Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density.
OBJECTIVE
Angiogenesis, estimated by microvessel density (MVD), has been shown to predict poor progression-free survival in women with advanced epithelial ovarian cancer. Inhibitor of growth (ING) family proteins inhibit angiogenesis in a number of cancers. We evaluated the role of ING4 in regulation of angiogenesis in patients with epithelial ovarian cancer.


METHODS
Semi-quantitative RT-PCR was used to determine ING4 mRNA levels in 40 ovarian cancer patients and 40 normal controls. Also, we used immunohistochemistry to evaluate (1) ING4 protein expression levels and (2) the level of MVD by staining CD34, a microvessel marker, in these patients. Through statistical analysis, the possible correlation between the ING4 expression and angiogenesis was explored.


RESULTS
ING4 mRNA and protein were significantly downregulated in all ovarian cancer patients compared to normal controls (P < 0.001). Endometrioid carcinoma tissue had significantly lower ING4 levels compared to serous or mucinous ovarian cancer. ING4 expression correlated negatively with stage and histological grade of ovarian cancers. MVD correlated negatively with ING4 protein and mRNA levels (ρ = -0.865; P < 0.001 and ρ = -0.724; P < 0.001, respectively).


CONCLUSIONS
Loss of ING4 may promote microvessel formation and plays a role in facilitating the development of ovarian cancer. Although the specific mechanisms are not yet understood, our data suggest that ING4 may be a promising target for the treatment for ovarian cancer.
Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Yinglan
Y
Liu
Liqian
L
Yu
Yingwei
Y
Wang
Yaling
Y
Zhang
Yingchao
Y
Wang
Guangmei
G
Zhang
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D055806:Microvessels / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D018952:Antigens, CD34; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D025521:Tumor Suppressor Proteins