Combined use of immunohistochemical markers of basal and luminal subtypes in urothelial carcinoma of the bladder: Association with clinicopathological features and outcomes

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation

“…[31] CK5/6, CK14, GATA3, FOXA1 Bas, Lum, DP Bas: more likely to achieve a pathological response to NAC. [32] CK5, GATA3, CK20 Bas, Lum, DN, DP No significant differences in survival among subtypes.…”

“…SD-UC should be distinguished by pure squamous cell carcinoma (SCC), which is a distinct non-urothelial histotype usually associated to a poor clinical outcome [ 97 ]. Tumors in the Bas molecular subtype according to various classifications are often enriched with squamous histology [ 7 , 27 , 29 , 31 , 32 , 36 , 47 , 101 , 102 , 106 , 107 ], and cluster together with squamous neoplasms of the lung, head, and neck according to the molecular pan-cancer analysis [ 10 , 101 , 111 , 112 ], though a complete biunivocal correspondence between transcriptional and morphological features does not exist [ 38 ]. According to the recent consensus classification, SD accounts for as many as 42% of all Bas tumors [ 13 ].…”

“…In a previous study by Choi et al, Bas tumors were analyzed through molecular profiling and could be reliably classified by the expression of immunohistochemical markers, such as CK5/6 and CD44, along with lack of CK20, in keeping with other reports [ 34 ]; in the same study, Bas MIBCs were enriched with squamous and sarcomatoid features and often associated with advanced/metastatic disease at presentation [ 7 , 105 ]. Accordingly, in the MIBC series assessed by Ravanini et al [ 32 ], including 17 sarcomatoid tumors, 88% (15/17) of them belonged either to the Bas (CK5+/CK20−, 67%) or to the DN (CK5−/CK20−, 33%) subtype. In keeping with that, in the recent consensus molecular classification by Kamoun et al, SCs were overrepresented within the Ba/Sq group [ 13 ], and recently it has been suggested that sarcomatoid differentiation might result for de-differentiation of a subset of progressing Bas tumors [ 47 , 126 ], being enriched for loss of adherence genes, including CDH1 and Claudins, and overexpression of EMT transcriptional factor SNAI2 [ 126 ].…”

“…Divergent Differentiation/Histological Subtype IHC-Based Molecular Cluster [13,22,25,26,48,101] Squamous Mostly basal [22,25,27,35,102] Glandular Variable [13,32,67,101,[103][104][105] Micropapillary Mostly luminal (LumNS) [13,68,[106][107][108][109] Nested and large nested Mostly luminal (LumP) [27,29,69,101,107,110] Plasmacytoid Mostly luminal [23,26,29,32,34] Sarcomatoid Variable…”

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 1: General Issues and Marker Expression

“…Furthermore, such differences may be seen by comparing primary tumors and their matched metastases, mostly in the Ba/Sq subtype, though at low levels [ 70 , 97 , 98 , 99 ], possibly due to (1) the prevalence of single clones within heterogeneous primaries, (2) protein expression switches due to chemotherapy-induced enrichment in mutations, and/or (3) interactions with the microenvironment in the two different anatomical sites [ 70 , 99 , 100 ]. In keeping with that, high concordance rates were described in a recent study assessing primary chemotherapy-naïve BCs and their metastases by the expression of luminal (FOXA1, GATA3) and basal (CK5/6, CK14) markers [ 101 ].…”