The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence

Abstract

Background: Glioblastoma carries a poor prognosis primarily because of its high rate of recurrence. The ability to predict the recurrence pattern and timing would be highly useful for determining effective treatment strategies. We examined the correlation between prognostic factors and the pattern of recurrence in patients with primary glioblastoma. In particular, we examined whether there was a correlation between the expression of CD133 and glioblastoma recurrence.

Methods: We retrospectively analyzed 112 patients with primary glioblastoma. The timing and pattern (local or distant) of the initial recurrence were obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by Western blots and immunohistochemistry, clinical (age, sex, KPS, Ki67 labeling index, surgery, ventricular entry) and genetic (IDH1, 7p, 9p, 10q, MGMT) factors.

Results: Of the 112 patients, 99 suffered recurrence. The first recurrence was local in 77 patients and distant in 22 patients. Among the factors to predict the pattern of recurrence, CD133 expression was significantly higher in distant than in local recurrence. Of the factors to predict the timing of recurrence, high CD133 expression was associated with shorter time to distant recurrence in both univariate and multivariate analyses (P = .0011 and P = .038, respectively).

Conclusions: The expression of CD133 may be a predictor of the pattern and timing of recurrence of primary glioblastoma.

Keywords: CD133; distant recurrence; glioblastoma; local recurrence; stem cells.

Fig. 1.

Definition of recurrence patterns. Representative gadolinium-enhanced MRI scans of patients treated at Tohoku University Hospital. The scans were obtained before and after surgery and at the first recurrence. (A) Local recurrence. Six months after the surgery, a local recurrence was observed, adjacent to the resection cavity (arrow). (B) Distant recurrence. Fifteen months after the surgery, an enhanced lesion was observed at a location distant from the initial lesion (arrow). (C) Twenty-six months after the surgery, a local recurrence was observed adjacent to the resection cavity. Forty months later, an enhanced lesion was seen at a distant location. Because the initial recurrence was local, this recurrence was also defined as local.

Fig. 2.

(A) Representative Western blots. The upper and lower bands show the expression of CD133 and β-actin at 130 kDa and 47 kDa, respectively. The CD133/β-actin ratio was calculated using ImageJ software. (B) Representative IHC showing glioblastoma tissue sections stained with CD133 antibody. Upper panel: CD133-positive cells are shown in brown. Lower panel: CD133-negative cells. Original magnification 400×. (C) Comparison of CD133 expression obtained using Western blots and IHC showed a positive correlation (P = .0003). The data from Western blots (on x-axis) were log-transformed. (D and E) The difference in CD133 expression between local and distant recurrence. (D) The expression of CD133 analyzed by Western blots was higher in distant recurrence than in local recurrence (P = .0002). (E) Same result was obtained for CD133 expression analyzed by IHC (P = .0043).

Fig. 3.

Kaplan–Meier curves based on CD133 expression in patients with primary glioblastoma. (A) Time to distant recurrence. Patients classified as CD133-high showed earlier dissemination (P = .0011). (B) Time to local recurrence. Patients classified as CD133-low showed earlier local recurrence (P = .012). (C) Overall survival. Patients classified as CD133-high tended to show poor survival (P = .30).