Zhu Qin, Qu Yuqing, Zhang Qiongyan, Lu Linghui, Weng Weiwei, Zhang Hao, Zhang Lihong, Ning Yan, Wang Yiqin
Department of Pathology, Obstetrics and Gynecology Hospital of Fudan UniversityNo. 419, Fang-xie Road, Shanghai 200011, China.
Department of Pathology, Fudan University Shanghai Cancer CenterShanghai 200032, China.
Am J Transl Res. 2017 Jul 15;9(7):3387-3398. eCollection 2017.
Primary ovarian mucinous tumors progress from benign adenoma to borderline tumors to invasive mucinous carcinoma. A proper differential diagnosis is crucial to discriminate malignancies at the early stages of disease. However, few biomarkers are clinically available. We designed this study to analyze the clinical application of the oncogene IMP3 in monitoring early malignancies in ovarian primary mucinous tumors.
We collected 250 samples of ovarian primary mucinous tumors along with the corresponding clinicopathological information between 2009 and 2015 at the Gynecology and Obstetrics Hospital of Fudan University and performed immunochemical assays. Statistical analysis of the correlation between expression of IMP3 and clinic-pathological parameters as well as the survivals of these patients was carried out. Finally, wound-healing and transwell assays were performed in SKOV3 and CAOV3 cells.
The expression rate and intensity of IMP3 were much higher in invasive carcinoma than those in benign adenoma and classic borderline adenoma (<0.05). The expression rate and intensity of IMP3 were also higher in cases with mucinous intraepithelial carcinoma than those in cases with classic borderline tumors (<0.05). Among the malignant cases, the expression rate and intensity of IMP3 increased with advancing FIGO staging (<0.05). The expression rate and intensity of IMP3 were much higher in cases with involved fallopian tubes, uterine and omentum than those in cases without the involvement of these tissues (<0.05). The expression rate and intensity of IMP3 were much higher in cases with lymph node metastasis than those in cases without lymph node metastasis (<0.05). Elevated expression of IMP3 significantly deteriorated the disease-free survival (DFS) and overall survival (OS) of mucinous carcinoma (<0.05). IMP3 was an independent risk factor of DFS but not OS. Further experiments indicated that IMP3 promoted the proliferation, motility and invasive potential of ovarian tumor cells.
IMP3 is highly expressed in ovarian mucinous tumors and is positively correlated with malignancy. IMP3 could be used in the differential diagnosis of ovarian mucinous tumors and might be applicable in monitoring tumor initiation and progression.
原发性卵巢黏液性肿瘤可从良性腺瘤发展为交界性肿瘤，再进展为浸润性黏液癌。准确的鉴别诊断对于在疾病早期区分恶性肿瘤至关重要。然而，临床上可用的生物标志物很少。我们设计了本研究，以分析癌基因IMP3在监测卵巢原发性黏液性肿瘤早期恶性病变中的临床应用。
2009年至2015年期间，我们在复旦大学附属妇产科医院收集了250例卵巢原发性黏液性肿瘤样本及相应的临床病理信息，并进行了免疫化学分析。对IMP3表达与临床病理参数以及这些患者生存率之间的相关性进行了统计分析。最后，在SKOV3和CAOV3细胞中进行了伤口愈合和Transwell实验。
IMP3在浸润性癌中的表达率和强度远高于良性腺瘤和经典交界性腺瘤（<0.05）。IMP3在黏液上皮内癌病例中的表达率和强度也高于经典交界性肿瘤病例（<0.05）。在恶性病例中，IMP3的表达率和强度随着国际妇产科联盟（FIGO）分期的进展而增加（<0.05）。IMP3在输卵管、子宫和网膜受累的病例中的表达率和强度远高于未累及这些组织的病例（<0.05）。IMP3在有淋巴结转移的病例中的表达率和强度远高于无淋巴结转移的病例（<0.05）。IMP3表达升高显著降低了黏液癌的无病生存期（DFS）和总生存期（OS）（<0.05）。IMP3是DFS的独立危险因素，但不是OS的独立危险因素。进一步的实验表明，IMP3促进了卵巢肿瘤细胞的增殖、运动和侵袭能力。
IMP3在卵巢黏液性肿瘤中高表达，与恶性程度呈正相关。IMP3可用于卵巢黏液性肿瘤的鉴别诊断，并可能适用于监测肿瘤的发生和进展。
