Murray N P, Reyes E, Badinez L, Orellana N, Fuentealba C, Olivares R, Porcell J, Dueñas R
Hospital de Carabineros of Chile, Simón Bolívar 2200 Ñuñoa, 7770199 Santiago, Chile.
ScientificWorldJournal. 2013 May 14;2013:281291. doi: 10.1155/2013/281291. Print 2013.
HER-2 has been associated with castrate resistant prostate cancer and matrix metalloproteinase-2 (MMP-2) in the dissemination and invasion of tumor cells as well as activating angiogenesis. We present an immunocytochemical study of the effect of androgen blockade on the expression of HER-2 and MMP-2 in bone marrow micrometastasis and the surrounding stromal cells in men with prostate cancer.
A cross-sectional study of men with prostate cancer. Touch preps were obtained from bone marrow biopsies of men with prostate cancer, before and after radical prostatectomy and during androgen blockade. Micrometastasis detected with anti-PSA immunocytochemistry underwent processing with anti-HER-2 and anti-MMP-2 immunocytochemistry. Patients were defined as HER-2 positive or negative, MMP-2 negative or an MMP-2 pattern described as border or central and stromal MMP-2 defined as positive or negative. The expression of the biomarkers was compared before and after primary treatment and during androgen blockade in relation to the serum PSA at the time of sampling and duration of androgen blockade.
191 men participated, 35 men before surgery and 43 after surgery; there were no significant differences in HER-2 expression between groups, there was no MMP-2 expression centrally or stromal expression of MMP-2. In men with androgen blockade, HER-2 expression was significantly higher; there was a trend for increasing HER-2 expression up to 5 years; central MMP-2 expression significantly increased after 3 years, while stromal MMP-2 significantly increased after 6 years. MMP-2 expression both in micrometastasis and stroma was significantly associated with HER-2 expression. Expression of MMP-2 at the border of the micrometastasis was not associated with HER-2 expression and occurred in the absence of androgen blockade.
Androgen blockade decreases serum PSA by eliminating HER-2 negative prostate cancer cells. However, there is early selection of HER-2 positive cancer cells which leads to androgen independence and to increased expression of MMP-2 activity in the micrometastasis. The increased MMP-2 activity in the micrometastasis increases the expression of MMP-2 in the surrounding stromal cells and thus could promote angiogenesis and tumor growth resulting in macrometastatic androgen independent disease.
HER-2与去势抵抗性前列腺癌以及基质金属蛋白酶-2（MMP-2）在肿瘤细胞的扩散和侵袭以及激活血管生成方面有关。我们进行了一项免疫细胞化学研究，以探讨雄激素阻断对前列腺癌男性患者骨髓微转移灶及周围基质细胞中HER-2和MMP-2表达的影响。
对前列腺癌男性患者进行横断面研究。在根治性前列腺切除术前后以及雄激素阻断期间，从前列腺癌男性患者的骨髓活检中获取触片标本。用抗PSA免疫细胞化学检测到的微转移灶进行抗HER-2和抗MMP-2免疫细胞化学处理。患者被定义为HER-2阳性或阴性、MMP-2阴性或MMP-2模式描述为边界或中央型，基质MMP-2定义为阳性或阴性。比较初次治疗前后以及雄激素阻断期间生物标志物的表达与采样时血清PSA以及雄激素阻断持续时间的关系。
191名男性参与研究，35名在手术前，43名在手术后；各组之间HER-2表达无显著差异，MMP-2无中央表达或基质表达。在接受雄激素阻断的男性中，HER-2表达显著更高；HER-2表达有增加趋势，持续长达5年；3年后中央MMP-2表达显著增加，而6年后基质MMP-2显著增加。微转移灶和基质中的MMP-2表达均与HER-2表达显著相关。微转移灶边界处的MMP-2表达与HER-2表达无关，且在无雄激素阻断的情况下出现。
雄激素阻断通过消除HER-2阴性前列腺癌细胞降低血清PSA。然而，早期选择了HER-2阳性癌细胞，这导致雄激素非依赖性，并使微转移灶中MMP-2活性表达增加。微转移灶中MMP-2活性增加会增加周围基质细胞中MMP-2的表达，从而可能促进血管生成和肿瘤生长，导致大转移的雄激素非依赖性疾病。
