animals and glucose plays a central role in energy homeostasis within eucaryotic cells. As relatively little is known about patterns of hexose transporters expression in birds gastrointestinal tract, the aim of the study was to examine glucose transporters 2 （GLUT-2） and glucose transporters 5 （GLUT-5） expression in stomach and duodenal epithelium of two different species--broilers （Gallus gallus domesticus） and ostriches （Struthio camelus var. domesticus） chicken. Materials from the two parts of gastrointestinal tract were collected from six 7-day-old female broilers and six 7-day-old female ostriches. Specimens were fixed with 10% formalin, embedded into paraffin, cut into 7 lain thick slices, followed by immunohistochemical staining with polyclonal primary antibodies rabbit anti-GLUT-2 and rabbit anti-GLUT-5; the staining was carried out according to the manufacturers guidelines （IHC kit, Abcam, UK）. The investigation showed that the staining for both antibodies was more intensive in the epithelial cells of stomach and duodenum of the 7-day-old broilers. In duodenal epithelium, goblet cells and brush border membranes were stained in both species, however the signal was stronger for GLUT-5 than GLUT-2. Staining for GLUT-2 and GLUT-5 occurred in different parts of gastrointestinal tract of 7-day-old ostriches, but was weaker compared to 7-day-old broilers, which showed that the gastrointestinal tract of 7-day-old female broilers was more developed for transportation ofhexoses than 7-day-old female ostriches.

Prognostic Factors of Gastrointestinal Stromal Tumors： A Single Institutional Retrospective Experience with Surgical Management over 20 Years

OBJECTIVE To analyze the pathological features and prognosis factors of gastrointestinal stromal tumor （GIST） after primary resection. METHODS Medical records of the diagnosis, surgery, and follow-up of 327 patients with GISTs who underwent surgery between 1988 and 2007 were retrospectively reviewed. The predic-tive factors for the survival of these patients were identi. ed using multivariate analysis. RESULTS In the 327 tumors, 152 （46.5%） were located in the stomach, 89 （27.2%） in the small intestine, 33 （10.1%） in the colon and rectum, and 43 （13.1%） in other sites including the omentum and mesentery. The 3-year and 5-year overall survival rates of the 327 GIST patients were 74.4% and 62.7%, respectively, and univariate survival analysis demonstrated that factors, such as tumor size, mitotic index, NIH categories, Ki-67 index, tumor location, surgical margins, tumor bleeding, and tumor necrosis have significant effect on survival of the patients （P 〈 0.05）. Multivariate analysis demonstrated that the NIH categories, surgical margins, and Ki-67 index were independent prognostic factors for the survival rate. In the group of patients with postoperative recurrence or metastasis, the median survival time of patients who did not receive imatinib treatment was 30 months and that of patients who received imatinib treatment was 59 months. Their 5-year survival rates were 16.4% and 39.4%, respectively, and the difference was statistically significant （P = 0.017）. CONCLUSION Complete resection is the .rst choice of treat-ment for GISTs. It is reasonable to evaluate the prognosis of resect-able GISTs and guide the adjunctive therapy with NIH categories and Ki-67 index. Imatinib treatment can signi.cantly increase the survival rate of patients with recurrent and metastatic GISTs.