PI3KCA mutation status is of limited prognostic relevance in ER-positive breast cancer patients treated with hormone therapy.
PI3K/AKT/mTOR pathway alterations are frequent in patients with infiltrating breast cancer (IBC). Their clinical and pathological relevance has been insufficiently documented. We evaluated PI3KCA for mutations and the expression of PTEN, AKT, mTOR and p70S6K by immunohistochemistry in 246 IBC patients treated with hormone therapy (median follow-up, 97 months). A PI3KCA mutation was observed in 50 out of 229 informative cases (21.8 %), PTEN loss in 107 out of 210 (51 %), moderate/high level of expression of AKT in 133 out of 188 (71 %), moderate/high level of expression of mTOR in 173 out of 218 (79 %) and moderate/high level of expression of p70S6K in 111 out of 192 cases (58 %). PI3KCA mutation was associated with the absence of Her2/neu amplification/overexpression and a low level of MIB1/Ki-67 labelling. The expression of p70S6K was associated with a high level of mTOR immunoreactivity, and high PTEN expression was associated with high AKT expression level. Univariate analysis showed that PI3KCA mutation status was not associated with clinical outcome in the series as a whole or in the node-negative subgroup. However, in the node-positive subgroup, exon 9 PI3KCA mutation was associated with unfavourable overall survival (OS), although its impact on the final model in multivariate analysis seemed to be limited. Of the other markers, only high p70S6K expression was associated with a significantly prolonged OS. PI3KCA mutation status is of limited prognostic relevance in oestrogen receptor-positive breast cancer patients treated with hormone therapy.
Lucia Veronica
LV
Cuorvo
Paolo
P
Verderio
Chiara Maura
CM
Ciniselli
Salvatore
S
Girlando
Nicola
N
Decarli
Elena
E
Leonardi
Antonella
A
Ferro
Alessia
A
Caldara
Renza
R
Triolo
Claudio
C
Eccher
Chiara
C
Cantaloni
Francesco
F
Mauri
Michael
M
Seckl
Marco
M
Volante
Fiamma
F
Buttitta
Antonio
A
Marchetti
Quattrone
Q
Silvia
Enzo
E
Galligioni
Paolo Dalla
PD
Palma
Mattia
M
Barbareschi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000032:analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis; D058570:TOR Serine-Threonine Kinases / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*
D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human