Mao Y N, Zeng L X, Li Y H, Liu Y Z, Wu J Y, Li L, Wang Q
Laboratory of Early Prevention and Treatment for Regional High Frequence Tumor Ministry of Education Key Laboratory, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
Zhonghua Fu Chan Ke Za Zhi. 2017 Oct 25;52(10):687-696. doi: 10.3760/cma.j.issn.0529-567X.2017.10.008.
To explore the origin of ovarian high grade serous carcinoma (HGSC) through analysing the expression and significance of PAX8, PAX2, p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma) and 5 non-epithelial ovarian cancer (sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer, there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray. (1) To analyze the expression and differences of PAX8, PAX2, p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods. (2) To compare the expression levels of PAX8, PAX2, p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8, PAX2, p53 and RAS expression of HGSC. (4) To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. (1) PAX8, PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group, but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete cells of normal fallopian tube epithelium. (2) p53 and RAS expression of fallopian tube epithelium in the epithelial ovarian cancer group were significantly higher than those in the non-epithelial ovarian cancer groups (0.05), but the expression of PAX8 and PAX2 in fallopian tube and the expression of PAX8, PAX2, p53 and RAS in ovarian tissue was not statistically significant in the groups (0.05). PAX8, PAX2 and p53 expression of the ovarian in HGSC group were significantly higher than those in LGSC group (0.05), while the expression of RAS was lower in the ovarian of the high-grade group (0.05), while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not statistically significant in the groups (0.05). (3) There was a significantly positive correlation between fallopian tube and the corresponding ovary of HGSC in PAX8 and PAX2 expression (0.422, 0.045; 0.693, 0.000), but not correlation in p53 and RAS expression (0.058, 0.793; 0.190, 0.384). (4) Univariate survival analysis showed that the progression free survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8, PAX2 and RAS (0.05), but there were not correlated with age, surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and p53 protein expression (0.05). The total survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8 (0.05), but there were not correlated with age,surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and the protein expression of PAX2, RAS and p53 (0.05). PAX8, PAX2, p53, RAS are of great significance for the study of origin of HGSC. HGSC may be derived from fallopian tube, but further investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be expected to be used as predictors of survival prognosis in patients with ovarian serous cancer.
通过分析PAX8、PAX2、p53和RAS在不同类型和分级的浆液性癌的卵巢及输卵管中的表达及意义,探讨卵巢高级别浆液性癌(HGSC)的起源。2015年1月至2016年1月,从广西医科大学附属肿瘤医院收治的患者中收集了44例卵巢肿瘤组织样本,其中包括34例恶性卵巢肿瘤和10例正常组织(作为对照组)。输卵管组织按伞端、壶腹部、峡部分段,相应的卵巢组织取同侧。34例卵巢癌患者中,包括29例上皮性卵巢癌(27例浆液性癌、1例黏液性癌、1例子宫内膜样腺癌)和5例非上皮性卵巢癌(性索间质肿瘤)。27例卵巢浆液性癌患者中,有23例HGSC和4例低级别卵巢浆液性癌(LGSC)。山东大学齐鲁医院2005年至2013年诊断为卵巢浆液性癌的153例样本制作了组织芯片。(1)采用免疫组织化学方法分析上述HGSC患者及对照女性的卵巢和输卵管组织及组织芯片中PAX8、PAX2、p53和RAS的表达及差异。(2)比较不同病理类型卵巢癌患者卵巢和输卵管中PAX8、PAX2、p53和RAS的表达水平。(3)分析HGSC中输卵管和卵巢组织PAX8、PAX2、p53和RAS表达的相关性。(4)采用单因素分析方法分析组织芯片中卵巢浆液性癌预后的因素。(1)对照组正常卵巢上皮中PAX8、PAX2、p53和RAS表达为阴性,但正常输卵管上皮分泌细胞中PAX8、PAX2、p53和RAS表达呈强阳性棕色。(2)上皮性卵巢癌组输卵管上皮中p53和RAS表达明显高于非上皮性卵巢癌组(P<0.05),但输卵管中PAX八和PAX2的表达以及卵巢组织中PAX8、PAX2、p53和RAS的表达在两组间差异无统计学意义(P>0.05)。HGSC组卵巢中PAX8、PAX2和p53表达明显高于LGSC组(P<0.05),而高级别组卵巢中RAS表达较低(P<0.05),但输卵管中PAX8、PAX2、p53和RAS的表达在两组间差异无统计学意义(P>0.05)。(3)HGSC中输卵管与相应卵巢PAX8和PAX2表达呈显著正相关(r=0.422,P=0.045;r=0.693,P=0.000),但p53和RAS表达无相关性(r=0.058,P=0.793;r=0.190,P=0.384)。(4)单因素生存分析显示,卵巢浆液性癌组患者的无进展生存时间与PAX8、PAX2和RAS蛋白表达显著相关(P<0.05),但与年龄、手术分期、细胞分化、淋巴结转移及术前化疗和p53蛋白表达无关(P>0.05)。卵巢浆液性癌组患者的总生存时间与PAX8蛋白表达显著相关(P<0.05),但与年龄、手术分期、细胞分化、淋巴结转移及术前化疗和PAX2、RAS和p53蛋白表达无关(P>0.05)。PAX8、PAX2、p53、RAS对HGSC起源的研究具有重要意义。HGSC可能起源于输卵管,但需进一步研究证实。PAX8、PAX2、p53、RAS有望作为卵巢浆液性癌患者生存预后的预测指标。