Afify Alaa, Pang Lori, Howell Lydia
Department of Pathology and Laboratory Medicine, UC Davis Health System, University of California-Davis, 4400 V Street, Sacramento, CA 95817, USA.
Appl Immunohistochem Mol Morphol. 2007 Dec;15(4):446-50. doi: 10.1097/01.pai.0000213154.49063.22.
CD44 is an 85 to 90 kd integral transmembrane protein encoded by a single 20-exon gene located on the short arm of chromosome 11. In the standard form (CD44s), 10 of the 20 exons are transcribed. Multiple variant isoforms exist (CD44v1-10) which arise from alternate mRNA splicing of the remaining 10 exons. In contrast to the standard form of CD44, which is almost ubiquitously expressed, splice variants are highly restricted in their expression in normal or malignant tissues. The purpose of this study was to evaluate the extent to which metastatic adenocarcinomas in effusions express CD44s, CD44v6, and CD44v3-10 and to assess their diagnostic utility in distinguishing reactive mesothelial cells from adenocarcinomas. Archival paraffin-embedded cell blocks of serous fluids from 23 cases of benign effusions containing reactive mesothelial cells and 45 cases of malignant effusions with metastatic adenocarcinoma (18 ovarian, 11 pulmonary, 9 gastrointestinal, and 7 breast) were retrieved from the surgical pathology files. The cytopathology of all cases was reviewed to confirm the diagnosis. Immunohistochemistry was performed on all cases using antibodies for CD44s, CD44v6, and CD44v3-10 (Bender MedSystems, CA). Positive staining was defined as distinct linear membrane staining. Strong staining in at least 10% of the tumor cells was required to consider the case positive for the particular marker. In benign effusions mesothelial cells expressed CD44s in 22 cases (96%), CD44v6 in 1 cases (4%) and CD44v3-10 in 0 cases (0%). In contrast neoplastic cells in malignant effusions expressed CD44s in 11 cases (24%), CD44v6 in 21 cases (47%), and CD44v3-10 in 39 cases (87%). We concluded that CD44s and CD44v3-10 are useful markers that can be applied to cytologic specimens. CD44s immunostaining can be used as a reliable marker to identify reactive mesothelial cells, meanwhile CD44v3-10 immunostaining can detect majority of adenocarcinomas in malignant effusions.
CD44是一种85至90kd的整合跨膜蛋白，由位于11号染色体短臂上的一个含20个外显子的单基因编码。在标准形式（CD44s）中，20个外显子中的10个被转录。存在多种可变异构体（CD44v1 - 10），它们由其余10个外显子的可变mRNA剪接产生。与几乎普遍表达的CD44标准形式不同，剪接变体在正常或恶性组织中的表达受到高度限制。本研究的目的是评估积液中的转移性腺癌表达CD44s、CD44v6和CD44v3 - 10的程度，并评估它们在区分反应性间皮细胞和腺癌方面的诊断效用。从手术病理档案中检索出23例含有反应性间皮细胞的良性积液和45例伴有转移性腺癌的恶性积液（18例卵巢癌、11例肺癌、9例胃肠道癌和7例乳腺癌）的存档石蜡包埋细胞块。复查所有病例的细胞病理学以确认诊断。对所有病例使用针对CD44s、CD44v6和CD44v3 - 10的抗体（Bender MedSystems，加利福尼亚州）进行免疫组织化学检测。阳性染色定义为明显的线性膜染色。若要认为病例对特定标志物呈阳性，至少10%的肿瘤细胞需有强染色。在良性积液中，间皮细胞在22例（96%）中表达CD44s，在1例（4%）中表达CD44v6，在0例（0%）中表达CD44v3 - 10。相比之下，恶性积液中的肿瘤细胞在11例（24%）中表达CD44s，在21例（47%）中表达CD44v6，在39例（87%）中表达CD44v3 - 10。我们得出结论，CD44s和CD44v3 - 10是可应用于细胞学标本的有用标志物。CD44s免疫染色可作为识别反应性间皮细胞的可靠标志物，同时CD44v3 - 10免疫染色可检测恶性积液中的大多数腺癌。
