Clinicopathological significance of p16, cyclin D1, Rb and MIB-1 levels in skull base chordoma and chondrosarcoma

Abstract

Objective: To investigate the expression of p16, cyclin D1, retinoblastoma tumor suppressor protein (Rb) and MIB-1 in skull base chordoma and chondrosarcoma tissues, and to determine the clinicopathological significance of the above indexes in these diseases.

Methods: A total of 100 skull base chordoma, 30 chondrosarcoma, and 20 normal cartilage tissue samples were analyzed by immunohistochemistry. The expression levels of p16, cyclinD1, Rb and MIB-1 proteins were assessed for potential correlation with the clinicopathological features.

Results: As compared to normal cartilage specimen (control), there was decreased expression of p16, and increased expression of cyclin D1, Rb and MIB-1 proteins, in both skull base chordoma and chondrosarcoma specimens. MIB-1 LI levels were significantly increased in skull base chordoma specimens with negative expression of p16, and positive expression of cyclin D1 and Rb (P < 0.05). Significantly elevated MIB-1 LI was also detected in skull base chondrosarcoma tissues, while there was negative expression of p16, cyclin D1 and Rb (P < 0.05). In skull base chordoma, p16 negatively correlated with cyclin D1 and Rb, while cyclin D1 positively correlated with Rb. Additionally, p16, cyclin D1, Rb, or MIB-1 expression showed no correlation with age, gender, or pathological classification of patients with skull base chordoma (P > 0.05). However, p16 and MIB-1 levels correlated with the intradural invasion, and expression of p16, Rb and MIB-1 correlated with the number of tumor foci (P < 0.05). Further, the expression of p16 and MIB-1 appeared to correlate with the prognosis of patients with skull base chordoma.

Conclusions: The abnormal expression of p16, cyclin D1 and Rb proteins might be associated with the tumorigenesis of skull base chordoma and chondrosarcoma.

Keywords: Cyclin D1; MIB-1; Rb; Skull base chondrosarcoma; Skull base chordoma; p16.

Fig. 1

Histopathological and immunohistochemical study of skull base chordoma and chondrosarcoma specimens. A) HE stained tissue sections; B) Tissue sections immunostained with specific antibodies against p16, cyclin D1, Rb and MIB-1 proteins. Nuclei are counterstained with hematoxylin. Scale bar, 50 μm; (C) Positive expression rate of p16, cyclin D1, Rb and MIB-1 proteins by study group.