In Vitro and In Vivo Study on the Effect of Lysosome-associated Protein Transmembrane 4 Beta on the Progression of Breast Cancer / 한국유방암학회지

PURPOSE: Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. METHODS: We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. RESULTS: Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. CONCLUSION: LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment.

Gene mutation and prognosis of extragastrointestinal stromal tumor / 中华普通外科杂志

Objective To evaluate prognostic significance of c-kit and PDGFR-α gene mutation in extragastrointestinal stromal tumors(EGIST). Methods Paraffin embedded tissue specimens from 23 EGISTs were tested for CD117,CD34 and Ki-67 expression by immunohistochemical method.EGIST cases were also tested for the presence of c-kit exons 9,11,13,17 mutations and PDGFR-α exons 12,18 mutations.Kaplan-meier survival rate was used to evaluate the prognostic factors. Results Of 23 cases of EGIST,23(100%)were positive for CD117,17(74%)were positive for CD34.For Ki-67 labeling index(Ki-67 LI):30%were＜1%,44%were between 1%-5%,26%were＞5%.C-kit mutations were detected in 44% of EGIST patients and all were of exon 11 mutations.PDGFR-α mutations were found in 13%of all the 23 cases and all were of exon 18 mutations(The commonest type of mutation D842V).Survival analysis indicated that mitotic count and Ki-67 index were significant predictors for survival.Conclusion The pattern of c-kit and PDGFR-α mutation in EGIST was essentially similar to that in GIST.But the mutation frequency of PDGFR-α was slightly higher in EGIST than in GIST.EGIST could be a special subtype of GIST.The results of this study also show combination of mitotic counts and Ki-67 labeling index may be useful for predicting the prognosis of EGIST.

Comprehensive analysis of factors that involve in survival and prognosis in patients with gastrointestinal stromal tumors / 中华消化杂志

Objective To investigate the survival and prognostic factors in patients with gastrointestinal stromal tumors(GIST).Methods The histopathological slides from 153 patients with GIST were reviewed. The expression of CDllT,CD34,platelet-derived growth factor receptor alpha (PDGFR-a) and Ki-67 proteins were measured by immunohistochemical staining. The factors thatinvolved in the survival and prognosis were analyzed based on the clinical features and GIST biological behavior ranking.The Kaplan-Meier and Cox model were used to evaluate the effect of variant factors on survival and prognosis.Results The survival rate of 135 patients was 94.1% 76.3% and 65.9% at 1,3 and 5 years,respectively.On univariate analysis survival was predicted by tumor size (χ2= 40.565,P＜0.01),primary tumor location (χ2=13.245,P＜0.01),mitotic count (χ2= 22.626,P＜0.01),risk ranking (χ2=19.186,P＜0.01),necrosis (χ2==28.665,P＜0.01),incomplete resection χ2=2 =29.110,P＜0.01) and Ki-67 index (χ2=15.953,P＜0.01).Multivariate analysis demonstrated that thetumor size ＞ 10 cm,primary tumor location,mitotic count＞ 10/50 HPF,high risk subgroup,tumor necrosis and Ki 67 index ＞ 5 % were poor predictors of survival.Ki-67,tumor size and mitotic count were strong poor predictors of survival.Conclusions Fletcher's biological behavior ranking is a good approach to predict prognosis of GIST patients and has significant clinical value.It's better to combine itwith other factors such as Ki-67 index and primary tumor location in order to provide evidence for therapy.