Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression

Aly Khan A. Lalani, Kathryn P. Gray, Laurence Albiges, Marcella Callea, Jean Christophe Pignon, Soumitro Pal, Mamta Gupta, Rupal S. Bhatt, David F. McDermott, Michael B. Atkins, G. F.Vande Woude, Lauren C. Harshman, Toni K. Choueiri, Sabina Signoretti

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    16 Citations (Scopus)

    Abstract

    In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

    Original languageEnglish
    Pages (from-to)103428-103436
    Number of pages9
    JournalOncotarget
    Volume8
    Issue number61
    DOIs
    Publication statusPublished - 1 Jan 2017

    Keywords

    • C-Met
    • Metastasis
    • PD-L1
    • Primary
    • Renal cell carcinoma

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