Tringler Barbara, Liu Wenhui, Corral Laura, Torkko Kathleen C, Enomoto Takayuki, Davidson Susan, Lucia M Scott, Heinz David E, Papkoff Jackie, Shroyer Kenneth R
Department of Pathology, University of Colorado Health Sciences Center, B-216, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Gynecol Oncol. 2006 Jan;100(1):44-52. doi: 10.1016/j.ygyno.2005.08.060. Epub 2005 Oct 26.
Despite great advances in therapeutic management, the mortality rate for ovarian cancer has remained relatively stable over the past 50 years. This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary.
Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. Univariate analyses were used to test for statistically significant relationships.
B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (n = 12), and clear cell carcinomas (n = 15), and in all metastatic serous (n = 23) and endometrioid (n = 7) ovarian carcinomas. By contrast, focal B7-H4 expression was detected in only 1/11 mucinous carcinomas. The proportion of positive cells and median staining intensity was greater in serous carcinomas than in serous cystadenomas or serous tumors of low malignant potential, and the differences were statistically significant (P < 0.0001 and P = 0.034, respectively). The median staining intensity was also significantly greater in endometrioid carcinomas than in endometriosis (P = 0.005).
The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer.
尽管在治疗管理方面取得了巨大进展，但在过去50年中，卵巢癌的死亡率一直相对稳定。本研究旨在通过定量PCR分析，评估最近被确定为乳腺癌和卵巢癌潜在分子标志物的B7-H4蛋白在卵巢良性肿瘤、低恶性潜能肿瘤和恶性肿瘤中的表达情况。
采用免疫组织化学方法，对浆液性、黏液性、子宫内膜样和透明细胞卵巢肿瘤的存档福尔马林固定组织块进行评估，以检测B7-H4表达的分布情况，并通过自动图像分析测量染色强度。采用单因素分析来检验统计学上的显著关系。
在所有原发性浆液性癌（n = 32）、子宫内膜样癌（n = 12）和透明细胞癌（n = 15），以及所有转移性浆液性癌（n = 23）和子宫内膜样癌（n = 7）中均检测到B7-H4的细胞质和膜表达。相比之下，仅在1/11的黏液性癌中检测到局灶性B7-H4表达。浆液性癌中阳性细胞比例和中位染色强度高于浆液性囊腺瘤或低恶性潜能的浆液性肿瘤，差异具有统计学意义（分别为P < 0.0001和P = 0.034）。子宫内膜样癌的中位染色强度也显著高于子宫内膜异位症（P = 0.005）。
B7-H4在浆液性、子宫内膜样和透明细胞卵巢癌中持续过表达，而在大多数正常体细胞组织中相对缺乏表达，这表明B7-H4应作为卵巢癌的潜在诊断标志物或治疗靶点进行进一步研究。
