Unknown

Dataset Information

0

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


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.

SUBMITTER: Lalani AA 

PROVIDER: S-EPMC5732739 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Lalani Aly-Khan A AA   Gray Kathryn P KP   Albiges Laurence L   Callea Marcella M   Pignon Jean-Christophe JC   Pal Soumitro S   Gupta Mamta M   Bhatt Rupal S RS   McDermott David F DF   Atkins Michael B MB   Woude G F Vande GFV   Harshman Lauren C LC   Choueiri Toni K TK   Signoretti Sabina S  

Oncotarget 20171023 61


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  ...[more]

Similar Datasets

| S-EPMC4596765 | biostudies-literature
| S-EPMC6469103 | biostudies-literature
| S-EPMC6712567 | biostudies-literature
| S-EPMC9481706 | biostudies-literature
| S-EPMC6997072 | biostudies-literature
| S-EPMC9873321 | biostudies-literature
| S-EPMC4584049 | biostudies-literature
| S-EPMC7057441 | biostudies-literature
| S-EPMC4647139 | biostudies-literature
| S-EPMC7714499 | biostudies-literature