Immunohistochemical study of PTEN and phosphorylated mTOR proteins in familial and sporadic invasive breast carcinomas.
OBJECTIVE
Loss of phosphatase and tensin homologue (PTEN) leads to activation of several kinases, including mammalian target of rapamycin (mTOR), which promotes cell cycle progression. The aim was to study the expression of PTEN and phosphorylated (p)-mTOR in familial and sporadic invasive breast carcinomas and their relation to clinicopathological features, molecular indices (Wnt1) and patients' survival.


RESULTS
PTEN and p-mTOR were detected immunohistochemically in 215 sections of invasive breast carcinomas (112 with a familial history of breast cancer). Image analysis was used and univariate and multivariate analyses employed for statistical evaluation of results. PTEN was detected in the nucleus (73.5%) and p-mTOR in the cytoplasm (44.2%) of cancer cells. Loss of PTEN protein was more frequently detected in women with a familial history of breast cancer (72%) (P < 0.0001), while its expression was negatively correlated with Wnt1, in total (P = 0.049). p-mTOR showed a positive association with lymph node status (P = 0.010) and was found to have a negative impact on patients' overall survival (P = 0.016).


CONCLUSIONS
Loss of PTEN protein expression appears to occur more frequently in women with a family history of breast cancer, whereas activation of mTOR protein seems to be related to a more aggressive phenotype.
Bakarakos
Panagiotis
P
1st Department of Pathology, Medical School, University of Athens, Athens, Greece.
Theohari
Irene
I
Nomikos
Alexandros
A
Mylona
Eleni
E
Papadimitriou
Christos
C
Dimopoulos
Athanasios-Meletios
AM
Nakopoulou
Lydia
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase