Elsevier

World Neurosurgery

Volume 98, February 2017, Pages 288-295
World Neurosurgery

Original Article
Differences in Dural Penetration of Clival Chordomas Are Associated with Different Prognosis and Expression of Platelet-Derived Growth Factor Receptor-β

https://doi.org/10.1016/j.wneu.2016.07.096Get rights and content

Objective

We sought to compare the prognosis of clival chordomas with different dural penetration and establish the relationship between dural penetration and platelet-derived growth factor receptor (PDGFR)-β signaling pathway.

Methods

Tumors in Type I (33 cases) showed limited dural penetration, while those in Type II (34 cases) had more serious dural penetration. Cox multivariate regression analysis was used to analyze risk factors affecting survival. Kaplan-Meier analysis measured overall survival (OS) and progression-free survival (PFS). To determine the relationship between dural penetration and PDGFR-β signaling, expression of PDGFR-β, Akt, mammalian target of rapamycin (mTOR), and phosphatase and tensin homolog (PTEN) expression was compared using immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and Western blotting.

Results

Total resection was achieved in 9 cases in Type I and 11 in Type II. There were significant correlations between OS and dural penetration (P = 0.032) and age (P = 0.034). PFS correlated significantly with dural penetration (P = 0.022), gender (P = 0.001), and degree of resection (P = 0.001). Mean OS in Type I was significantly longer than in Type II (P = 0.046). Patients aged <55 years had longer OS than those aged ≥55 years (P = 0.004). Total resection was correlated with longer PFS (P = 0.011). Among patients with tumors totally resected, mean PFS in Type I was significantly longer than in Type II (P = 0.007). Expression of PDGFR-β in Type II was higher than in Type I.

Conclusions

Clival chordomas have different degrees of dural penetration. Patients with chordomas with serious dural penetration have poorer prognosis. Higher expression of PDGFR-β is related to more serious dural penetration of clival chordomas.

Introduction

Chordomas are rare, locally invasive bone tumors, originating from notochordal remnants.1 They are often located in the axial skeleton: 50% in the sacrococcygeal region, 35% in the clivus region, and 15% in the vertebrae.2 Chordomas often adhere to and infiltrate some important structures, so it is difficult to achieve total resection, resulting in high recurrence rates. With a high recurrence rate and resistance to radiotherapy and chemotherapy, clival chordomas are still a challenge in neurosurgery. With the administration of proton radiation therapy3 and targeted drugs such as imatinib4 and rapamycin,5 prognosis has been improved but it is still far from satisfactory.

According to our clinical experience, clivus chordomas show different degrees of dural penetration: Some show little or no dura mater invasion, with extensive skull base bone invasion, and some mainly invade the dura matter, with little bone invasion. In this study, we investigated whether degree of dural penetration was related to prognosis.

The platelet-derived growth factor receptor (PDGFR)-β signaling pathway is activated in many tumors and implicated in numerous cellular processes such as growth and survival, promotion of angiogenesis, and epithelial-mesenchymal transition.6 It has been reported that PDGFR-β expression was elevated in meningiomas than dura mater and was related to migration ability of meningioma cells.7 We consider that dural penetration of clival chordomas may be related to the PDGFR-β signaling pathway. To explore the mechanisms involved in the different degrees of dural penetration, we used tissue microarray technology and immunohistochemistry to compare expression levels of protein in the PDGFR-β signaling pathway. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were performed to validate the results of immunohistochemistry.

Section snippets

Case Selection Criteria

We reviewed patients who underwent surgery between January 2008 and September 2014 in Beijing Tiantan Hospital, Capital Medical University. We found that the chordomas presented very different growth patterns: Some presented dural invasion dominated, some presented bone invasion dominated, and others presented extensive invasion. At the median level of T1-contrast sagittal magnetic resonance imaging (MRI), the line of the dorsum sellae connected to the anterior margin of the foramen magnum was

Patient Summary

There were 67 patients included in the study: 33 in Type I and 34 in Type II (Table 1). In Type I, there were 22 men and 11 women with a mean age (±SD) of 49.79 (±11.28) years. In Type II, there were 24 men and 10 women with a mean age (±SD) of 37.32 (±14.21) years. The median volume (interquartile range) of tumor was 14,000 (18,811) mm3 in Type I and 14,250.0 (16,788.42) mm3 in Type II. The most frequent complaints included diplopia (18 in Type I and 17 in Type II), headache (7 in Type I and

Discussion

OS was significantly correlated with degree of dural penetration and age. OS of Type I was significantly longer than that of Type II. We considered that it was related to the higher rate of complications in Type II. In Type I, chordomas showed little or no dural invasion. For this type of tumor, the endoscopic trans-sphenoidal approach had the advantages of easier exposure and clearer vision compared with craniotomy. Thus the endoscopic trans-sphenoidal approach was used in most cases (90.9%)

Conclusions

Clival chordomas have different degrees of dural penetration. Patients with chordomas with serious dural penetration have poorer prognosis. Higher expression of PDGFR-β is related to more serious dural penetration of clival chordomas.

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    Drs Zhai and Bai authors contributed equally to this work.

    Conflict of interest statement: The authors declare that they have no conflicts of interest. This work was supported by the Research Special Fund For Public Welfare Industry of Health (201402008), National High Technology Research and Development Program of China (863 Program, 2014AA020610), National Natural Science Foundation of China (30971005), and Innovation Foundation of Beijing Neurosurgical Institute (Youth-2014008).

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