Exon 20 PIK3CA mutations decreases survival in aggressive (HER-2 positive) breast carcinomas.
PIK3CA mutations at 9 and 20 exons were studied in a series of 56 selected aggressive breast carcinomas (BC): 27 with Her-2 over-expression and negativity for estrogen receptors (ER) and progesterone receptors (PR), and 29 "triple negative" BC (negative for ER, PR and Her-2). Also, immunohistochemical studies of p53, ki-67, Her-1 (EGFR), pIGF-1R, PTEN, p110alpha, and pAkt were performed. Six mutations in exon 20 PIK3CA were identified among the 27 Her-2 positive BC, whereas only one exon 9 PIK3CA mutation was detected in a triple negative tumor (p = 0.035). Furthermore, PIK3CA mutations were associated with p110alpha over-expression (p = 0.001). Overall survival was shorter in cases with PIK3CA mutations (p = 0.015 in all series; and p = 0.041 for Her-2+ tumors), although multivariate analyses did not show statistical differences. No statistical significance was related with disease-free survival. Exon 20 PIK3CA mutations are relatively frequent in Her-2+ tumors and shorten survival, whereas neither exons 9 and 20 mutations seem related with "triple negative" breast carcinomas.
Lerma
Enrique
E
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain. elerma@santpau.es
Catasus
Lluis
L
Gallardo
Alberto
A
Peiro
Gloria
G
Alonso
Carmen
C
Aranda
Ignacio
I
Barnadas
Agusti
A
Prat
Jaime
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013030:Spain / Q000453:epidemiology
D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human