Pathological feature change and prognostic role of primary and local recurrent chordoma in skull base

Objective To investigate the pathological characteristics and changing trend in primary and local recurrent skull base chordoma, and to analyze their correlation with the outcomes. Methods A total of 89 samples of primary and local recurrent tumors pathologically confirmed from 38 patients who were treated in Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University between February 2005 and December 2014 were retrospectively enrolled into this self-control study. After HE staining, the pathological features such as nuclear atypia, mitosis, matrix ratio, necrosis, bone invasion and pathological subtypes were analyzed. The expressions of p53, Ki-67, EGFR, VEGFR and TRAF6 were detected by immunohistochemical staining. The changes of pathological indexes as above in primary and recurrence stages were compared. Cox analyses were used to analyze the effects of above pathological indexes on the progression-free survival (PFS) of patients with primary tumor, and the effects of the changes regarding those factors on the overall survival (OS). Results Ten cases (35.7%) of classical subtype changed to myeloid subtype, while none of chondroid chordoma changed to myeloid subtype after recurrence. Twelve cases (31.6%) demonstrated necrosis companied with tumor recurrence. Twenty-five cases (73.5%) of primary tumor showed high-expression of TRAF6, and 19 cases (50.0%) had decreased expression intensity of TRAF6 after tumor recurrence. There were 16 cases (42.1%) and 15 cases (39.5%) with upregulation of P53 and EGFR respectively. Necrosis (HR=7.1, 95% CI: 1.4-37.1, P=0.006), pathological subtype (HR=3.9, 95% CI: 1.2-7.2, P=0.040) and TRAF6≥3 grade (HR=0.2, 95% CI: 0.1-0.5, P<0.001) in primary tumors were directly related to PFS, and TRAF6≥3 grade (HR=0.2, 95% CI: 0.1-0.5, P<0.010) was an independent protective factor for PFS. There was no significant difference in the OS rate among the above pathological changes. Conclusions Classical chordoma shows malignant transformation to the myeloid subtype, which is not found in chondroid subtype. The expression of TRAF6 decreases gradually with tumor recurrence, and its high expression in primary tumor is an independent protective factor for PFS. Key words: Chordoma; Skull base neoplasms; Pathology; TNF receptor-associated factor 6; Prognosis