Kieback D G, McCamant S K, Press M F, Atkinson E N, Gallager H S, Edwards C L, Hajek R A, Jones L A
Experimental Gynecology/Endocrinology Laboratory, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1993 Nov 1;53(21):5188-92.
Conventional cytosol estrogen receptor analysis is not a significant prognostic variable in serous ovarian carcinoma. Although the use of immunocytochemical receptor analysis for estrogen does provide prognostically useful information in enhanced accuracy of predicting survival in patients with ovarian cancer, its usefulness can still be improved. Surgical samples from ovarian carcinomas are heterogeneous in tissue composition. Immunocytochemical receptor analysis allows for the specific assessment of the tumorous portions of a histological specimen. However, it is limited by its dependence on staining intensity as the determining factor. Biochemical receptor analysis does provide objective information concerning the number of receptor molecules present in a given sample, but the value is not adjusted for histological composition of the tumor section. Therefore, we have attempted to combine the advantages of both methods. By adjusting the conventional receptor analysis for the percentage of tumor present in the specimen, we have eliminated the tissue heterogeneity as a confounding variable. The resulting value is named Composition Adjusted Receptor Level or CARL. A prospective study was performed on the estrogen receptor concentrations in 61 ovarian cancers. Minimum follow-up was 8 years. For the percentage of tumor in the specimen, a highly significant correlation of the assessment of the two pathologists was observed. Stage (P < 0.05) and grade (P < 0.05) as well as cell type (P < 0.05) were found to be significant prognostic variables. In an attempt to eliminate the confounding influences of these variables, the CARL of the estrogen receptor was assessed with regard to its prognostic significance in 32 grade 2 and 3 serous carcinomas of the ovary, stage III and IV. A linear correlation between CARL and survival was found above a threshold estrogen receptor concentration of 15 fmol/mg cytosol protein using a correlation of the Cox proportional hazards model (P < 0.02). Our data suggest that (a) the assessment of the percentage of tumor in a given sample is not significantly observer dependent, (b) CARL is a significant predictor of survival in serous ovarian carcinoma, and (c) a CARL should be determined for the analysis of any cytosol receptor in solid tumors.
传统的胞质雌激素受体分析在浆液性卵巢癌中并非重要的预后变量。尽管使用雌激素免疫细胞化学受体分析确实能在提高预测卵巢癌患者生存率准确性方面提供具有预后价值的信息，但其效用仍可进一步提升。卵巢癌手术样本的组织成分具有异质性。免疫细胞化学受体分析能够对组织学标本中的肿瘤部分进行特异性评估。然而，它受限于将染色强度作为决定因素。生化受体分析确实能提供有关给定样本中存在受体分子数量的客观信息，但该数值未针对肿瘤切片的组织学组成进行调整。因此我们尝试结合两种方法的优势。通过针对标本中肿瘤的百分比对传统受体分析进行调整，我们消除了组织异质性这一混杂变量。所得数值被命名为成分调整受体水平（CARL）。我们对61例卵巢癌的雌激素受体浓度进行了一项前瞻性研究。最短随访时间为8年。对于标本中肿瘤的百分比，观察到两位病理学家的评估具有高度显著的相关性。发现分期（P <0.05）、分级（P <0.05）以及细胞类型（P <0.05）均为显著的预后变量因素之一。为了消除这些变量因素的混杂影响，我们在32例III期和IV期2级和3级浆液性卵巢癌中评估了雌激素受体的CARL及其预后意义。使用Cox比例风险模型相关性分析发现，当雌激素受体浓度阈值高于15 fmol/mg胞质蛋白时，CARL与生存率之间存在线性相关性（P <0.02）。我们的数据表明：（a）对给定样本中肿瘤百分比进行评估时观察者依赖性不显著；（b）CARL是浆液性卵巢癌生存的显著预测指标；（c）对于实体瘤中任何胞质受体的分析都应确定CARL。
