Prognostication of soft tissue sarcomas based on chromosome 17q gene and protein status: evaluation of TOP2A, HER-2/neu, and survivin.
BACKGROUND
Topoisomerase 2 alpha (TOP2A), HER-2/neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors. In a previous study, we showed that TOP2A transcripts levels were significantly higher in soft tissue sarcomas (STS) than in benign tumors and desmoid-type fibromatoses (FM). Because these genes have been insufficiently examined in STS, we aimed to identify alterations in TOP2A and HER-2 expression by fluorescent in situ hybridization and immunohistochemistry, as well as that of survivin, and correlate them with clinicopathologic findings to assess their prognostic value.


METHODS
Eighteen FM and 244 STS were included. Fluorescent in situ hybridization and immunohistochemistry were performed on a tissue microarray.


RESULTS
TOP2A and survivin were more highly expressed in sarcomas than in FM. TOP2A was an independent predictor of an unfavorable prognosis; it was combined with formerly established prognostic factors (primarily histologic grade and tumor size at diagnosis) to create a prognostic index that evaluated overall survival. Gene amplification/polysomy (13%) did not correlate with protein overexpression. Survivin and HER-2 expression were not associated with patient outcomes.


CONCLUSIONS
These findings might become valuable in the management of patients with STS and possibly in the prospective evaluation of responses to new target-driven therapies.
Hospital do Câncer A. C. Camargo, Fundação Antonio Prudente, São Paulo, Brazil.
Isabela Werneck
IW
da Cunha
Louise
L
De Brot
Kátia Cândido
KC
Carvalho
Rafael Malagoli
RM
Rocha
José Humberto
JH
Fregnani
Roberto
R
Falzoni
Fábio de Oliveira
Fde O
Ferreira
Samuel
S
Aguiar
Ademar
A
Lopes
Nair Hideko
NH
Muto
Luiz F L
LF
Reis
Fernando Augusto
FA
Soares
José
J
Vassallo
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005350:Fibroma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018222:Desmoid Tumors / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012509:Sarcoma / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D013584:Sarcoma, Synovial / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D000077022:Survivin; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077022:Survivin; C107489:BIRC5 protein, human; C508053:ERBB2 protein, human; C000618811:TOP2A protein, human