Patients whose clear cell renal cell carcinoma (RCC) tumors lack the cytoskeleton linker protein ezrin have a poorer prognosis, finds a single-center retrospective cohort study.
The number of small renal masses discovered incidentally is rising, and some of these tumors can or must be treated less aggressively, according to lead investigator Marcos Vinicius O. Ferrari, MD, urology division, A.C. Camargo Cancer Center, São Paulo, and coinvestigators. “Thus, it is important to identify molecular markers that have prognostic value that can assist physicians in therapeutic strategies.”
The investigators studied 575 consecutive patients who underwent radical or partial nephrectomy for clear cell RCC during 1985-2016. A single pathologist reclassified all cases and determined the most representative tumor areas for tissue immunohistochemistry for ezrin and moesin, proteins that link the actin cytoskeleton to the cell membrane and that play roles in cell adhesion, migration, and growth.
Results reported in Urologic Oncology showed that 18.3% of tumors were negative for ezrin and 2.8% were negative for moesin.
Compared with counterparts who had ezrin-positive tumors, patients with ezrin-negative tumors had higher pathologic T stage (P less than .001); were less likely to have incidentally discovered tumors (P = .007); and were more likely to have clinical stage III or IV disease (P = .012), synchronous metastasis (P less than .001), and an International Society of Urological Pathology histologic grade of 3 or 4 (P = .025).
Similarly, compared with counterparts who had moesin-positive tumors, patients with moesin-negative tumors had higher pathologic T stage (P = .025) and pathologic N stage (P = .007), and were more likely to have clinical stage III or IV disease (P = .027).
The 10-year rate of disease-specific survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (70% vs. 88%; P less than .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 86%; P = .065). Similarly, the 10-year rate of overall survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (68% vs. 86%; P = .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 84%; P = .142).
In multivariate analyses, ezrin negativity was associated with a near doubling of the risk of disease-specific survival events (hazard ratio, 1.89; 95% confidence interval, 1.11-3.20) and with a trend toward poorer overall survival. Moesin negativity was not independently associated with either outcome.
“Negative expression of ezrin was associated with major prognostic factors in renal cancer and significantly influenced tumor-related death,” Dr. Ferrari and coinvestigators summarize, noting that this aligns with the pattern seen in bladder and ovarian cancers, but contrasts with the pattern seen in head and neck, colorectal, cervical, and breast cancers.
“The exact mechanism by which negative ezrin expression influences tumor progression and survival rates is unknown,” they conclude. “We encourage further prospective studies to analyze ezrin to determine its value in the prognosis of clear cell RCC.”
Dr. Ferrari disclosed that he had no relevant conflicts of interest. The study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.
SOURCE: Ferrari MVO et al. Urol Oncol. 2019 Oct 22. doi: 10.1016/j.urolonc.2019.09.011.