Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma.
BACKGROUND
We aimed to study the prevalence and prognostic influence of epidermal growth factor receptor (EGFR) and its downstream effectors in synovial sarcoma (SS).


OBJECTIVE
The tissue blocks from 30 patients were obtained. Expression of EGFR and phosphatase and tensin homolog (PTEN) were examined by immunohistochemistry, and mutation status of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2, V-raf murine sarcoma viral oncogene homolog B1 (BRAF) exon 15, phosphoinositide-3-kinase, catalytic, alpha polypeptide (PI3KCA) exons 9, 20, and PTEN exons 5-9 were analyzed by direct sequencing.


RESULTS
EGFR overexpression and PTEN deletion were found in 63.3% and 46.7% of patients. Sequence analysis failed to demonstrate mutations of KRAS and BRAF. However, an E545A point mutation in exon 9 of PI3KCA was found in 2 of the 30 (6.7%) cases and 4 point mutations in exon 5 (E99K, D106N), intro 6 to exon 7 (AATA(G)), and exon 9 (A359T) of PTEN were found in 2 of the 30 (6.7%) cases. PTEN loss was significantly more frequent in cases of trunk tumors, and the overexpression of EGFR was significantly more prevalent in patients who were 35 or older.


CONCLUSIONS
PTEN deletion was associated with poor survival.
Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Hao-Wei
HW
Teng
Hsei-Wei
HW
Wang
Wei-Ming
WM
Chen
Ta-Chung
TC
Chao
Yao-Yu
YY
Hsieh
Chi-Hsiu
CH
Hsih
Cheng-Hwai
CH
Tzeng
Paul Chih-Hsueh
PC
Chen
Chueh-Chuan
CC
Yen
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D015995:Prevalence; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D013584:Sarcoma, Synovial / Q000378:metabolism* / Q000401:mortality*; D020539:Sequence Analysis, Protein; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality*; D016019:Survival Analysis; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins