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Immunohistochemistry of cytokeratin ( CK ) 5/6, CD 44 and CK 20 as prognostic biomarkers of non‐muscle‐invasive papillary upper tract urothelial carcinoma
Author(s) -
Jung Minsun,
Kim Bohyun,
Moon Kyung Chul
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13763
Subject(s) - immunohistochemistry , cytokeratin , pathology , medicine , carcinoma , staining , bladder cancer , cancer
Aims Immunohistochemical ( IHC ) staining for cytokeratin ( CK ) 5/6, CD 44 and CK 20 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 CK 5/6, CK 20 and CD 44 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 CK 5/6‐negative, CD 44‐negative and CK 20‐positive tumours were distinctly high‐risk subgroups that were associated with high grade ( CK 5/6‐negative, P < 0.001; CD 44‐negative, P < 0.001; CK 20‐positive, P = 0.017) and frequent intravesical recurrence ( CK 5/6‐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 ( CK 5/6‐negative, P = 0.001; CD 44‐negative, P = 0.009; CK 20‐positive, P = 0.031) and cancer‐specific ( CK 5/6‐negative, P = 0.009) survival. Furthermore, CK 5/6 negativity was an independent prognostic factor for shorter progression‐free ( P = 0.009) and cancer‐specific ( P = 0.045) survival. CK 5/6 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 CK 5/6, CD 44 and CK 20 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 .