High expression of survivin independently correlates with tumor progression and mortality in patients with skull base chordomas

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OBJECTIVE

The object of this study was to clarify the expression characteristics and prognostic value of survivin in skull base chordomas.

METHODS

In this retrospective study, the authors measured the expression of survivin at the mRNA level in 81 samples from 71 patients diagnosed with skull base chordomas at their hospital in the period from July 2005 to January 2015. Clinical data collection, follow-up, and survival analyses were performed, and correlations were analyzed.

RESULTS

Of the 71 patients, 50 had primary chordomas with a mean survivin expression level of 1.09; the other 21 patients had recurrent chordomas with a mean survivin expression level of 2.57, which was 2.36 times higher than the level in the primary chordoma patients (p < 0.001, Mann-Whitney U-test). In addition, an analysis of 18 paired samples derived from 9 patients showed that the expression level of survivin was 2.62 times higher in recurrent tumors than in primary tumors (p = 0.002, paired t-test). The Spearman rank correlation coefficient method showed that the expression level of survivin was positively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T1-weighted sequences (RT1; rs = 0.274, p = 0.021) and was negatively correlated with the mean ratio of tumor signal intensity to the signal intensity of surrounding brainstem on T2-weighted sequences (RT2; rs = −0.389, p = 0.001). A multivariate Cox proportional-hazards model suggested that pathology (p = 0.041), survivin expression level (p = 0.018), preoperative Karnofsky Performance Status (KPS; p = 0.012), and treatment history (p = 0.009) were independent prognostic factors for tumor progression. Survivin expression level (p = 0.008), preoperative KPS (p = 0.019), tumor diameter (p = 0.027), and intraoperative blood loss (p = 0.015) were independent prognostic factors for death.

CONCLUSIONS

Survivin expression level and preoperative KPS were independent significant prognostic factors for tumor progression and death in skull base chordoma patients. Recurrent skull base chordomas and chordomas with high RT1 and low RT2 were likely to have high survivin expression. Other independent risk factors related to tumor progression included conventional pathology and treatment history, whereas additional mortality-related risk factors included larger tumor diameter and greater intraoperative blood loss.

ABBREVIATIONS ELS = expression level of survivin; GTR = gross-total resection; KPS = Karnofsky Performance Status; OS = overall survival; PFS = progression-free survival; PR = partial resection; RCE = ratio of mean signal intensity of tumor to mean signal intensity of surrounding brainstem on contrast-enhanced MRI sequence; RT1 = ratio of mean signal intensity of tumor to mean signal intensity of surrounding brainstem on T1-weighted MRI sequence; RT2 = ratio of mean signal intensity of tumor to mean signal intensity of surrounding brainstem on T2-weighted MRI sequence; SBC = skull base chordoma; STR = subtotal resection.
Article Information

Contributor Notes

Correspondence Junting Zhang: Beijing Tiantan Hospital, Beijing, People’s Republic of China. zhangjunting2003@aliyun.com.INCLUDE WHEN CITING Published online January 11, 2019; DOI: 10.3171/2018.8.JNS181580.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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References
  • 1

    Abdel-Aziz AMohamed MAAkl FMTaha AN: Survivin expression in medulloblastoma: a possible marker for survival. Pathol Oncol Res 19:4134192013

    • Search Google Scholar
    • Export Citation
  • 2

    Ambrosini GAdida CAltieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:9179211997

  • 3

    Chen CYang HLChen KWWang GLLu JYuan Q: High expression of survivin in sacral chordoma. Med Oncol 30:5292013

  • 4

    Chen JHChen KYMa HIYu CPNieh SLee HS: Cortactin, fascin and survivin expression associated with clinicopathological parameters in brain gliosarcoma. Chin J Physiol 53:2342442010

    • Search Google Scholar
    • Export Citation
  • 5

    Choy WTerterov SKaprealian TBTrang AUng NDeSalles A: Predictors of recurrence following resection of intracranial chordomas. J Clin Neurosci 22:179217962015

    • Search Google Scholar
    • Export Citation
  • 6

    Eriksson BGunterberg BKindblom LG: Chordoma. A clinicopathologic and prognostic study of a Swedish national series. Acta Orthop Scand 52:49581981

    • Search Google Scholar
    • Export Citation
  • 7

    Evers PDLogan JESills VChin AI: Karnofsky performance status predicts overall survival, cancer-specific survival, and progression-free survival following radical cystectomy for urothelial carcinoma. World J Urol 32:3853912014

    • Search Google Scholar
    • Export Citation
  • 8

    Flanagan AYamaguchi T: Notochordal tumours in Fletcher CDMBridge JAHogendoorn PCW (eds): WHO Classification of Tumours of Soft Tissue and Boneed 4. Lyon, France: IARC Press2013 Vol 5 pp 328329

