Kida Kumiko, Ishikawa Takashi, Yamada Akimitsu, Shimada Kazuhiro, Narui Kazutaka, Sugae Sadatoshi, Shimizu Daisuke, Tanabe Mikiko, Sasaki Takeshi, Ichikawa Yasushi, Endo Itaru
Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Breast Surgery, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, Japan.
Breast Cancer Res Treat. 2016 Apr;156(2):261-9. doi: 10.1007/s10549-016-3738-7. Epub 2016 Mar 14.
Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P < 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.
醛脱氢酶1（ALDH1）已被确定为乳腺癌干细胞标志物，但其作为预后和化疗耐药预测指标的价值仍存在争议。本研究按乳腺癌亚型探讨了ALDH1对预后及化疗反应的影响。我们采用免疫组织化学方法分析了653例浸润性乳腺癌标本，并评估了临床病理因素、生存状况、新辅助化疗反应与ALDH1表达之间的相关性。在653例标本中，139例（21.3%）肿瘤细胞表达ALDH1。ALDH1表达与肿瘤体积较大、淋巴结转移、核分级较高以及HER2（+）和孕激素/雌激素受体（HR）（-）亚型显著相关。在HER2型和三阴性乳腺癌（TNBC）中显著观察到ALDH1表达。ALDH1（+）癌症患者的无病生存期（P < 0.001）和总生存期（P = 0.044）显著缩短。ALDH1表达显著影响管腔型的预后，但对TNBC和HER2富集型无影响。对于234例接受新辅助化疗的患者，ALDH1（+）病例的病理完全缓解（pCR）率显著较低（13.5%对30.3%，P = 0.003）。TNBC患者的pCR与ALDH1表达显著相关（P = 0.003）。ALDH1（+）乳腺癌往往具有侵袭性，预后较差。尽管ALDH1（+）TNBC显示出更高的化疗耐药性，但ALDH1对管腔型的预后有显著影响，而对TNBC则无影响。
