Differences in AKT Pathway Detected by Digital Quantification of Protein Expression in Different Subtypes of Breast Cancer
JVS Carniello, RM Rocha, FA Soares, VP Andrade. AC Camargo Cancer Hospital, Sao Paulo, SP, Brazil
Background: AKT pathway is involved in breast cancer progression and differential expression among molecular subtypes of breast cancer has been described. Some new modulators of AKT pathway are under investigation for clinical treatment and quantification at the protein level may be clinically relevant. So far no standard method to quantify the AKT pathway is available.
Design: We evaluated protein expression by immunohistochemistry of AKT, pAKT, mTOR, PTEN, ER, PR and Her2 performed using Tissue microarrays including 56 breast carcinomas, T1/T2 without metastasis in patients between 40 and 70 years old using tissue microarray. Cases where classified based on the expression of estrogen receptor and Her2. The digital quantification was performed using the ACIS III microscope. Local invasion and proliferation parameters were compared to the molecular profile and AKT, pAKT, mTOR and PTEN levels of expression.
Results: The mean age was 53 and the mean tumor size was 2.65 cm (0.4 to 4.5 cm). The mean cytoplasmic expressions were AKT=109.74, pAKT=86.21, mTOR=96.85 and PTEN=121.01. Nuclear staining was observed in 18 (36.0%), 23 (46%), 0 (0%) and 29 (56.7%) cases of AKT, pAKT, mTOR and PTEN, respectively. Triple negative tumors were associated with high mitotic index (p=0.036), low cytoplasmic expressions of AKT and mTOR (p=0.027 and p=0.037, respectively). There was no association between AKT, pAKT, mTOR or PTEN expression and tumor size, number of mitosis or mitotic index. We observed a positive and significant correlation between the expression of PTEN and AKT (r = 0.40; p = 0,003); PTEN and pAKT (r = 0.32; p = 0.012); but no correlation between PTEN and mTOR (r = 0.06; p = 0.76).
Conclusions: Triple Negative tumors showed lower cytoplasmic expression of AKT and mTOR compared to Luminal A tumors. The high mitotic index observed in triple negative tumors was not associated to AKT pathway overexpression. The digital quantification using immunohistochemistry can detect differences in protein expression of AKT pathway among breast cancer molecular subtypes and may be of clinical use.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 53, Tuesday Morning