    • Search Google Scholar
    • Export Citation
  • 9

    Froehlich EVRinner BDeutsch AJMeditz KKnausz HTroppan K: Examination of survivin expression in 50 chordoma specimens—a histological and in vitro study. J Orthop Res 33:7717782015

    • Search Google Scholar
    • Export Citation
  • 10

    Howe FARobinson SPMcIntyre DJStubbs MGriffiths JR: Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours. NMR Biomed 14:4975062001

    • Search Google Scholar
    • Export Citation
  • 11

    Hug EBLoredo LNSlater JDDeVries AGrove RISchaefer RA: Proton radiation therapy for chordomas and chondrosarcomas of the skull base. J Neurosurg 91:4324391999

    • Search Google Scholar
    • Export Citation
  • 12

    Ingrisch MSchneider MJNörenberg DNegrao de Figueiredo GMaier-Hein KSuchorska B: Radiomic analysis reveals prognostic information in T1-weighted baseline magnetic resonance imaging in patients with glioblastoma. Invest Radiol 52:3603662017

    • Search Google Scholar
    • Export Citation
  • 13

    Kayani BSewell MDHanna SASaifuddin AAston WPollock R: Prognostic factors in the operative management of dedifferentiated sacral chordomas. Neurosurgery 75:2692752014

    • Search Google Scholar
    • Export Citation
  • 14

    Kim JHJung HHChang JHChang JWPark YGChang WS: Gamma Knife surgery for intracranial chordoma and chondrosarcoma: radiosurgical perspectives and treatment outcomes. J Neurosurg 121 (Suppl):1881972014

    • Search Google Scholar
    • Export Citation
  • 15

    Lee IJLee RJFahim DK: Prognostic factors and survival outcome in patients with chordoma in the United States: a population-based analysis. World Neurosurg 104:3463552017

    • Search Google Scholar
    • Export Citation
  • 16

    Ma JPTian KBWang LWang KLi DYang Y: Proposal and validation of a basic progression scoring system for patients with skull base chordoma. World Neurosurg 91:4094182016

    • Search Google Scholar
    • Export Citation
  • 17

    McMaster MLGoldstein AMBromley CMIshibe NParry DM: Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control 12:1112001

    • Search Google Scholar
    • Export Citation
  • 18

    Meng TYin HLi BLi ZXu WZhou W: Clinical features and prognostic factors of patients with chordoma in the spine: a retrospective analysis of 153 patients in a single center. Neuro Oncol 17:7257322015

    • Search Google Scholar
    • Export Citation
  • 19

    Miura THirano SNakamura TTanaka EShichinohe TTsuchikawa T: A new preoperative prognostic scoring system to predict prognosis in patients with locally advanced pancreatic body cancer who undergo distal pancreatectomy with en bloc celiac axis resection: a retrospective cohort study. Surgery 155:4574672014

    • Search Google Scholar
    • Export Citation
  • 20

    Otani RMukasa AShin MOmata MTakayanagi STanaka S: Brachyury gene copy number gain and activation of the PI3K/Akt pathway: association with upregulation of oncogenic brachyury expression in skull base chordoma. J Neurosurg 128:142814372018

    • Search Google Scholar
    • Export Citation
  • 21

    Pallini RMaira GPierconti FFalchetti MLAlvino ECimino-Reale G: Chordoma of the skull base: predictors of tumor recurrence. J Neurosurg 98:8128222003

    • Search Google Scholar
    • Export Citation
  • 22

    Park JKHodges TArko LShen MDello Iacono DMcNabb A: Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol 28:383838432010

    • Search Google Scholar
    • Export Citation
  • 23

    Preusser MWolfsberger SCzech TSlavc IBudka HHainfellner JA: Survivin expression in intracranial ependymomas and its correlation with tumor cell proliferation and patient outcome. Am J Clin Pathol 124:5435492005

    • Search Google Scholar
    • Export Citation
  • 24

    Saito TSugiyama KTakeshima YAmatya VJYamasaki FTakayasu T: Prognostic implications of the subcellular localization of survivin in glioblastomas treated with radiotherapy plus concomitant and adjuvant temozolomide. J Neurosurg 128:6796842018

    • Search Google Scholar
    • Export Citation
  • 25

    Samii AGerganov VMHerold CHayashi NNaka TMirzayan MJ: Chordomas of the skull base: surgical management and outcome. J Neurosurg 107:3193242007

    • Search Google Scholar
    • Export Citation
  • 26

    Sanhueza CWehinger SCastillo Bennett JValenzuela MOwen GIQuest AF: The twisted survivin connection to angiogenesis. Mol Cancer 14:1982015

