- 作者：Michael Rink ; Kyung Park ; Bj枚rn G. Volkmer ; Evanguelos Xylinas ; Jens Hansen ; Eugene K. Cha ; Brian D. Robinson ; Richard Hautmann ; Rainer K眉fer ; Oliver Engel ; Felix K. Chun ; Rol ; Dahlem ; Mark A. Rubin ; Shahrokh F. Shariat ; Juan Miguel Mosquera
- 关键词：Urothelial carcinoma ; Radical cystectomy ; Serine peptidase inhibitor Kazal type-1 (SPINK1) ; Tumor-associated trypsin inhibitor (TATI) ; Outcome ; Survival
- 刊名：Urologic Oncology: Seminars and Original Investigations
- 出版年：November, 2013
- 年：2013
- 卷：31
- 期：8
- 页码：1716-1724
- 全文大小：2231 K
class="h4">Background
We assessed the association of serine protease inhibitor Kazal type I (SPINK1) expression with clinicopathologic outcomes in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC).class="h4">Materials and methods
Tissue microarrays comprising 438 consecutive UCB patients treated with RC between 1988 and 2003 and 62 cases of normal urothelium controls were evaluated for SPINK1 protein expression by immunohistochemistry (IHC). Semiquantitative evaluation was performed by 2 pathologists blinded to clinical outcomes (loss of expression: <50% cells or intensity 0-2).
class="h4">Results
In normal urothelium, SPINK1 expression was noted in umbrella cells of 32 of 62 controls (52%); 254 RC patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with higher pathologic stages (P = 0.002) and presence of lymph node metastasis (P = 0.04). At a median follow-up of 130 months (IQR: 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (P = 0.02) and cancer-specific mortality (P = 0.03). On multivariable analysis that adjusted for the effects of standard clinicopathologic parameters, SPINK1 was not an independent predictor of disease recurrence (P = 0.09) or cancer-specific mortality (P = 0.12).
class="h4">Conclusions
Over half of UCB patients treated with RC exhibit loss of SPINK1 expression. Loss of SPINK1 correlates with features of biologically aggressive UCB. Although SPINK1 expression did not have independent prognostic value in RC patients, it may serve as a biomarker for tumor staging and may be useful as an adjunct in clinical decision-making.