Dual PTEN and RB Loss Predict Invasive Recurrence of DCIS
Rebecca L Lipinski, Ray W O'Neill, Erik S Knudsen, Gordon F Schwartz, Agnieszka K Witkiewicz. Thomas Jefferson University, Philadelphia, PA
Background: Currently there is paucity of markers allowing to predict which DCIS lesions will recur as an invasive disease. The RB tumor suppressor pathway is an important regulator of cell proliferation that has been shown to become functionally lost in close to 30% of DCIS. Loss of RB is associated with increased risk of DCIS progression to invasive breast cancer. PTEN is a tumor suppressor gene that is frequently altered in advanced breast cancers. Loss of PTEN expression has been associated with breast cancer metastasis and death in previous studies but its role in DCIS progression has not been investigated. It has previously been shown that loss of PTEN may be related to RB pathway inactivation through its effects on cyclin D1.
The goal of this study was to elucidate the potential role of RB and PTEN as predictive biomarkers for recurring breast cancer disease.
Design: 230 DCIS patients treated with surgery and clinical follow up were included in the study. Expression of PTEN and RB was assessed by employing a standard immunoperoxidase method with primary PTEN antibody (Cell Signaling Technologies, Rabbit Monoclonal, 138G6, 1:100) and primary RB antibody, (Thermoscientific; catalog no. MS-107-B, 1:50). PTEN expression was scored semi-quantitatively as negative (cancer cells showed no staining while normal cells were positive), weak (staining intensity was less than adjacent normal cells), or strong (staining intensity was equal to adjacent normal cells). PTEN loss was defined as a score of either negative, or weak. RB expression was scored as negative or positive (any neoplastic cell staining). Association between markers expression and recurrence was assessed using Kaplan-Meier Survival Analysis.
Results: Of the 230 DCIS cases, 68 (29%) recurred (46 as DCIS and 22 as invasive carcinoma). There was a statistically significant association between loss of RB expression and invasive recurrence (p=.0014). However, its significance was increased when considered in combination with PTEN loss (p<.0001). An invasive recurrence was observed in 41% of patients with RB/PTEN loss, while 6% of patients with no recurrence showed RB/PTEN loss of expression.
Conclusions: Dual PTEN and RB expression loss in DCIS is associated with increased risk of invasive breast cancer recurrence. The combination of PTEN and RB may prove useful as predictive biomarkers for invasive breast cancer recurrence.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 24, Tuesday Morning