The prognostic value of Ki-67, p53, epidermal growth factor receptor, 1p36, 9p21, 10q23, and 17p13 in skull base chordomas.
BACKGROUND
Skull base chordomas are rare, locally aggressive, notochord-derived neoplasms for which prognostically relevant biomarkers are not well established.


OBJECTIVE
To evaluate whether newly discovered molecular alterations in chordomas have prognostic significance similar to what has been described regarding Ki-67 proliferation index.


METHODS
We conducted a retrospective study of 28 cases of primary clival chordomas.


RESULTS
Ki-67 proliferation index 5% or more, p53 accumulation, and epidermal growth factor receptor expression were seen in 32%, 44%, and 8% of chordomas, respectively. 1p loss of heterozygosity (LOH) and/or 1p36 hemizygous deletion was seen in 30% of tumors, while 9p LOH and/or 9p21 homozygous deletion was seen in 21% of cases. Loss of heterozygosity at 10q23 and 17p13 were identified in 57% and 52% of cases, respectively. Ki-67 proliferation index 5% or more and 9p LOH were significantly associated with a shorter overall survival, while homozygous deletion at 9p21 via fluorescence in situ hybridization approached significance. No correlation with survival was found for p53 or epidermal growth factor receptor expression, 1p36 hemizygous deletion, or LOH at 1p, 10q23, or 17p13.


CONCLUSIONS
Chordomas with elevated Ki-67 proliferation index or deletion at 9p21 may be at risk for a more aggressive clinical course and shorter survival. These biomarkers may thus be used to improve therapeutic stratification.
Horbinski
Craig
C
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Oakley
Gerard J
GJ
Cieply
Kathleen
K
Mantha
Geeta S
GS
Nikiforova
Marina N
MN
Dacic
Sanja
S
Seethala
Raja R
RR
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D002648:Child; D002817:Chordoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D002906:Chromosomes, Human, 6-12 and X / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D019292:Skull Base Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors