SIX1 Expression Correlates with Tumor Grade of Urothelial Carcinoma
Rebecca C Batiste, Rong Rong, Li-Ping Wang, Zhanyong Bing. Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Six1 is a homeobox transcription factor belonging to the evolutionarily-conserved Six1–Eya–Dach transcriptional regulatory network that is critical during embryonic development. Six1 requires interaction with the Eya family of proteins to activate the transcription of genes involved in nephrogenesis, neurogenesis and myogenesis. Mutations in either Six1 or Eya2 can lead to branchio-oto-renal syndrome. Mutations in either gene can disrupt individual protein function, Six1–DNA binding or Six1–Eya2 binding. While both genes are commonly expressed during development, their overexpression has been observed in various neoplastic states. SIX1 is aberrantly expressed in numerous cancers including those arising from breast, ovary, cervix, and liver, as well as Wilms tumor and alveolar rhabdomyosarcoma. Eya2 is required to mediate the pro-metastatic functions of Six1.
Design: The following is an immunohistochemical study of Six1 and Eya2 expression in high grade and low grade urothelial carcinoma. In the appropriate setting, the expression of Six1 and Eya2 in invasive carcinoma has also been investigated. Tumor cell nuclear staining intensity is scored in a blinded fashion using the Allred scoring system.
Results: Eighteen cases of high grade and 10 cases of low grade urothelial carcinoma were retrieved and stained for Six1 and Eya2. Twelve out of the eighteen cases of high grade urotehlial carcinoma had invasive components. The scores for non-invasive and invasive high grade urothelial carcinoma for Six1 were 6.3 +/- 2.4 and 5.9 +/- 2.3 respectively. There was no statistical difference between these two groups. The average score for low grade urothelial carcinoma for Six1 was 1.9 +/-2.5. There were significant statistical differences between low grade and high grade non-invasive and invasive carcinomas (p<0.05). Eya2 showed diffuse moderate to strong nuclear staining in both low grade and high grade noninvasive and invasive urothelial carcinoma. There were no statistical differences in the Eya2 staining among the different groups.
Conclusions: Six1 expression appears to correlate with urothelial carcinoma grade, with higher expression in the high grade tumors in both invasive and noninvasive components. There is no difference in Eya2 expression between low and high grade urothelial carcinoma.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 165, Wednesday Afternoon