In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 274-274
Abstract:
274 Background: Serine peptidase inhibitor Kazal type 1 (SPINK1) overexpression has been associated with poor outcomes. In one small study, loss of SPINK1 expression in urothelial carcinoma of the bladder (UCB) was associated with advanced tumor stage. We assessed the expression of SPINK1 in normal urothelium and UCB and analysed the association of SPINK1 with pathological features and clinical outcomes of patients treated with radical cystectomy (RC). Methods: The study used TMAs containing samples from 438 consecutive UCB patients treated with RC. 62 cases of normal urothelium were included as controls. A monoclonal antibody was used for immunohistochemical SPINK1 staining. SPINK1 expression of UCB was evaluated by two pathologists, blind to clinical outcome. Samples demonstrating less than 50% staining extent and 0 to 1 intensity (scale 0 to 3), were considered to have loss of expression. Results: SPINK1 expression was noted in umbrella cells of normal urothelium in 32/62 controls (52%). UCB of 254 patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with advanced pathological stage (p=0.002) and presence of lymph node (LN) metastasis (p=0.04). Within a median follow-up of 130 month (IQR 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (5-year RFS: 52±3 vs. 61±4 months; p=0.02) and cancer-specific mortality (5-year CSS: 59±3 vs. 68±3 months; p=0.03). In multivariable Cox regression analyses that adjusted for the effects of age, gender, tumor stage and grade, concomitant CIS, LN status and adjuvant chemotherapy, SPINK1 was not associated with disease recurrence (p=0.09) or cancer-specific death (p=0.12). Conclusions: While umbrella cells in normal urothelium commonly expresses SPINK1, more than half of UCB specimen exhibit loss of SPINK1 expression. Loss of SPINK1 expression is strongly correlated with local disease stage and LN metastasis. SPINK1 revealed no independent prognostic value for outcome prognostication, but it is a very promising marker for tumor staging which could be used for tailored follow-up protocols and possibly as a target for therapy as it has similarities with epidermal growth factor.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.5_suppl.274
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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