Witkiewicz Agnieszka K, Dasgupta Abhijit, Nguyen Katherine H, Liu Chengbao, Kovatich Albert J, Schwartz Gordon F, Pestell Richard G, Sotgia Federica, Rui Hallgeir, Lisanti Michael P
Stem Cell Biology and Regenerative Medicine Center, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cancer Biol Ther. 2009 Jun;8(11):1071-9. doi: 10.4161/cbt.8.11.8874. Epub 2009 Jun 29.
Here, we determined the possible association of stromal caveolin-1 (Cav-1) levels with DCIS recurrence and/or progression to invasive breast cancer. An initial cohort of 78 DCIS patients with follow-up data was examined. As ER-positivity was associated with recurrence, we focused our analysis on this subset of 56 patients. In this group, we observed that DCIS progressed to invasive breast cancer in approximately 14% of the patient population (8/56), in accordance with an expected progression rate of 12-15%. Nearly ninety percent of DCIS patients (7/8) that underwent recurrence to invasive breast cancer had reduced or absent levels of stromal Cav-1. Remarkably, an absence of stromal Cav-1 (score = 0) was specifically associated with early disease progression to invasive breast cancer, with reduced time to recurrence and higher recurrence rate. All DCIS patients with an absence of stromal Cav-1 underwent some form of recurrence (5/5) and the majority (4/5) underwent progression to invasive breast cancer. This represents an overall cumulative incidence rate of 100% for recurrence and 80% for progression. An absence of stromal Cav-1 in DCIS lesions was also specifically associated with the presence of inflammatory cells. Conversely, ninety-seven percent of ER(+) DCIS patients (35/36) with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 mo), and 89% of such patients are estimated to remain free of invasive recurrence, even after 15 y. Thus, determination of stromal Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS patients.
在此，我们确定了基质小窝蛋白-1（Cav-1）水平与导管原位癌（DCIS）复发和/或进展为浸润性乳腺癌之间的可能关联。对78例有随访数据的DCIS患者的初始队列进行了检查。由于雌激素受体（ER）阳性与复发相关，我们将分析重点放在了这56例患者的亚组上。在该组中，我们观察到约14%（8/56）的患者群体中DCIS进展为浸润性乳腺癌，这与预期的12 - 15%的进展率相符。几乎90%（7/8）复发为浸润性乳腺癌的DCIS患者基质Cav-1水平降低或缺失。值得注意的是，基质Cav-1缺失（评分为0）与早期疾病进展为浸润性乳腺癌、复发时间缩短和复发率升高特别相关。所有基质Cav-1缺失的DCIS患者均经历了某种形式的复发（5/5），且大多数（4/5）进展为浸润性乳腺癌。这代表复发的总体累积发生率为100%，进展的总体累积发生率为80%。DCIS病变中基质Cav-1的缺失还与炎症细胞的存在特别相关。相反，97%（35/36）基质Cav-1水平高（评分为2）的ER（+）DCIS患者在随访期间（4 - 208个月）未出现任何浸润性复发，估计89%的此类患者即使在15年后仍无浸润性复发。因此，测定基质Cav-1水平可能是指导ER（+）DCIS患者治疗的一种有用的新生物标志物。
