Tissue microarray analysis of cytoskeletal actin-associated biomarkers gelsolin and E-cadherin in urothelial carcinoma.

BACKGROUND

Alterations of expression of the cytoskeletal proteins Gelsolin and E-cadherin have been implicated in urothelial carcinoma tumorigenesis. However, it is not clear how these altered expressions associate with tumor progression, nor is it clear how these protein markers provide prognostic value for urothelial carcinomas.

METHODS

Primary urothelial carcinoma tissue microarrays were constructed for 146 patients with urothelial carcinoma. Where available, four replicate tissue samples of invasive tumor, adjacent dysplastic and in situ lesions, and benign tumors were arrayed for each case, resulting in a total of 1208 tissue spots. Immunohistochemical staining for Gelsolin, E-cadherin, p53, and Ki67 (MIB-1) was performed on the arrays. For each marker, the maximum staining intensity (Max), the percentage of positive staining (Pos), and the product of both Max and Pos (MaxPos) were analyzed.

RESULTS

Compared with the benign fields, the expression of both cytoskeletal proteins decreased in premalignant and malignant lesions. For Gelsolin, decreased MaxPos was seen in premalignant and preinvasive lesions. However, with an increase in tumor grade and stage, there was a gradual increase in Gelsolin (P < 0.05 for both). E-cadherin expression decreases mainly in high-grade lesions (carcinoma in situ and Grade 3 tumors). Univariate and multivariate analyses showed that Gelsolin Max was a strong independent predictor for the probability of tumor recurrence and for early tumor recurrence in high-grade or high-stage tumors, as well as a strong indicator for tumor progression.

CONCLUSIONS

Gelsolin and E-cadherin have distinctive expression patterns. Gelsolin, but not E-cadherin, provides independent prognostic information for high-grade urothelial carcinomas.