[967] SPINK1 Expression as a Diagnostic Marker in Flat Urothelial Carcinoma In-Situ Lacks Specificity and Sensitivity

Andrew McDaniel, Nallasivam Palanisamy, Angela Wu, Rohit Mehra, Scott Tomlins, Lakshmi P Kunju. University of Michigan Health System, Ann Arbor, MI

Background: Outlier expression of SPINK1 defines a subset of clinically aggressive prostate cancers; recent reports have also suggested SPINK1 over-expression to be a sensitive and specific marker for flat urothelial carcinoma in situ (CIS). Here, we evaluated SPINK1 expression by immunohistochemistry in a spectrum of flat urothelial lesions.
Design: Immunohistochemistry (IHC) for SPINK 1 (Abnova, clone: H00006690-M01) was performed on tissue sections from 94 biopsy and resection specimens from the bladder (62 cases), ureter (26 cases) and prostatic urethra (6 cases). SPINK1 expression was evaluated in normal urothelium (NU, n=27), reactive urothelium (RU, n=24), urothelial dysplasia (UD, n=9) and CIS (n=34). Staining intensity, percentage of cells demonstrating SPINK1 expression (diffuse [>50%] vs. focal [<50%]) and urothelial staining pattern (umbrella cells only, partial thickness urothelial staining [<50% but beyond umbrella cells] vs. full thickness urothelial staining [>50%]) were assessed.
Results: Strong cytoplasmic SPINK1 staining was noted in all positive cases. Diffuse, full thickness SPINK 1 expression noted in 37%, 56% and 41% of NU, UD and CIS respectively. RU most frequently showed focal partial thickness (29%) SPINK1 expression. No SPINK 1 expression was noted in 17% of CIS cases. Umbrella cell only staining was seen in 22%, 25% and 9% cases of of NU, RU and CIS respectively. Diffuse, full thickness SPINK1 staining as a marker for CIS showed a sensitivity of 41% and a specificity of 68%. The full details of SPINK1 staining patterns are shown in the table below.

SPINK1 expression patterns in flat urothelium
 Diffuse, Full thickness (%)Diffuse, Partial thickness (%)Focal, Full thickness (%)Focal, Partial thickness(%)Umbrella cell only (%)Negative (%)
CIS (n=34)14 (41)3 (9)5 (15)3 (9)3 (9)6 (17)
NU (n=27)10 (37)2 (7)6 (22)2 (7)6 (22)1 (4)
RU (n=24)4 (17)4 (17)1 (4)7 (29)6 (25)2 (8)
UD (n=9)5 (56)3 (33)0 (0)0 (0)0 (0)1 (11)

Conclusions: In our cohort, SPINK1 showed variable expression across the spectrum of flat urothelial lesions and was not a reliable marker for CIS.
Category: Genitourinary (including renal tumors)

Wednesday, March 6, 2013 1:00 PM

Poster Session VI # 162, Wednesday Afternoon


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