    • Search Google Scholar
    • Export Citation
  • 27

    Sasaki TLopes MBHankins GRHelm GA: Expression of survivin, an inhibitor of apoptosis protein, in tumors of the nervous system. Acta Neuropathol 104:1051092002

    • Search Google Scholar
    • Export Citation
  • 28

    Schuetze SMBolejack VChoy EGanjoo KNStaddon APChow WA: Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor. Cancer 123:90972017

    • Search Google Scholar
    • Export Citation
  • 29

    Sheng LWan BFeng PSun JRigo FBennett CF: Downregulation of Survivin contributes to cell-cycle arrest during postnatal cardiac development in a severe spinal muscular atrophy mouse model. Hum Mol Genet 27:4864982018

    • Search Google Scholar
    • Export Citation
  • 30

    Shinmura RMatsui OKobayashi STerayama NSanada JUeda K: Cirrhotic nodules: association between MR imaging signal intensity and intranodular blood supply. Radiology 237:5125192005

    • Search Google Scholar
    • Export Citation
  • 31

    Stacchiotti SSommer J: Building a global consensus approach to chordoma: a position paper from the medical and patient community. Lancet Oncol 16:e71e832015

    • Search Google Scholar
    • Export Citation
  • 32

    Tian KWang LMa JWang KLi DDu J: MR imaging grading system for skull base chordoma. AJNR Am J Neuroradiol 38:120612112017

    • Search Google Scholar
    • Export Citation
  • 33

    Tian KZhang HMa JWang KRu XDu J: Factors for overall survival in patients with skull base chordoma: a retrospective analysis of 225 patients. World Neurosurg 97:39482017

    • Search Google Scholar
    • Export Citation
  • 34

    Uhl MMattke MWelzel TRoeder FOelmann JHabl G: Highly effective treatment of skull base chordoma with carbon ion irradiation using a raster scan technique in 155 patients: first long-term results. Cancer 120:341034172014

    • Search Google Scholar
    • Export Citation
  • 35

    Varga PPSzövérfi ZFisher CGBoriani SGokaslan ZLDekutoski MB: Surgical treatment of sacral chordoma: prognostic variables for local recurrence and overall survival. Eur Spine J 24:109211012015

    • Search Google Scholar
    • Export Citation
  • 36

    Varughese RKTorp SH: Survivin and gliomas: A literature review. Oncol Lett 12:167916862016

  • 37

    Villanueva-Meyer JEWood MDChoi BSMabray MCButowski NATihan T: MRI features and idh mutational status of grade ii diffuse gliomas: impact on diagnosis and prognosis. AJR Am J Roentgenol 210:6216282018

    • Search Google Scholar
    • Export Citation
  • 38

    Walcott BPNahed BVMohyeldin ACoumans JVKahle KTFerreira MJ: Chordoma: current concepts, management, and future directions. Lancet Oncol 13:e69e762012

    • Search Google Scholar
    • Export Citation
  • 39

    Wang LTian KWang KMa JRu XDu J: Factors for tumor progression in patients with skull base chordoma. Cancer Med 5:236823772016

    • Search Google Scholar
    • Export Citation
  • 40

    Wang LWu ZTian KWang KLi DMa J: Clinical features and surgical outcomes of patients with skull base chordoma: a retrospective analysis of 238 patients. J Neurosurg 127:125712672017

    • Search Google Scholar
    • Export Citation
  • 41

    Wasko RJankowska AWaligorska-Stachura JAndrusiewicz MJaskula MSowinski J: Survivin expression in pituitary adenomas. Neuroendocrinol Lett 26:2092122005

    • Search Google Scholar
    • Export Citation
  • 42

    Wu ZZhang JZhang LJia GTang JWang L: Prognostic factors for long-term outcome of patients with surgical resection of skull base chordomas—106 cases review in one institution. Neurosurg Rev 33:4514562010

    • Search Google Scholar
    • Export Citation
  • 43

    Yamada YKuroiwa TNakagawa TKajimoto YDohi TAzuma H: Transcriptional expression of survivin and its splice variants in brain tumors in humans. J Neurosurg 99:7387452003

    • Search Google Scholar
    • Export Citation
  • 44

    Zhao YLeng SLi DFeng SWang ZTao C: Pulmonary function impairment predicted poor prognosis of patients with hepatocellular carcinoma after hepatectomy. Oncotarget 8:75326753352017

    • Search Google Scholar
    • Export Citation
  • 45

    Zou MXLv GHZhang QSWang SFLi JWang XB: Prognostic factors in skull base chordoma: a systematic literature review and meta-analysis. World Neurosurg 109:3073272018

    • Search Google Scholar
    • Export Citation
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