Higashikawa K, Yokozaki H, Ue T, Taniyama K, Ishikawa T, Tarin D, Tahara E
First Department of Pathology, Hiroshima School of Medicine, Japan.
Int J Cancer. 1996 Mar 28;66(1):11-7. doi: 10.1002/(SICI)1097-0215(19960328)66:1<11::AID-IJC3>3.0.CO;2-1.
We generated DNA probes for CD44 variable region exons 11 (v6) to 14 (v9) and also for intronic sequences and examined the expression of aberrant CD44 transcripts in digestive tract carcinomas, colorectal adenomas and intestinal metaplasia of the stomach. The study used the reverse transcription-polymerase chain reaction/Southern blot technique. Among the probes generated, the CD44 intron 9 probe was the best for distinguishing cancer tissue from normal tissue in adenocarcinomas of the colorectum or stomach. All the colorectal adenocarcinomas revealed overexpression of CD44 variants containing the intron 9 sequence compared with the corresponding normal colorectal mucosa. The overexpression of such abnormal CD44 variants was observed from an early stage in colorectal cancer and did not correlate with nodal or distant metastatic status. In intestinal metaplasia of the stomach, aberrant CD44 transcripts with characteristic 2 or 3 peaks containing intron 9 were observed. On the other hand, in oral and esophageal squamous cell carcinomas and corresponding normal squamous epithelia, overexpression of CD44 variants with variable exons and retained intron 9 sequence was frequently observed in both cancer tissue and corresponding normal mucosa. Examination of the expression of CD44 variants in a screening panel of normal tissues from the whole body revealed that overexpression of transcripts containing exon 11 and 14 as well as of the intron 9 sequence was constantly observed in tissues with squamous epithelia like skin, oral mucosa, esophagus and uterine cervix. Expression of these variants was also found in urinary bladder, respiratory tract, pancreas and salivary glands. Our results overall indicate that detecting the overexpression of abnormal CD44 transcripts, especially ones containing the intron 9 sequence, could be a powerful indicator for the presence of adenocarcinomas in the digestive tract. However, it is not applicable for the diagnosis of malignancies originating from squamous epithelia.
我们制备了针对CD44可变区外显子11（v6）至14（v9）以及内含子序列的DNA探针，并检测了消化道癌、大肠腺瘤和胃黏膜肠化生中异常CD44转录本的表达。该研究采用逆转录-聚合酶链反应/ Southern印迹技术。在所制备的探针中，CD44内含子9探针在区分结直肠癌或胃癌的癌组织与正常组织方面效果最佳。与相应的正常大肠黏膜相比，所有结直肠癌均显示含有内含子9序列的CD44变体过表达。这种异常CD44变体的过表达在结直肠癌早期即可观察到，且与淋巴结或远处转移状态无关。在胃黏膜肠化生中，观察到含有内含子9的具有特征性2或3个峰的异常CD44转录本。另一方面，在口腔和食管鳞状细胞癌及相应的正常鳞状上皮中，癌组织和相应正常黏膜中均经常观察到具有可变外显子且保留内含子9序列的CD44变体过表达。对来自全身的正常组织筛选面板中CD44变体表达的检测显示，在具有鳞状上皮的组织如皮肤、口腔黏膜、食管和子宫颈中，始终观察到含有外显子11和14以及内含子9序列的转录本过表达。在膀胱、呼吸道、胰腺和唾液腺中也发现了这些变体的表达。我们的结果总体表明，检测异常CD44转录本的过表达，尤其是含有内含子9序列的转录本，可能是消化道腺癌存在的有力指标。然而，它不适用于源自鳞状上皮的恶性肿瘤的诊断。
