Smoothelin Expression Is a Useful Adjunct for Assessing Muscularis Propria Invasion in Bladder Cancer
IM Bovio, SZ Al-Quran, PA Drew, RW Allan. University of Florida, Gainesville, FL
Background: The invasion of muscularis propria (MP) in bladder carcinoma is a critical factor in determining appropriate therapy and prognosis. Although MP invasion can usually be determined by H&E morphology, it is often difficult to distinguish MP from the muscularis mucosa (MM), especially if the MM is hypertrophic in small biopsy and TURBT samples. Recently a novel immunohistochemical (IHC) marker, smoothelin, has been demonstrated to be preferentially expressed in MP versus MM in normal bladder tissue. However, no studies to date have explored the utility of smoothelin expression in diagnostic specimens to assess the extent of tumor invasion or its presence within the MP.
Design: We analyzed TURBT and cystectomy specimens from patients with urothelial carcinoma in which smoothelin IHC was performed from 4/08 to 9/08. These represented cases with morphologic features strongly suggestive of MP invasion, a question as to whether MP was present in the biopsy, or a question as to whether tumor was invading MP or hypertrophic MM. We semiquantitatively graded strength of reactivity as negative (0), weak (1+), moderate (2+), or strong (3+). For each specimen, vessels, MM, and MP were each scored individually.
Results: Smoothelin IHC was performed on 26 tumor cases (1 low grade and 25 high grade urothelial carcinomas) from 25 patients, and included 19 TURBTs and 7 cystectomies. 13 cases invaded the MP, 10 invaded to the LP, and 3 were non-invasive. Reactivity patterns are listed below.
|Reactivity||Vessels (%)||MM (%)||MP (%)|
|0||2/26 (8)||3/26 (12)||0/26 (0)|
|1+||23/26 (88)||22/26 (85)||2/26 (8)|
|2+||1/26 (4)||1/26 (4)||7/26 (27)|
|3+||0/26 (0)||0/26 (0)||17/26 (65)|
In every case, MP demonstrated distinctly more intense smoothelin immunoreactivity than vessels or MM. MM intensity was similar to that of vessels and never showed strong reactivity. In one consult case, smoothelin results supported an alternative diagnosis. In four cases in which there was equivocal MP involvement by H&E, smoothelin helped establish MP invasion. In all nine cases in which MP invasion was strongly suspected by H&E, smoothelin immunoreactivity was confirmatory.
Conclusions: In cases of urothelial carcinoma, smoothelin IHC is very useful in confirming the presence of MP invasion, arriving at the correct diagnosis in equivocal cases, and distinguishing between MM and MP. Furthermore, vessels within the bladder wall have similar reactivity with MM, and can be utilized as an internal intensity control for distinguishing MM and MP.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 112, Monday Morning