Importance of different CD44v6 expression in human gastric intestinal and diffuse type cancers for metastatic lymphogenic spreading
Importance of different CD44v6 expression in human gastric intestinal and diffuse type cancers for metastatic lymphogenic spreading
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DOI：
10.1007/bf00240138
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发表时间：
1995-08
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影响因子：
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通讯作者：
J. Dämmrich;H. Vollmers;K. Heider;H. Müller-hermelink
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作者：
J. Dämmrich;H. Vollmers;K. Heider;H. Müller-hermelink
应用免疫组织化学方法检测了42例肠型和弥漫型胃腺癌中CD44v6剪接变异体的表达，并与淋巴源性肿瘤的扩散方式进行了比较。CD44v6在慢性萎缩性胃炎肠化生中的阳性表达率为92%，而在弥漫型胃癌组中仅为17%。RNA表达分析证实了免疫组织化学数据。与正常粘膜相比，肠型癌产生的扩增产物与外显子V6杂交的模式要复杂得多，而弥漫型肿瘤不表达外显子V6。在弥漫型肿瘤中，仅有一种不表达CD44v6的窦状癌的淋巴结数目明显高于肠型癌，尤其是浸润性淋巴结转移，与原发癌一样，总是伴有CD44v6的表达。当V6阴性的弥漫型癌出现浸润性淋巴结侵犯时，V6在淋巴结转移中也有明显的表达。此外，在两种类型的原发胃癌中，浸润性淋巴转移的数量随着V6更广泛的表达而增加。提示CD44v6亚型的表达对肿瘤细胞向淋巴结的浸润性扩散具有重要意义。此外，肠上皮化生和肠型癌之间V6表达的表型相似，但在弥漫型肿瘤中不是，这可能支持科雷亚假说。
In 42 human gastric adenocarcinomas of intestinal (n=25) and diffuse types (n=17) the expression of CD44v6 splice variants was investigated immunohistochemically and compared with the pattern of lymphogenic tumor spreading. Distinct differences were observed between the two cancer types: 92% of intestinal-type tumors expressed CD44v6 as in the intestinal metaplasia in chronic atrophic gastritis, while v6 expression occurred in only 17% of diffuse-type cancers. The analysis of RNA expression confirmed the immunohistochemical data. Intestinal-type cancers yielded a much more complex pattern of amplification products hybridizing to exon v6 than did normal mucosa, whereas diffuse-type tumors did not express exon v6. Also the pattern of lymphogenic spreading was quite different between the two cancer types: in diffuse-type tumors only a sinus carcinosis without CD44v6 expression was observed in a significantly higher number of lymph nodes than in intestinal-type cancers, which showed in particular infiltrative lymph node metastases always with CD44v6 expression as in the primary tumors. When infiltrative lymph node invasion occurred in v6-negative diffuse-type cancers, v6 neoexpression was also demonstrable in the lymph node metastases. Additionally, the number of infiltrative lymphogenic metastases increased with more extensive v6 expression in primary gastric cancers of both types. These data suggest that the expression of CD44v6 isoform is important for the infiltrative spreading of tumor cells into lymph nodes. Addtionally, the phenotypic similarities in v6 expression between intestinal metaplasia and intestinal-type cancers, but not of tumors of diffuse type, may support the Correa hypothesis.