Immunohistochemistry of cytokeratin (CK) 5/6, CD44 and CK20 as prognostic biomarkers of non-muscle-invasive papillary upper tract urothelial carcinoma.

AIMS

Immunohistochemical (IHC) staining for cytokeratin (CK) 5/6, CD44 and CK20 has been significantly associated with the prognosis of urinary bladder urothelial carcinoma, and probably reflects its molecular characteristics. We aimed to investigate the IHC-based subgroups and their prognostic effects on non-muscle-invasive papillary upper tract urothelial carcinoma (UTUC).

METHODS AND RESULTS

IHC staining for CK5/6, CK20 and CD44 was analysed in 211 patients with non-muscle-invasive papillary UTUC. Staining was classified as showing a negative, positive or normal pattern. We found that CK5/6-negative, CD44-negative and CK20-positive tumours were distinctly high-risk subgroups that were associated with high grade (CK5/6-negative, P < 0.001; CD44-negative, P < 0.001; CK20-positive, P = 0.017) and frequent intravesical recurrence (CK5/6-negative, P = 0.002). Using survival analysis with Kaplan-Meier and log-rank tests, we found that these IHC subgroups were correlated with poor progression-free (CK5/6-negative, P = 0.001; CD44-negative, P = 0.009; CK20-positive, P = 0.031) and cancer-specific (CK5/6-negative, P = 0.009) survival. Furthermore, CK5/6 negativity was an independent prognostic factor for shorter progression-free (P = 0.009) and cancer-specific (P = 0.045) survival. CK5/6 improved Harrell's C-indices for progression-free (0.68-0.77, P = 0.029) and cancer-specific (0.59-0.77, P < 0.001) survival. When markers were combined, 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. The IHC subgroups may be correlated with the molecular characteristics of non-muscle-invasive papillary UTUC.