Alarmo E-L, Korhonen T, Kuukasjärvi T, Huhtala H, Holli K, Kallioniemi A
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Ann Oncol. 2008 Feb;19(2):308-14. doi: 10.1093/annonc/mdm453. Epub 2007 Sep 24.
We recently showed that bone morphogenetic protein 7 (BMP7) is overexpressed in primary breast tumors. Here we explored the clinical significance of BMP7 expression in breast cancer.
This study included 483 breast cancer patients with complete clinicopathological information and up to 15 years of follow-up. Samples contained 241 lobular carcinomas, 242 ductal carcinomas, and 40 local recurrences. BMP7 protein expression was determined using immunohistochemistry.
BMP7 was expressed in 47% of the primary tumor samples and 13% of the local recurrences. The primary tumors expressed BMP7 more often than the corresponding local recurrences (P = 0.004). BMP7 expression was dependent on the tumor subtype; 57% of the lobular carcinomas but only 37% of the ductal carcinomas were BMP7 positive (P = 0.0001). BMP7 expression was associated with accelerated bone metastasis formation (P = 0.040), especially in ductal carcinomas (P = 0.033), and multivariate analysis confirmed that BMP7 is an independent prognostic indicator for early bone metastasis development (P = 0.032).
BMP7 is clearly associated with bone metastasis formation and thus might have clinical utility in identification of patients with increased risk of bone metastasis. This is the first time that bone inducing factor BMP7 has been linked to the bone metastasis process in breast cancer.
我们最近发现骨形态发生蛋白7（BMP7）在原发性乳腺癌中过表达。在此，我们探讨了BMP7表达在乳腺癌中的临床意义。
本研究纳入了483例具有完整临床病理信息且随访时间长达15年的乳腺癌患者。样本包括241例小叶癌、242例导管癌和40例局部复发癌。采用免疫组织化学法测定BMP7蛋白表达。
BMP7在47%的原发性肿瘤样本和13%的局部复发样本中表达。原发性肿瘤中BMP7的表达频率高于相应的局部复发肿瘤（P = 0.004）。BMP7表达取决于肿瘤亚型；57%的小叶癌为BMP7阳性，而导管癌仅为37%（P = 0.0001）。BMP7表达与骨转移形成加速相关（P = 0.040），尤其是在导管癌中（P = 0.033），多因素分析证实BMP7是早期骨转移发生的独立预后指标（P = 0.032）。
BMP7与骨转移形成明显相关，因此可能在识别骨转移风险增加的患者方面具有临床应用价值。这是骨诱导因子BMP7首次与乳腺癌骨转移过程相关联。
