Minsun Jung1, Bohyun Kim1, Kyung Chul Moon1,2. 1. Department of Pathology, Medical Research Centre, Seoul National University College of Medicine, Seoul, Republic of Korea. 2. Kidney Research Institute, Medical Research Centre, Seoul National University College of Medicine, Seoul, Republic of Korea.
Abstract
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.
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.
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