Emily Menendez

GU Oncology Now

Human epidermal growth factor receptor 2 (HER2) and c-MET signal activation have been involved in the pathogenesis of urothelial carcinoma (UC) subsets, with anti-programmed death-ligand 1 (PD-L1) agents commonly used for the disease. Novel therapeutic combinations that target both immune checkpoints and c-MET or HER2 pathways are currently being investigated in metastatic urothelial carcinoma (mUC), but co-expression of these molecular targets has not been characterized in mUC, and the rate of PD-L1 co-expression with c-MET and HER2 may be low.A research team sought to define the <a href="https://meetings.asco.org/abstracts-presentations/217670" target="_blank" rel="noopener">tumor protein co-expression</a> of PD-L1, c-MET, and HER2 in a cohort of patients with mUC. They shared their findings at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.A total of 143 patients with mUC were identified from an institutional database. Formalin-fixed paraffin-embedded tumor samples taken from metastatic sites and available paired primary tumors underwent immunohistochemical staining for PD-L1 (SP-142), c-MET, and HER2 expression.High expression was defined by: PD-L1, &ge;5% of infiltrated immune cells; c-MET, &ge;50% of tumor cells; HER2, score=3+ (complete membrane staining that is intense and &gt;10% of tumor cells). Simple and weighted Cohen&rsquo;s kappa statistics (&kappa;) were used to determine the agreement in expression and co-expression between paired primary and metastatic samples.The study analyzed 143 patients with mUC. Of those patients, 79 had available paired primary tumors. In primary tumors (n=79), a high expression of PD-L1, c-MET, and HER2 was seen in 15.2%, 34.2%, and 12.7% of patients, respectively. In metastatic samples (n=143), a&nbsp;high&nbsp;expression of PD-L1,&nbsp;c-MET,&nbsp;and HER2 was detected in 9.8%, 41.3%, and 9.8% of patients, respectively.Expression agreement rates among primary and metastatic specimens (n=79) were: PD-L1, 79.7% (&kappa;=.09, slight agreement); c-MET, 69.6% (&kappa;=.35, fair agreement); HER2, 84.8% (&kappa;=.17, slight agreement). Rates were driven by high prevalence of low expression.High PD-L1/c-MET co-expression was observed in 5.1% (n=4) of primary and 4.9% (n=7) of metastatic specimens. High co-expression of PD-L1/HER2 occurred in 3.8% (n=3) of primary samples and did not occur in any metastatic samples. The overall co-expression agreement rate between paired primary and metastatic samples was 55.7% (&kappa;=.22, fair agreement) for PD-L1/c-MET and 67.1% (&kappa;=.06, slight agreement) for PD-L1/HER2. However, agreement rates for high co-expression between primary and metastatic samples were significantly low (2.5% for PD-L1/c-MET and 0% for PD-L1/HER2).Among the patients with mUC in the study, tumor co-expression of high c-MET or HER2 and PD-1 was low, and agreement of high co-expression in primary and metastatic sites was rare. Investigational strategies to combine immune checkpoint inhibitors with either c-MET- or HER2-targeted agents for mUC may result in limited synergistic activity.

Metastatic Urothelial Carcinoma Shows Low Co-Expression of PD-L1, HER2, and c-MET

American Society of Clinical Oncology Genitourinary Cancers Symposium 2023

ASCO GU Symposium 2023

Researchers sought to define the tumor protein co-expression of PD-L1, c-MET, and HER2 in mUC patients. Findings were presented at the 2023 ASCO GU Symposium.

Metastatic UC Shows Low Co-Expression of PD-L1, HER2, c-MET

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