Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada.
Int J Gynecol Pathol. 2011 Jul;30(4):366-71. doi: 10.1097/PGP.0b013e31820d20ba.
Neoadjuvant therapy has an emerging role in the treatment of high-stage ovarian carcinoma. Some ovarian carcinoma subtypes do not respond well to standard chemotherapy, making accurate subtype diagnosis before starting therapy important. This diagnosis is frequently based on omental biopsy specimens. In particular, with very small biopsies, immunostaining for diagnostic biomarkers may be needed. To assess intratumoral heterogeneity of biomarker expression in pelvic high-grade serous carcinoma, we compared the expression of a set of 10 biomarkers between ovarian and omental sites. Tissue microarrays were constructed from 123 high-grade serous carcinomas with paired ovarian and omental tumor samples. These samples were stained with biomarkers that have been used in ovarian carcinoma subtype diagnosis (WT1, TP53/p53, MUC16/CA125, CDKN2A/p16), and with biomarkers of the tumor microenvironment (CD8, CD163, SPARC, PDGFRB), cell adhesion (CDH1/E-Cadherin), and proliferation (Ki67) as well. Expression frequencies in samples from the 2 sites were compared, as was concordance at the 2 sites for individual tumors. The 2 markers of desmoplastic stromal response (PDGFRB, SPARC) were more frequently expressed in the omentum compared with the ovary (P<0.001; McNemar test). The other 8 markers did not show a significant difference in the frequency of expression between sites. Within individual cases, some markers such as Ki67 and CDKN2A showed variability, indicating that these markers are affected by intratumoral heterogeneity. The intratumoral variability for MUC16, TP53, and WT1 was modest. Commonly used diagnostic markers, such as TP53 and WT1, show little variability between ovarian and omental sites, suggesting that they can be successfully used in small biopsy specimens from extraovarian sites. In contrast, markers of host stromal response do vary between sites, suggesting a biologic difference of the microenvironment at different sites that should be taken into account when tissue-based research is carried out.
新辅助疗法在治疗晚期卵巢癌中具有重要作用。某些卵巢癌亚型对标准化疗反应不佳，因此在开始治疗前准确诊断亚型非常重要。这种诊断通常基于大网膜活检标本。特别是对于非常小的活检标本，可能需要进行诊断生物标志物的免疫染色。为了评估盆腔高级别浆液性癌中生物标志物表达的肿瘤内异质性，我们比较了卵巢和大网膜部位的一组 10 种生物标志物的表达。从 123 例具有配对卵巢和大网膜肿瘤样本的高级别浆液性癌中构建组织微阵列。这些样本用用于卵巢癌亚型诊断的生物标志物（WT1、TP53/p53、MUC16/CA125、CDKN2A/p16）以及肿瘤微环境的生物标志物（CD8、CD163、SPARC、PDGFRB）、细胞黏附（CDH1/E-钙黏蛋白）和增殖（Ki67）进行染色。比较了 2 个部位样本的表达频率，并比较了 2 个部位的肿瘤个体一致性。与卵巢相比，2 种促纤维组织反应的标志物（PDGFRB、SPARC）在大网膜中表达更为频繁（P<0.001；McNemar 检验）。其他 8 个标志物在部位之间的表达频率没有显著差异。在个体病例中，一些标志物，如 Ki67 和 CDKN2A，表现出可变性，表明这些标志物受到肿瘤内异质性的影响。MUC16、TP53 和 WT1 的肿瘤内变异性适中。常用的诊断标志物，如 TP53 和 WT1，在卵巢和大网膜部位之间变化不大，这表明它们可以成功用于卵巢外部位的小活检标本。相比之下，宿主基质反应的标志物在部位之间确实存在差异，这表明不同部位的微环境存在生物学差异，在进行基于组织的研究时应考虑到这一点。
