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Trento, Italy

Cuorvo L.V.,Laboratory of Molecular Pathology | Verderio P.,Unit of Medical Statistics | Ciniselli C.M.,Unit of Medical Statistics | Girlando S.,Unit of Surgical Pathology | And 18 more authors.
Virchows Archiv | Year: 2014

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. © 2013 Springer-Verlag Berlin Heidelberg.


Barbareschi M.,Laboratory of Molecular Pathology | Cuorvo L.V.,Laboratory of Molecular Pathology | Girlando S.,Laboratory of Molecular Pathology | Bragantini E.,Laboratory of Molecular Pathology | And 9 more authors.
Virchows Archiv | Year: 2012

The purpose of this study is to evaluate whether activating mutations of the p110α catalytic subunit of class A phosphoinositide 3-kinases (PI3KCA) or complete loss of phosphatase and tensin homolog (PTEN) is associated with response to anti-human epidermal growth factor receptor 2 (Her2) treatment in breast cancer (BC). We analysed PI3KCA hot-spot mutations and PTEN immunohistochemical expression in 129 Her2-positive infiltrating BC treated with trastuzumab, including 26 cases treated with neoadjuvant therapy, 48 metastatic infiltrating breast cancer (IBC; MBC) and 55 early-stage IBC, with complete clinical information (mean follow-up 37, 66 and 32 months, respectively). PI3KCA hot-spot mutationswere observed in 25 cases (19%):12 (9 %) in exon 9 and 13 (10 %) in exon 20. No correlations were observed between mutations and pathological and biological parameters. In patients treated with neoadjuvant therapy and in MBC, we did not observe any relationship with response to trastuzumab-based therapy. PTEN loss was observed in 24 out of 86 informative cases (28 %), 3 (13 %) of which were also mutated for PI3KCA. PI3K pathway activation, defined as PI3KCA mutation and/or PTEN loss, was not associated with response to treatment or clinical outcome in MBC. PI3KCA mutation and/or PTEN loss should not exclude patients from potentially beneficial anti-Her2 therapy. © Springer-Verlag 2012.

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