[1010] Variability of Smoothelin Expression in Muscularis Propria of the Urinary Bladder: A Diagnostic Pitfall

Umer N Sheikh, Muhammad I Zulfiqar, Asif Shahab, Paul J Kowalski, Hong Qu. Saint John Hospital & Medical Center, Detroit, MI

Background: Smoothelin is a smooth muscle-specific cytoskeletal marker expressed strongly in terminally differentiated smooth muscle cells. It has been postulated that in the urinary bladder, immunohistochemistry for smoothelin may help separate conventional and hyperplastic muscularis mucosa (MM) from the true muscularis propria (MP) to aid in accurate cancer staging. We studied the expression pattern of smoothelin in the MP and investigated the possible impact of tumor invasion, chronic inflammation, and fibrosis, on the expected staining pattern.
Design: A total of 24 cystectomies were retrieved from St. John Hospital's surgical pathology archive. Out of these 24 cases, 70 full-thickness representative sections were selected with 1 to 6 sections per case. Of these 70 sections, 14 were from dome, 11 from trigone, 12 from ureteric orifice, and 33 from the remainder of the bladder. The MP was divided into the upper {superficial 50 % (UMP)} and lower {deep 50% (LMP)}, and was further evaluated in H&E slides for the presence of invasive carcinoma, chronic inflammation, and fibrosis. These sections were subsequently immunostained with antibody to smoothelin (R4A mab; Cell Marque Corp, CA). The staining score was evaluated for staining intensity (0 to 3+) and % positive cells (focal, moderate or diffuse). Smooth Muscle Actin (SMA) was done in 5/10 of the sections containing significant fibrosis to confirm MP.
Results: With smoothelin, the MP typically showed moderate to strong (2 to 3+) and diffuse staining in 57/70 (81%) and 28/70 (40%) of LMP and UMP, respectively. In the 28 UMP sections, tumor invasion, inflammation, fibrosis and scarring were either absent or minimal. In the remaining 42 UMP sections, which stained negative to weak (0 to 1+), tumor invasion, extensive inflammation, or fibrosis and scarring were seen in 21/42 (50%) sections. SMA showed diffuse positivity in all of those UMP bundles, which had lost their reactivity to smoothelin due to fibrosis. However, in 19% of LMP and 10% of UMP, no definitive factor was seen that affected the smoothelin staining.
Conclusions: Our data shows that MP smoothelin expression varies considerably. This variability is likely related to the presence of tumor invasion, chronic inflammation, and fibrosis. Since most of these changes occur frequently in the UMP, a critical determinant for cancer staging especially in the setting of transurethral resections of bladder tumors (TURBTs), smoothelin staining is highly unpredictable. In conclusion, caution should be taken when using this antibody as a decision making tool for MP in TURBTs.
Category: Genitourinary (including renal tumors)

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 88, Tuesday Afternoon


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