Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases

Abstract

Background: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27kip1, and BCL2).

Methods: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation and/or progression were assessed by immunohistochemistry and correlated to the clinicopathological parameters, and survival by univariate analysis.

Results: Results showed that Fez1 protein expression was undetectable or substantially reduced in 7 of the 11 (64%) cases. Fhit protein was absent in three cases (27%). The overexpression of p53 protein was predominantly nuclear and detected in 4 of 11 cases (36%). Immunostaining for p27 was absent in 5 of 11 cases (45.5%). Five of the six remaining cases (90%) showed exclusively cytoplasmic protein expression, where, in the last case, p27 protein was detected in both nucleus and cytoplasm. Bcl2 expression with 100% of the tumor cells positive was observed in 4 of 11 (36%) cases. Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases.

Conclusions: These findings suggest that Fez1 may represent not only a molecular diagnostic marker but also a prognostic marker in CDC.

Figure 1

Representative examples of immunohistochemical analysis of Fez1, Fhit, p53, p27 and bcl2 proteins in primary Bellini's duct carcinoma of the kidney. A, Normal renal parenchyma shows uniform, cytoplasmic positive staining for Fez1 (×400). B, Fez1 protein is absent in this CDC (Case 1; ×400). An adjacent dysplastic distal duct (red arrow) shows strong Fez1 immunoreacticity. C, CDC section showing diffuse cytoplasmic staining for Fhit protein (Case 2; ×400). D, CDC neoplastic glands display strong nuclear immunoreaction for p53 oncoprotein (Case 5; ×400). Case 9 shows p27 immunoreactivity in both nucleus and cytoplasm (E) and bcl2 cytoplasmic immunostaining, red arrow (F) (×400).

Figure 2

Kaplan-Meier survival curves and associated log-rank test p-values for of eleven patients with collecting duct carcinoma of the kidney based on Fez1 (A), and Fhit (B) expression. (+); positive expression; (-) = negative expression; ■ and o = Event times.