The expression of epidermal growth factor receptor and its downstream signaling molecules in osteosarcoma.
The value of epidermal growth factor receptor (EGFR) and its downstream signaling molecules as prognostic factors have been studied in many tumor types. The aim of this study was to investigate whether these molecules have prognostic value in osteosarcoma. We evaluated the immunostaining of EGFR and its downstream signaling molecules, p-EGFR, Akt, Stat-3, survivin and Erk in 47 osteosarcomas. In addition, three osteosarcoma cell lines were used to evaluate EGFR expression levels and mutation status by real-time PCR and nucleotide sequence analysis. Using tissue microarray of samples from 47 paraffin-embedded osteosarcoma cases, 26, 17, 20 and 12 cases showed positive immunostaining of EGFR, Stat-3, survivin and Erk, respectively. Survivin and Erk were statistically correlated with survival (p=0.005 and p=0.002, respectively, log-rank test). Furthermore, we found that EGFR expression was correlated with Erk expression. In addition, we also observed a significant association of survivin expression with Stat-3 and Erk activation (p=0.006 and p=0.000, Fisher's exact test). p-EGFR and Akt immunostaining were not detected in any of the cases. Two out of three osteosarcoma cell lines showed increased EGFR levels as detected by real-time PCR. One of these cell lines had a CAA to CAG mutation at exon 20 of the amplified EGFR gene, but this did not change the amino acid sequence. These results support the idea that Erk is a downstream signaling molecule of EGFR. Moreover, our data indicate that survivin and Erk could be used as prognostic factors in patients with osteosarcoma.
Do
Sung-Im
SI
Department of Pathology, School of Medicine, Kyung-Hee University, Seoul, Korea.
Jung
Woon Won
WW
Kim
Hyun Sook
HS
Park
Yong-Koo
YK
D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002648:Child; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000235:genetics; D012516:Osteosarcoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D000077022:Survivin; D055815:Young Adult
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases