Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.
In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.
The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.
The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.
Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).
Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.
About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.
“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”
The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.
The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.
SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.