Telomerase activity in ductal carcinoma in situ and invasive breast cancer

被引:48
|
作者
Umbricht, CB
Sherman, ME
Dome, J
Carey, LA
Marks, J
Kim, N
Sukumar, S
机构
[1] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[3] Duke Univ, Dept Surg, Durham, NC USA
[4] Geron Corp, Menlo Park, CA USA
关键词
telomerase; breast cancer; ductal carcinoma in situ; microdissection; cancer progression;
D O I
10.1038/sj.onc.1202714
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The increasing number of breast carcinoma in situ detected by screening procedures makes it imperative to develop improved markers to stratify the risk of invasive cancer, Telomerase is detectable in invasive cancer, but not in normal tissues. We have microdissected frozen tissue blocks containing both DCIS and invasive cancer to assay the telomerase activity of these two lesions. The 46 available cases of concurrent DCIS and invasive breast cancer resulted in 43 DCIS samples and 38 invasive cancer samples adequate for analysis. Seventy per cent of the DCIS and all invasive cancer samples tested had detectable telomerase activity. In addition, we analysed telomerase activity in ten cases of DCIS that were not associated with invasive cancer, and detected telomerase activity in seven (70%). Mixing experiments showed no evidence of telomerase inhibitors in telomerase negative samples. Furthermore, periductal inflammatory infiltrates were shown to be a potential confounding source of telomerase activity. Since DCIS lesions appear to be heterogeneous with respect to telomerase activity, and telomerase activation appears to precede the development of invasive cancer, telomerase activity may be a useful adjunct in stratifying the risk of developing invasive breast cancer in patients with DCIS.
引用
收藏
页码:3407 / 3414
页数:8
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