Pitfalls in the Use of Smoothelin To Identify Muscularis Propria Invasion by Urothelial Carcinoma
H Miyamoto, RB Sharma, PB Illei, JI Epstein. The Johns Hopkins Hospital, Baltimore
Background: Studies predominantly performed on cystectomy specimens have shown that antibodies against smoothelin can distinguish between muscularis mucosae (MM) (negative or weak stain) and muscularis propria (MP) (strong stain). However, studies on diagnostically difficult (TUR) specimens have not been performed.
Design: IHC for smoothelin was performed in 2 groups.
Results: The 1st cohort was 34 TUR cases where outside pathologists questioned the presence of MP invasion. Upon expert review of the H&E slides, there was no MP invasion in 18 cases. Smoothelin in MM was negative in 8/18 (44%); weakly positive (1+) in 5/18 (28%); moderately positive (2+) in 4/18 (22%); and moderately/strongly (2-3+) positive in 1/18 (6%). Smoothelin in uninvolved MP present in 8 cases was: 2+ in 2/8 (25%) and 3+ in 6/8 (75%). Smoothelin expression in MM was weaker than in MP 7/8 (88%) cases where both were present. Of 16 tumors with MP invasion, smoothelin in involved MP was: 1+ in 1/16 (6%), 2+ in 3/16 (19%), 2-3+ in 9/16 (56%), and 3+ in 3/16 (19%). Smoothelin expression in concurrent uninvolved MP was similar. The 2nd cohort was 16 cases of urothelial cancer involving muscle bundles that upon expert review were indeterminate for MM or MP, where a subsequent procedure proved their stage (T1 in 7 cases and T2 in 9 cases). Among 7 eventually proven T1 tumors, muscle bundles (presumably MM) involved by tumor: smoothelin was 0 in 3/7 (43%), 1+ in 2/7 (29%), 2+ in 1/7 (14%), and 2-3+ in 1/7 (14%). Of 9 eventually proven T2 tumors, muscle bundles (presumably MP) involved by tumor: smoothelin was 0 in 2/9 (22%), 1+ in 4/9 (44%), 1-2+ in 1/9 (11%), 2+ in 1/9 (11%), and 2-3+ in 1/9 (11%).
Conclusions: Using diagnostically difficult TUR specimens where it was difficult to distinguish MM from MP invasion, we have confirmed the relatively distinct staining pattern of smoothelin immunohistochemistry. Nonetheless, approximately 25% of cases in the current study showed overlap in the staining pattern between MM and MP. Smoothelin staining in these cases included moderate to strong positivity in MM or weak to moderate smoothelin in MP. Typically, although there were some exceptions, smoothelin immunoreactivity was stronger in MP compared to that seen in MM or smooth muscle in blood vessels at the level of the MM within the same case. However, interpretation of smoothelin in thin muscle bundles is especially problematic, when concurrent blood vessels at the level of the MM and/or MP, as internal intensity controls, are absent in the same specimen.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 93, Tuesday Afternoon