Immunohistochemistry of CK5/6, CD44, and CK20 as prognostic biomarkers of non-muscle-invasive papillary upper tract urothelial carcinoma.

AIMS: Immunohistochemical (IHC) staining for CK5/6, CD44, and CK20 has been significantly associated with the prognosis of urinary bladder urothelial carcinoma and probably reflects its molecular characteristics. Because of its rarity, the IHC-based subgroups and their prognostic effects on upper tract urothelial carcinoma (UTUC) are still unclear, especially in non-muscle-invasive papillary UTUC.

METHODS AND RESULTS: IHC staining for CK5/6, CK20, and CD44 was analyzed in 211 patients with non-muscle-invasive papillary UTUC. A classification of negative, positive, or normal-pattern was found for each IHC staining. We revealed that the CK5/6Neg , CD44Neg , and CK20Pos tumours were distinctly high-risk subgroups which were associated with a high grade (CK5/6Neg , P < 0.001; CD44Neg , P < 0.001; CK20Pos , P = 0.017) and frequent IVR (CK5/6Neg , P = 0.002). Using survival analysis by Kaplan-Meier and a log-rank tests, these IHC subgroups were correlated with poor progression-free (CK5/6Neg , P = 0.001; CD44Neg , P = 0.009; CK20Pos , P = 0.031) and cancer-specific (CK5/6Neg , P = 0.009) survival. Furthermore, CK5/6Neg was an independent prognostic factor of shorter progression-free (P = 0.009) and cancer-specific (P = 0.045) survival. CK5/6 improved Harrell's C-indices for progression-free (0.68 to 0.77, P = 0.029) and cancer-specific (0.59 to 0.77, P < 0.001) survival. By combining markers, luminal-like subtypes showed poor prognoses.

CONCLUSIONS: We demonstrated that IHC staining for CK5/6, CD44, and CK20 was significantly associated with the clinicopathological characteristics and prognoses of patients with non-muscle-invasive papillary UTUC. We assume that the IHC subgroups may be correlated to the molecular characteristics of non-muscle-invasive papillary UTUC. This article is protected by copyright. All rights reserved.