Background: HER2 is a potential target of therapy in urothelial cancer (UC). Pathological case stratification according to HER2 gene amplification or HER2 protein overexpression was critical for patients’ selection in previous unsuccessful clinical trial with HER2 targeting agents. Study design: We evaluated the HER2 overexpression by immunohistochemistry (IHC) together with the amplification of the HER2 gene with chromogenic(CISH) and fluorescent (FISH) in situ hybridization in a cohort of 61 patients covering the whole spectrum of bladder UC variants, using a tissue microarray (TMA) approach. Results: IHC was available in all the 61 cases while ISH in 37 and FISH in 42. At IHC, 2/61 cases (3%) were scored 3+; 2 (3%) scored 2+; 2 (3%) scored 1+; the remaining 55 (91%) scored 0. At CISH analysis 10/37 cases (27%) were amplified, 6 cases with HER2 amplification showed positive HER2 IHC (3+, 2+, 1+). Seven cases with IHC score 0 were amplified at CISH. FISH analysis revealed an amplification in 5/42 cases (12%). The total number of HER2amplified cases was different between chromogenic and fluorescent ISH with 5 cases amplified using FISH compared to 10 with CISH. Conclusions: In clinical trials with HER2 targeting agents the candidate patients should be investigated not only by IHC but also by ISH, independently of the IHC results. Since also usual type UC can overexpress HER2 we recommend to extend the patients’ selection to all the histotypes of bladder cancer other than the micropapillary type.
Franceschini T., Capizzi E., Massari F., Schiavina R., Fiorentino M., Giunchi F. (2020). Immunohistochemical over-expression of HER2 does not always match with gene amplification in invasive bladder cancer. PATHOLOGY RESEARCH AND PRACTICE, 216(8), 1-4 [10.1016/j.prp.2020.153012].
Immunohistochemical over-expression of HER2 does not always match with gene amplification in invasive bladder cancer
Franceschini T.;Capizzi E.;Massari F.;Schiavina R.;Fiorentino M.
;
2020
Abstract
Background: HER2 is a potential target of therapy in urothelial cancer (UC). Pathological case stratification according to HER2 gene amplification or HER2 protein overexpression was critical for patients’ selection in previous unsuccessful clinical trial with HER2 targeting agents. Study design: We evaluated the HER2 overexpression by immunohistochemistry (IHC) together with the amplification of the HER2 gene with chromogenic(CISH) and fluorescent (FISH) in situ hybridization in a cohort of 61 patients covering the whole spectrum of bladder UC variants, using a tissue microarray (TMA) approach. Results: IHC was available in all the 61 cases while ISH in 37 and FISH in 42. At IHC, 2/61 cases (3%) were scored 3+; 2 (3%) scored 2+; 2 (3%) scored 1+; the remaining 55 (91%) scored 0. At CISH analysis 10/37 cases (27%) were amplified, 6 cases with HER2 amplification showed positive HER2 IHC (3+, 2+, 1+). Seven cases with IHC score 0 were amplified at CISH. FISH analysis revealed an amplification in 5/42 cases (12%). The total number of HER2amplified cases was different between chromogenic and fluorescent ISH with 5 cases amplified using FISH compared to 10 with CISH. Conclusions: In clinical trials with HER2 targeting agents the candidate patients should be investigated not only by IHC but also by ISH, independently of the IHC results. Since also usual type UC can overexpress HER2 we recommend to extend the patients’ selection to all the histotypes of bladder cancer other than the micropapillary type.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
