Rodríguez-Rodríguez L, Sancho-Torres I, Leakey P, Gibbon D G, Comerci J T, Ludlow J W, Mesonero C
Division of Gynecologic Oncology, University of Rochester, Rochester, New York, 14642, USA.
Gynecol Oncol. 1998 Nov;71(2):223-9. doi: 10.1006/gyno.1998.5108.
CD44 is a surface glycoprotein widely distributed among different tissues. Malignant tumors may show a more complex pattern of CD44 expression, indicating a loss of splice control. The aim of our study is to investigate the expression of CD44 splice variants (CD44v) and its metastatic potential in clear cell carcinoma of the ovary.
Twenty-two cases of clear cell carcinoma of the ovary were evaluated for CD44 standard form (CD44s) and splice variants: -4v, -6v, and -9v expression by immunocytochemistry.
Twenty-one primary ovarian tumors and 23 metastatic sites were available for evaluation. Eighteen of 21 (86%) of ovarian sections studied expressed CD44s; 15/21 (71%) expressed CD44-4v; 14/21 (67%) expressed CD44-6v; and 12/21 (57%) expressed CD44-9v. Of 23 metastatic sites evaluated, 87% expressed CD44s. In contrast, only 5 (22%) metastases had CD44-4v and CD44-6v expression and 8 (35%) had CD44-9v immunoreactivity. None of 10 normal contralateral ovaries expressed CD44s or any splice variants. In 2 cases we had tumor available from the primary surgery, and subsequent recurrences. Both recurrences showed decreased expression of CD44-4v and CD44-6v.
Clear cell carcinoma of the ovary shows an abnormal pattern of CD44s expression and mRNA splicing when compared to the contralateral normal ovary in the same patient. Metastases of clear cell carcinoma show a downregulation in expression of some splice variants. Furthermore, we have data that suggest that as the tumors recur, CD44s and its isoforms are downregulated. Our results suggest that alternative mRNA splicing of CD44 may be important in the development of metastases from clear cell carcinoma of the ovary.
CD44是一种广泛分布于不同组织的表面糖蛋白。恶性肿瘤可能呈现更复杂的CD44表达模式，提示剪接控制丧失。本研究的目的是探讨CD44剪接变体（CD44v）在卵巢透明细胞癌中的表达及其转移潜能。
采用免疫细胞化学方法对22例卵巢透明细胞癌进行CD44标准型（CD44s）及剪接变体-4v、-6v和-9v表达情况的评估。
共有21个原发性卵巢肿瘤和23个转移部位可供评估。在研究的21个卵巢切片中，18个（86%）表达CD44s；15/21（71%）表达CD44-4v；14/21（67%）表达CD44-6v；12/21（57%）表达CD44-9v。在评估的23个转移部位中，87%表达CD44s。相比之下，仅有5个转移灶（22%）表达CD44-4v和CD44-6v，8个转移灶（35%）有CD44-9v免疫反应性。10个对侧正常卵巢均未表达CD44s或任何剪接变体。有2例患者在初次手术时获取了肿瘤组织，随后出现复发。两次复发均显示CD44-4v和CD44-6v表达降低。
与同一患者的对侧正常卵巢相比，卵巢透明细胞癌呈现CD44s表达和mRNA剪接异常模式。透明细胞癌转移灶显示某些剪接变体表达下调。此外，我们的数据表明，随着肿瘤复发，CD44s及其异构体表达下调。我们的结果提示，CD44的可变mRNA剪接可能在卵巢透明细胞癌转移的发生中起重要作用。
