Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma: Comparative study of immunohistochemistry and fluorescent in situ hybridization

Matsubara, Hideaki; Yamada, Yoshiaki; Naruse, Katsuya; Nakamura, Kogenta; Aoki, Shigeyuki; Taki, Tomohiro; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Honda, Nobuaki

doi:10.3892/or.19.1.57

Cited by 20 publications

(22 citation statements)

References 22 publications

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“…HER2/neu has been studied in TCC with the aim to evaluate the potential for molecular targeted therapy. 24 Gene amplification and protein overexpression were first described in bladder carcinoma by Zhau et al 25 29,30 It was noted that another important element related to progression of bladder cancer is the presence of numerical alterations of some chromosomes [14][15][16][17][18] and in particular, aberrations affecting chromosome 17 16,17,22 as polysomy. 19,20,28 It has been found that polysomy of chromosome 17 is involved in the progression to detrusor-muscle invasion and has been associated with aggressive tumor behavior and recurrence of disease.…”

Section: Discussionmentioning

confidence: 97%

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

et al. 2009

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This study investigates the potential clinical significance of c-erbB-2 gene and chromosome 17 alterations by fluorescence in situ hybridization (FISH) analysis and HER2/neu overexpression by immunohistochemical staining in transitional cell carcinoma (TCC) of urinary bladder correlating the results with tumor stage and grade categories and with clinical behavior. Sixty-three cases of TCC retrieved from the files of 2 institutions were analyzed for chromosome 17 aberrations and c-erbB-2 amplification by FISH analysis and evaluated immunohistochemically for HER2/neu overexpression. Five tumors were G1, 29 intermediate grade (G2), and 29 tumors high grade (G3); 32 tumors had stage Ta, 18 tumors T1, and 13 tumors T2. We found polysomy of chromosome 17 in 58.7% of TCC with average chromosome copy number >2.26; increased number of HER2/neu gene copy was observed in 66.7% of tumors. C-erbB-2 amplification occurred in 6.3% of tumors. Immunohistochemically, 60.3% of TCC overexpressed HER2/neu and 39.7% of tumors were negative. All tumors with polysomy showed simultaneously increase of HER2/neu gene copy number of which 34/37 with protein overexpression. A statistically significant correlation between polysomy of chromosome 17 and tumor stage (P = .0003) and tumor grade (P < .0001) was found; polysomy was not seen in G1 tumors; however, 8/29 G2 tumors and 29/29 G3 tumors revealed polysomy of chromosome 17; in 8/32 Ta tumors, 14/18 T1 and 13/13 of deeply invasive tumors (T2) polysomy 17 was observed. Moreover, it was found that 7 superficial tumors (1 Ta and 6 T1) showed high polysomy with average of chromosome 17 copy number > or =3.76 as observed in all invasive tumors. The data suggest that although HER2/neu amplification, found in high grade and invasive tumors, is a rare event in TCC, polysomy of chromosome 17 is an important factor correlated with tumor stage and grade categories and could be considered a molecular marker of tumor progression with interesting diagnostic implications.

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Section: Discussionmentioning

confidence: 97%

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

et al. 2009

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“…As mentioned above, HER2 positivity has been shown to be significantly associated with further features of tumor aggressiveness such as nodal metastases [24,69,78,83] and lympho-vascular invasion [26]. Interestingly, some authors found a significantly higher HER2 positive status in metastatic lymph nodes compared with that in primary BC [26,69].…”

Section: Association Of Clinical and Pathological Parameters With Hermentioning

confidence: 93%

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

et al. 2018

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Although human epidermal growth factor receptor 2 (HER2) plays a prognostic and predictive role in breast and gastric cancer, its function in bladder cancer (BC) is still controversial. A comprehensive review of the literature has been carried out. An electronic search of databases from PubMed, Scopus, Google Scholar was implemented. The search terms were: “BC,” “bladder carcinoma,” “bladder neoplasm,” “human epidermal growth factor 2,” “HER2,” “HER-2,” “c-erbB-2,” “c-erbB2,” “erbB-2,” “erbB2,” “neu,” “marker,” “biomarker,” and “prognosis”. Results of the review consented to (a) summarize the available data on HER2 a predictor of recurrence and/or progression free survival on univariate and multivariate analysis, (b) explore the related issues in assessing HER2 status on these tumor samples, since they may severely impair its predictive function, and (c) report the state-of-the art of HER2 as a putative therapeutic target in BC and especially non-muscle invasive BC. HER2 stands out for being a prognostic factor as well as a therapeutic target in various cancers. Data from the literature concerning its use in BC provide conflicting results, probably due to the inherent complexity of BC biology. Efforts should be made to establish a suitable tumor-specific scoring system, and to assess single drugs’ efficacy in well-designed clinical trials.

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“…Reason for this wide range of HER-2 positivity [9% -81%] is that studies which include new freshly diagnosed cases show high incidence, whereas studies which included recurrent, advanced and metastatic cases show low overexpression of HER-2. 29,30,31 Therefore, HER-2 overexpression is more in low grade TCCs as compared to high grade, recurrent tumours and this expression is variable in muscle invasive tumours. Morgan et al 32 reported that BCG adjuvant therapy in nonmuscle invasive urothelial carcinoma reduced the incidence of HER-2 expression.…”

Section: Resultsmentioning

confidence: 99%

Her-2 Oncoprotein Expression in Urothelial Carcinoma

Atri¹,

Rana²,

Gupta³

2017

jemds

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BACKGROUNDLow grade non-muscle invasive transitional cell carcinoma is associated with repeated recurrences and progression to high grade tumour. Non-muscle invasive transitional cell carcinoma is associated with poor oncological outcome. Therefore, this study was undertaken to evaluate the expression of HER-2 oncoprotein in transitional cell carcinoma and further to evaluate whether expression of this oncoprotein has relation with grade of tumour and invasion of muscle.The objective of this study is to evaluate the expression of HER-2 protein in low grade, high grade and muscle invasive transitional cell carcinoma using immunohistochemistry.

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Potential for HER-2/neu molecular targeted therapy for invasive bladder carcinoma: Comparative study of immunohistochemistry and fluorescent in situ hybridization

Cited by 20 publications

References 22 publications

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review

Her-2 Oncoprotein Expression in Urothelial Carcinoma

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