Pirinen R, Hirvikoski P, Böhm J, Kellokoski J, Moisio K, Virén M, Johansson R, Hollmén S, Kosma V M
Department of Pathology & Forensic Medicine, University of Kuopio, Finland.
Hum Pathol. 2000 Sep;31(9):1088-95. doi: 10.1053/hupa.2000.16277.
The expression of CD44 standard form (CD44s) and variant isoforms v3 and v6 was analyzed in 233 resected non-small cell lung carcinoma (NSCLC) specimens by immunohistochemistry (IHC), and the mRNA status of CD44v3 and CD44v6 in a cohort of samples was determined by in situ hybridization (ISH) and further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of CD44s, CD44v3, and CD44v6 was correlated with clinicopathologic variables and survival. The expression of CD44v3 and v6 was reduced in 97% and 90% of the adenocarcinomas and in 86% and 74% of the large cell/anaplastic carcinomas, respectively, as compared with squamous cell carcinomas, where they were reduced in 53% and 51% of the cases (P = .0001 and P = .004 for v3 and v6). The corresponding values for CD44s were 92%, 70%, and 51%, respectively (P = .011). The reduced CD44s and CD44v6 expression was associated with lymph node metastases (P = .03 and P = .005, respectively) and the reduced expression of CD44s also with advanced stage (P = .04). Recurrences during the follow-up were more often found within the tumors showing reduced expression of CD44v3 (P = .04). Combining ISH and IHC results showed that CD44v3 and v6 mRNA were not always processed into protein, suggesting a regulation disturbance posttranscriptionally since malignant transformation of cells has occurred. In survival analyses, the reduced expression of CD44s and CD44v3 was associated with a shortened disease-free survival (P = .04 and P = .01, respectively). In multivariate analysis, CD44v3 retained its independent prognostic value (P = .03). These results emphasize the value of CD44, and especially the v3 variant isoform in the behavior of NSCLC.
通过免疫组织化学（IHC）分析了233例切除的非小细胞肺癌（NSCLC）标本中CD44标准型（CD44s）以及变异体v3和v6的表达情况，并通过原位杂交（ISH）确定了一组样本中CD44v3和CD44v6的mRNA状态，随后通过逆转录聚合酶链反应（RT-PCR）进一步证实。CD44s、CD44v3和CD44v6的表达与临床病理变量及生存率相关。与鳞状细胞癌相比，腺癌中CD44v3和v6的表达分别在97%和90%的病例中降低，大细胞/间变性癌中分别在86%和74%的病例中降低，而鳞状细胞癌中CD44v3和v6降低的病例分别为53%和51%（v3和v6的P值分别为0.0001和0.004）。CD44s的相应值分别为92%、70%和51%（P = 0.011）。CD44s和CD44v6表达降低与淋巴结转移相关（P值分别为0.03和0.005），CD44s表达降低还与晚期相关（P = 0.04）。随访期间，复发更常出现在CD44v3表达降低的肿瘤中（P = 0.04）。结合ISH和IHC结果显示，CD44v3和v6的mRNA并非总是加工成蛋白质，这表明自细胞发生恶性转化后转录后调控出现紊乱。在生存分析中，CD44s和CD44v3表达降低与无病生存期缩短相关（P值分别为0.04和0.01）。在多变量分析中，CD44v3保留了其独立的预后价值（P = 0.03）。这些结果强调了CD44的价值，尤其是v3变异体在NSCLC行为中的价值。
