Ray Michael E, Mehra Rohit, Sandler Howard M, Daignault Stephanie, Shah Rajal B
Department of Radiation Oncology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109-0010, USA.
J Urol. 2006 Oct;176(4 Pt 1):1409-14; discussion 1414. doi: 10.1016/j.juro.2006.06.014.
Radiotherapy for biochemical prostate cancer recurrence after prostatectomy achieves durable salvage rates of only 40% to 50%. Improved methods of identifying patients unlikely to benefit from salvage radiotherapy are needed. Altered expression of the adhesion molecule E-cadherin may be associated with the invasive and metastatic phenotype. We examined the relationship between E-cadherin expression and outcomes after salvage radiotherapy.
E-cadherin expression was examined by immunohistochemistical analysis of a tissue microarray of prostatectomy tissues from patients who underwent salvage radiotherapy. The relation between E-cadherin staining, other risk factors and biochemical failure after salvage radiotherapy was analyzed using Kaplan-Meier and Cox regression methods.
Of 37 analyzable cases 25 showed aberrant E-cadherin expression, while the remainder had normal expression. At a median clinical followup of 40 months univariate analysis demonstrated that E-cadherin staining was not associated with Gleason score, extracapsular extension, surgical margin status, pre-prostatectomy or pre-radiotherapy prostate specific antigen, complete biochemical response after radiotherapy or adjunctive hormonal therapy but it was associated with seminal vesicle invasion. Two-year failure-free survival was 55% in patients with aberrant E-cadherin expression compared with 92% in patients with normal E-cadherin expression (p = 0.02). Multivariate analysis confirmed that aberrant E-cadherin expression was associated with salvage radiotherapy failure (p = 0.03).
Aberrant E-cadherin staining is associated with increased biochemical failure rates after salvage radiotherapy. Patients with biochemical failure after prostatectomy and aberrant E-cadherin expression are likely to have subclinical disseminated disease. Early systemic therapy may be warranted in these patients.
前列腺切除术后生化复发的前列腺癌患者接受放射治疗，其持久挽救率仅为40%至50%。需要改进识别不太可能从挽救性放射治疗中获益的患者的方法。黏附分子E-钙黏蛋白表达的改变可能与侵袭性和转移表型相关。我们研究了E-钙黏蛋白表达与挽救性放射治疗后结局之间的关系。
通过对接受挽救性放射治疗患者的前列腺切除组织组织芯片进行免疫组织化学分析，检测E-钙黏蛋白的表达。采用Kaplan-Meier法和Cox回归法分析E-钙黏蛋白染色、其他危险因素与挽救性放射治疗后生化失败之间的关系。
在37例可分析病例中，25例显示E-钙黏蛋白表达异常，其余病例表达正常。中位临床随访40个月，单因素分析表明，E-钙黏蛋白染色与 Gleason评分、包膜外侵犯、手术切缘状态、前列腺切除术前或放射治疗前前列腺特异性抗原、放射治疗或辅助激素治疗后的完全生化反应无关，但与精囊侵犯有关。E-钙黏蛋白表达异常的患者两年无失败生存率为55%，而E-钙黏蛋白表达正常的患者为92%（p = 0.02）。多因素分析证实，E-钙黏蛋白表达异常与挽救性放射治疗失败相关（p = 0.03）。
E-钙黏蛋白染色异常与挽救性放射治疗后生化失败率增加相关。前列腺切除术后生化失败且E-钙黏蛋白表达异常的患者可能存在亚临床播散性疾病。这些患者可能需要早期全身治疗。
