Double Immunohistochemistry for CK20/ Ki67 in the Diagnosis of Neoplastic and Non-Neoplastic Bladder
SN Kamat, M Acquafondata, S Bastacky, AV Parwani. University of Pittsburgh, Pittsburgh, PA
Background: Distinguishing neoplasia from reactive atypia in bladder is difficult on histopathology alone. Previous studies have demonstrated CK20 and Ki67 as objective markers for assessing neoplasia/dysplasia in bladder. We describe the utility of CK20/ Ki67 double IHC (DIHC) as a tool for differentiating benign, dysplastic, carcinoma in situ (CIS) and invasive lesions in bladder.
Design: 100 cases (62 biopsies (Bx), 14 transurethral resection of tumor, and 24 radical cystectomies) were retrieved from our surgical pathology files which included 28 benign/reactive, 12 dysplasia/CIS, and 60 urothelial carcinomas (UC). H&E and CK20/Ki67 DIHC slides were reviewed. CK20 cytoplasmic stain was evaluated as 0 (no staining), 1+ (patchy, weak intensity), 2+ (<50%, moderate intensity) and 3+ (>50% strong intensity). Location of the staining in upper 1/3rd-umbrella cells, upper 2/3rd or full-thickness urothelium (including the basal layer) was documented. Ki67 was scored as 0 (no staining), 1+ (<15% tumor), 2+ (25-50%), 3+ (50-75%) and 4+ (>75%).
Results: Benign/reactive, 27/28(96%) cases were 2-3+ CK20 in the umbrella cells; 9/28 (32%) cases showed 2+ Ki67 in the basal epithelium. 5/5 (100%) cases of dysplasia showed 2-3+ CK20 in upper 2/3 urothelium sparing the basal layer and 1+ Ki67. 7/7 (100%) cases of CIS (Bx) had 3+ full-thickness (focal or diffuse) CK20 staining and 2+ Ki67. 9/9(100%) cases of bladder resections for invasive carcinoma with CIS showed 3+ full thickness CK20 with 1+ and 2+ Ki67 in 6 and 3 of these 9 cases respectively. In UC, CK20 was 3+ full thickness positive in 41/60 (68%) cases (4 squamous cell, 7 invasive low-grade and 30 invasive high-grade); CK20 was negative in 19/60 (32%) cases (4 poorly differentiated, 4 small cell/ neuroendocrine, 8 sarcomatoid, 3 squamous cell), Ki67 varied from 1+ to 4+ in all high grade UC and 0 to 1+ in invasive low grade UC.
Conclusions: Our study demonstrates that CK20/Ki67 DIHC may be a useful diagnostic tool in the assessment of bladder lesions. Benign/reactive cases consistently showed CK20+ in umbrella cells with majority Ki67 negative. Dysplastic lesions were CK20 positive in upper 2/3rd of urothelium with a low Ki 67 index. CIS and UC demonstrated full thickness CK20/Ki67 dual staining. CK20/Ki67 further aided in subclassification, negative CK20 in neuroendocrine/ small cell and poorly differentiated carcinomas and Ki67 correlated with the histomorphological diagnosis, very high Ki67 in small cell/ neuroendocrine carcinomas while lower index in squamoid differentiation.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 126, Monday Morning