Characterization of New Immunohistochemical Markers of Renal Angiomyolipoma
LJ Eisengart, AV Yeldandi, M Zhou, BT Teh, XJ Yang. Northwestern Memorial Hospital, Chicago, IL; Cleveland Clinic, Cleveland, OH; Van Andel Institute, Grand Rapids, MI
Background: Renal angiomyolipoma (AML) is a benign neoplasm composed of blood vessels, spindle cells and mature fat in varying proportions. Rarely, these tumors exhibit epithelioid or atypical features which may have malignant behavior and which may be confused with renal cell carcinoma. Currently used markers such as HMB54 may show a very focal expression in AML causing diagnostic difficulties. Recent gene expression microarrays showed two genes highly expressed in AML in comparison with normal kidney tissues and other renal tumors; these are GREM1 and 5HER2B. The GREM1 gene encodes gremlin 1, belonging to the cysteine knot superfamily, and 5HER2B encodes 5-hydroxytryptamine (serotonin) receptor 2B.
Design: We evaluated immunohistochemical gremlin 1 and 5HER2B expression in 69 cases of renal AML (24 routine sections and 45 cases on tissue microarrays). Immunohistochemical staining was scored semiquantitatively (0 for no staining, 1 for weak staining, 2 for moderate staining and 3 for strong staining); where present, adjacent kidney tubules served as a positive internal control while vessels and kidney stromal cells served as a negative internal control.
Results: The tumors were divided into three morphological groups: 44 spindle cell predominant, 7 classic, and 18 epithelioid types. Gremlin 1 demonstrated cytoplasmic and nuclear staining in 66 of 69 cases (96%; 23/24 = 96% large sections; 43/45 = 96% TMA), which was focal in 5 cases. 5HER2B showed cytoplasmic and nuclear staining in 68 of 69 cases (99%; 24/24 = 100% large sections; 44/45 = 98% TMA), which was diffuse in all but one. Intensity of staining differed by subtype of AML. Both antibodies showed weak staining (0, focal 1+ or 1+) in the spindle cell group. Of 24 cases negative or staining weakly for Gremlin 1, 19 were spindle cell type (79%). Of the 15 cases negative or staining weakly for 5HER2B, 13 were spindle cell predominant (87%). Additionally, tumors with focal epithelioid features showed stronger staining.
Conclusions: We have verified by immunohistochemistry that both 5HER2B and Gremlin 1 are overexpressed in angiomyolipoma. Further, staining is decreased in tumors which are predominantly composed of smooth muscle and stronger in those with epithelioid features. These findings may be useful diagnostically, and also may suggest different mechanisms of tumorigenesis among various AML subtypes.
Category: Genitourinary (including renal tumors)
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 119, Monday Morning