Combined use of immunohistochemical markers of basal and luminal subtypes in urothelial carcinoma of the bladder: Association with clinicopathological features and outcomes
“…[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.…”
Section: Reference [N#]mentioning
confidence: 93%
“…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 ].…”
Section: Assessment Of Ucs With Divergent Differentiation and Histolo...mentioning
confidence: 99%
“…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 ].…”
Section: Assessment Of Ucs With Divergent Differentiation and Histolo...mentioning
Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a “consensus” classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.
“…[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.…”
Section: Reference [N#]mentioning
confidence: 93%
“…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 ].…”
Section: Assessment Of Ucs With Divergent Differentiation and Histolo...mentioning
confidence: 99%
“…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 ].…”
Section: Assessment Of Ucs With Divergent Differentiation and Histolo...mentioning
Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a “consensus” classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.
“…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 ].…”
Section: Implementing Molecular Subtyping Of Bladder Cancer In Clinic...mentioning
Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A “consensus” classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.
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