PTEN, Phospho-Akt and IGF-1 Receptor Expression in Triple Negative Breast Cancers: An Immunohistochemical Study with Outcome Correlation.
Puay Hoon H Tan, Aye Aye Thike, Poh Yian Cheok. Singapore General Hospital, Singapore
Background: Triple negative (TN) breast cancers are defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and c-erbB2 expression. Oncologic management options for this group of aggressive tumors are limited. There is a need to understand the mechanisms that propel tumor cell growth. In this study, we investigate protein expression of PTEN, a tumor suppressor gene, as well as phospho-Akt and IGF-1 receptor in a series of TN breast cancers.
Design: The cohort comprised 144 TN breast cancers diagnosed between 2005 to 2007, to which antibodies to basal markers (CK14, 34βE12, EGFR), PTEN, phospho-Akt and IGF-1 receptor were applied to sections cut from tissue microarray blocks, using the streptavidin-biotin method. Intensity and proportion of tumor cells stained were assessed. Follow-up was obtained from casenotes. DFS and OS were defined as time from diagnosis to recurrence or death respectively, and correlated with protein immunohistochemical expression using H-scores. A p value <0.05 defined statistical significance.
Results: Median age was 53 years. Majority (84%) were Chinese, 6% Malay, 6% Indian, and 4% of other ethnic origins. Tumor size ranged from 0.6 to 18 cm (mean 3.2 cm, median 2.5 cm). Infiltrative ductal carcinoma was the commonest subtype (94%). Histologic grade 3 tumors predominated (86%). Node positivity occurred in 33%. CK14, 34βE12 and EGFR confirmed 87% to be basal-like. PTEN, phospho-Akt, IGF-1 receptor were expressed in 37%, 92% and 99% of cases. There was a statistically significant association of phospho-Akt with basal-like expression (p=0.018), IGF-1 receptor staining percentage and immunoreactive score (p=0.022, p=0.007). Follow-up ranged from 5 to 67 months (mean, median 36 months). Recurrences occurred in 17% and deaths in 10% of women. DFS was significantly reduced in PTEN negative TN breast cancer using a minimum of 10% stained cells as the cutoff (p=0.011). OS was statistically diminished with IGF1-receptor expression using a H-score of 100 as the threshold (p=0.041).
Conclusions: PTEN, phospho-Akt and IGF1-receptor appear to have biological roles in TN breast cancer. Loss of PTEN expression augurs a worse DFS, which may be partly related to therapy resistance. The prognostic utility of IGF1-receptor can be harnessed as a potential treatment option using small molecule inhibitors of this receptor. Phospho-Akt correlation with basal-like expression implicates its involvement in this group of tumors and can be further interrogated to achieve effective treatment alternatives.
Monday, February 28, 2011 1:00 PM
Poster Session II # 63, Monday Afternoon