Utility of Double Immunohistochemical Staining for Smoothelin/Pancytokeratin in the Staging of Urothelial Carcinomas
M Dvorakova, R Dhir, SI Bastacky, G Cai, W Khalbuss, MB Acquafondata, AV Parwani. University of Pittsburgh Medical Center (UPMC), Pittsburgh
Background: Pathologic staging of urothelial carcinomas reflects the depth of tumor invasion and is important for both therapy and prognosis. The distinction between muscularis mucosae (pT1) and detrusor muscle (at least pT2) involvement can be challenging in unoriented and limited specimens, such as biopsies and transurethral resections (TURBT). Smoothelin was recently described as a promising marker of terminally differentiated contractile smooth muscle cells not expressed in muscularis mucosae. The goal of our study was to evaluate the contribution of double immunohistochemistry (DIHC) for smoothelin and cytokeratin in staging of invasive urothelial carcinomas especially in fragmented, cauterized or scant TURBT material.
Design: Twenty-six pT3 cystectomies, 25 TURBT specimens and a tissue microarray of 120 TURBT specimens from 118 patients with urothelial carcinoma invasive into the detrusor muscle were stained with DHIC for cytokeratin (combination of Cam 5.2 and AE1/3, Biocare Medical, red chromogen) and smoothelin (Chemicon International, brown chromogen). Staining intensity was graded on a scale 0-3+ (0- <5%, 1+ 5-10%, 2+ 11-50%, 3+ >50%).
Results: All cystectomies (26/26) and TURBTs (25/25) showed a significant difference in smoothelin staining between the detrusor muscle (3+ cytoplasmic staining) and muscularis mucosae (0-1+ staining). Staining of variable intensity (1-2+) was also observed in the smooth muscle of vessel walls, especially in large caliber arteries of muscularis propria. Smoothelin did not stain desmoplastic areas in lamina propria invasive urothelial carcinomas. Twenty one cores (21/120) of the tissue microarray contained an area of detrusor muscle invasion; carcinoma cells infiltrating detrusor muscle fibers were highlighted by smoothelin/cytokeratin DIHC in 20/21 cases.
Conclusions: (1) Smoothelin proved to be a reliable marker to differentiate detrusor muscle from muscularis mucosae, desmoplastic areas in lamina propria or smooth muscle of vessel walls; (2) smoothelin/cytokeratin DIHC helped to highlight invasion into detrusor muscle in limited material of TURBT and tissue microarray; (3)smoothelin/cytokeratin cocktail may be a useful diagnostic tool in the assessment of challenging bladder biopsies.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 93, Tuesday Morning