Mao Tsui-Lien, Hsu Chih-Yi, Yen May J, Gilks Blake, Sheu Jim Jinn-Chyuan, Gabrielson Edward, Vang Russell, Cope Leslie, Kurman Robert J, Wang Tian-Li, Shih Ie-Ming
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Hum Pathol. 2006 Sep;37(9):1169-75. doi: 10.1016/j.humpath.2006.04.008. Epub 2006 Jul 7.
Rsf-1 protein is a member of a chromatin-remodeling complex that plays an important role in regulating gene expression and cell proliferation. Our previous study showed that Rsf-1 was an amplified gene that participated in the development of ovarian serous carcinoma. To further elucidate the role of Rsf-1 in ovarian cancer, we studied Rsf-1 immunoreactivity in 294 ovarian tumors of various histologic types. Because the Rsf-1 amplicon overlaps an amplified region reported in breast cancer, we included 782 neoplastic and normal breast tissues for comparison. Immunohistochemistry was performed on tissue microarrays using a 4-tiered scoring system. Overexpression of Rsf-1 was defined as a nuclear immunointensity of 3+ to 4+ because of a strong correlation between 3+ and 4+ immunointensity and Rsf-1 gene amplification, based on our previous fluorescence in situ hybridization analysis. Rsf-1 overexpression was observed in 25% of high-grade ovarian serous carcinomas and in only rare cases (<7%) of low-grade ovarian serous, ovarian endometrioid, and invasive breast carcinomas but not in any ovarian serous borderline tumors, ovarian clear cell carcinomas, ovarian mucinous carcinomas, intraductal carcinomas of the breast, and normal ovaries and breast tissues. Thus, overexpression of Rsf-1 was significantly associated with high-grade ovarian serous carcinoma (P < .05), as compared with other types of ovarian tumors and breast carcinomas. Our results provide evidence that Rsf-1 expression is primarily confined to high-grade serous carcinoma, the most aggressive ovarian cancer. Because Rsf-1 overexpression occurs in only a small number of breast carcinomas, it is unlikely that Rsf-1 is a critical gene in the development of breast carcinoma.
Rsf-1蛋白是一种染色质重塑复合体的成员,在调节基因表达和细胞增殖中发挥重要作用。我们之前的研究表明,Rsf-1是一个参与卵巢浆液性癌发生发展的扩增基因。为了进一步阐明Rsf-1在卵巢癌中的作用,我们研究了294例不同组织学类型的卵巢肿瘤中Rsf-1的免疫反应性。由于Rsf-1扩增子与乳腺癌中报道的一个扩增区域重叠,我们纳入了782例肿瘤性和正常乳腺组织进行比较。使用四级评分系统对组织芯片进行免疫组织化学检测。由于基于我们之前的荧光原位杂交分析,3+和4+免疫强度与Rsf-1基因扩增之间存在强相关性,因此Rsf-1的过表达被定义为核免疫强度为3+至4+。在25%的高级别卵巢浆液性癌中观察到Rsf-1过表达,而在低级别卵巢浆液性癌、卵巢子宫内膜样癌和浸润性乳腺癌中仅在罕见病例(<7%)中观察到,在任何卵巢浆液性交界性肿瘤、卵巢透明细胞癌、卵巢黏液性癌、乳腺导管内癌以及正常卵巢和乳腺组织中均未观察到。因此,与其他类型的卵巢肿瘤和乳腺癌相比,Rsf-1过表达与高级别卵巢浆液性癌显著相关(P < 0.05)。我们的结果提供了证据表明,Rsf-1表达主要局限于高级别浆液性癌,即最具侵袭性的卵巢癌。由于Rsf-1过表达仅在少数乳腺癌中出现,因此Rsf-1不太可能是乳腺癌发生发展中的关键基因。