Human epidermal growth factor receptor 2 expression in micropapillary urothelial carcinoma of the bladder: an analysis of 27 cases

Pathological evaluation of bladder cancer typically reveals great tumour heterogeneity, and therefore the common observation of urothelial carcinoma exhibiting a wide variety of histopathological patterns is not surprising. Some of these patterns are so distinctive that they have been recognised as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organisation (WHO) classification of tumours of the urinary system and male genital organs. The current WHO classifications clarify terminological issues and provide better definition criteria, but also incorporate some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily pathology practice. This review will discuss the features of variants of urothelial carcinoma in the context of our current clinical practice. Histological variations and new entities of bladder cancer not included in the current WHO classification of urothelial tumours will be briefly discussed.

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“…These patients have worse cancer‐specific survival. It also provides a potential role for ERBB2‐targeted therapy …”

Section: Micropapillary Urothelial Carcinomamentioning

confidence: 99%

Variants and new entities of bladder cancer

et al. 2018

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“…In keeping with such data, HER2 protein overexpression has been identified in a significantly higher proportion of cases of MPBC compared with UBC (56–87.5 vs. 31.25–50%, respectively) (34,92,97), with higher homogeneity (97), as well as in invasive conventional or variant histology UBC in combination with MPBC (97,98). In a recent series of MPBC only, the frequency of HER2 positivity was as high as 74% (99). The most recent studies have failed to identify a statistically significant association between HER2 expression and MP differentiation (100,101).…”

Section: Her2 In Mpbcmentioning

confidence: 99%

“…HER2 overexpression has been advocated as an early event in urothelial tumorigenesis and only rarely in subsequent tumor development, also because of the occurrence of HER2-positive CIS in cases of infiltrating HER2-overexpressing UBC (61), as well as its higher frequency in less advanced disease (99).…”

Section: Her2 In Mpbcmentioning

confidence: 99%

“…Studies have revealed that MPBC exhibits HER2 amplification in <42% cases (34,35,61,92), in comparison with a much lower frequency of <14% in UBC (35,75,105). As a prognostic factor, HER2 amplification (but not overexpression) exhibits a significant association with a significant increase in cancer-specific mortality (35), whereas another study failed to identify such an association in a smaller case series (34), possibly due to differences in patient selection criteria and methods, as well as the proportion of the MP component in the tumor and on the sample selected (99). On the basis of such results, it has been suggested that HER2 status may be a tool for pre-surgical risk stratification of these patients.…”

Section: Her2 In Mpbcmentioning

confidence: 99%

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Prognostic and therapeutic role of HER2 expression in micropapillary carcinoma of the bladder (Review)

et al. 2018

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Micropapillary carcinoma of the bladder (MPBC) is a variant type of infiltrating urothelial carcinoma, which portends a poor biological behavior in terms of disease stage at first diagnosis and clinical outcome; its peculiar morphology raises issues concerning the ability of tumor detection by imaging techniques and proper biopsy procedure, and the appropriate treatment for non-muscle infiltrating and muscle-infiltrating MPBC remains a matter of debate. On the basis of its established prognostic and therapeutic role in breast and gastro-esophageal cancer in the first instance, the human epidermal growth factor receptor-2 (HER2) has been investigated in selected case series of MPBC over the last 10 years. The aim of the present review was to summarize the existing evidence on HER2 status in MPBC, and to discuss its present and future utility in risk assessment and treatment choice of this uncommon, yet aggressive, disease.

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“…HER2 protein overexpression and ERBB2 amplification have also been reported in several other cancers though the therapeutic relevance of such alterations remains to be defined [9]. Overall, bladder cancer has low frequency of ERBB2 amplification (6.2% to 8.8%) [15–17], but higher rates of ERBB2 amplification have been reported in MPUC [18–21].…”

Section: Introductionmentioning

confidence: 99%

Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma

et al. 2018

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Micropapillary urothelial carcinoma (MPUC) is a rare but an aggressive variant of urothelial carcinoma. MPUC has been shown to commonly exhibit ERBB2 amplification and HER2 protein overexpression, but the frequency and distribution of these findings within micropapillary (MP) and not otherwise specified (NOS) components of tumors with mixed histology have not been addressed. Therefore, we evaluated ERBB2 amplification and HER2 expression in 43 MPUC cases by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Of the 35 tumors containing both MP and NOS components, ERBB2 amplification was present in both the MP and NOS components of 12 tumors (34.3%), in only the MP component of 11 tumors (31.4%), and exclusively in the NOS component of 4 tumors (11.4%). HER2 protein overexpression was significantly more commonly present in the MP component compared to the NOS component within the same tumor (68.6% versus 34.3%, P = .012). Overall, there was a moderately positive correlation between HER2 protein expression and ERBB2 amplification in both MP (ρ = 0.59, P < .001) and NOS (ρ = 0.70, P < .001) components. All MP/NOS areas with IHC score 3+ and none of MP/NOS areas with IHC score 0 were associated with ERBB2 amplification. We conclude that ERBB2 amplification and HER2 overexpression are preferentially but not exclusively identified in the MP component compared to the NOS component within the same tumor. Our findings identify the presence of intratumoral heterogeneity of ERBB2 amplification and HER2 expression in MPUC and provide grounds for further investigation into the mechanisms underlying the development of MPUC.

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Human epidermal growth factor receptor 2 expression in micropapillary urothelial carcinoma of the bladder: an analysis of 27 cases

Cited by 15 publications

References 26 publications

Variants and new entities of bladder cancer

Variants and new entities of bladder cancer

Prognostic and therapeutic role of HER2 expression in micropapillary carcinoma of the bladder (Review)

Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma

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