Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562 Japan.
Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562 Japan.
Hum Pathol. 2019 Apr;86:32-37. doi: 10.1016/j.humpath.2018.11.013. Epub 2018 Nov 26.
Ovarian clear cell carcinomas (CCCs) have 2 distinct stromas: a hyalinized/mucoid stroma and a plasma cell-rich inflammatory stroma. Clinically, CCC is the most common ovarian cancer associated with thromboembolism. Recent studies suggested a potential role of PIK3CA mutation in the cyclooxygenase (COX) pathway, which mediates inflammation or hemostasis. In the present study, 54 ovarian CCCs and 3 CCC cell lines were analyzed for PIK3CA hotspot mutation and COX-2 expression with special reference to stromal features. Among the 54 CCCs, 20 (37.0%) and 8 (14.8%) were classified as CCCs with a hyalinized/mucoid stroma and an inflammatory stroma, respectively. PIK3CA mutation was identified in 11 (55%) of the 20 CCCs with a hyalinized/mucoid stroma, but not in any of the 8 CCCs with an inflammatory stroma. In contrast, COX-2 expression was frequent in CCCs with an inflammatory stroma (1/20 [5%] versus 7/8 [87.5%], respectively). Such a relationship between the PIK3CA mutation, COX-2 expression, and stromal features was repeated in the 3 CCC cell lines. Thromboembolism was noted in 9 (16.7%) of the 54 CCC patients, and it was more frequent in CCCs with a hyalinized/mucoid stroma (7/20 [35%]) than in those with an inflammatory stroma (0/8 [0%]). In conclusion, there is a difference in PIK3CA mutation, COX-2 expression, and paraneoplastic thromboembolism between CCCs with a different stroma. It is suggested that a different stromal feature, either hyalinized/mucoid change or inflammation, represents a different molecular genetic background or hemostatic potential in ovarian CCCs.
卵巢透明细胞癌 (CCC) 有 2 种不同的基质：玻璃样/黏液样基质和富含浆细胞的炎症性基质。临床上，CCC 是最常见的与血栓栓塞相关的卵巢癌。最近的研究表明，PIK3CA 突变在环氧化酶 (COX) 途径中可能发挥作用，该途径介导炎症或止血。在本研究中，分析了 54 例卵巢 CCC 和 3 例 CCC 细胞系的 PIK3CA 热点突变和 COX-2 表达情况，并特别关注了基质特征。在 54 例 CCC 中，20 例（37.0%）和 8 例（14.8%）分别归类为具有玻璃样/黏液样基质和炎症性基质的 CCC。在 20 例具有玻璃样/黏液样基质的 CCC 中，有 11 例（55%）发现 PIK3CA 突变，但在 8 例具有炎症性基质的 CCC 中均未发现。相比之下，具有炎症性基质的 CCC 中 COX-2 表达较为常见（分别为 1/20 [5%]和 7/8 [87.5%]）。这种 PIK3CA 突变、COX-2 表达与基质特征之间的关系在 3 例 CCC 细胞系中得到了重复。在 54 例 CCC 患者中，有 9 例（16.7%）发生血栓栓塞，其中具有玻璃样/黏液样基质的 CCC 中更常见（7/20 [35%]），而具有炎症性基质的 CCC 中则罕见（0/8 [0%]）。总之，不同基质的 CCC 之间在 PIK3CA 突变、COX-2 表达和副瘤性血栓栓塞方面存在差异。提示卵巢 CCC 中不同的基质特征，无论是玻璃样/黏液样改变还是炎症，代表了不同的分子遗传学背景或止血潜能。
