The Role of IGF1R and PTEN/Akt Pathway in Young Patients with Breast Carcinoma According to Immunophenotypes
M Planelles, FI Aranda, E Alcaraz, M Niveiro, J Segui, G Peiro. University General Hospital of Alicante, Alicante, Spain
Background: Breast carcinoma (BC) in women aged 40 years or younger differs in many significant ways from those arising in older patients. Stratification of BC in immunophenotypes has shown different survival of these patients. However, the relevance of growth factor receptors and tumor suppressor genes such as IGF1R (Insulin-like growth factor 1-receptor) and PTEN, and their correlation with the Akt/Bad/mTOR pathway have not been extensively studied in this subset of patients.
Design: Formalin-fixed paraffin-embedded tissue from 146 BC in women <40 years were retrieved from the archives of the Department of Pathology at the General Hospital of Alicante (Spain). Two 1mm cores were taken from separate areas of each tumor. Four tissue microarray blocks were created. Immunohistochemistry for hormone receptors (ER/PR), HER2, Ki67, HER1, CK5/6, IGF1R, PTEN, phospho-Akt (Ser473), phospho-BAD (Ser136) and phospho-mTOR (Ser2448) were performed. Tumors were classified as (a) Luminal A (RE/RP+; HER2-; Ki67<20%); (b) Luminal B (RE/RP+; HER2-; Ki67 >20%); (c) HER2+; (d) Basal-like (ER/PR/HER2-; CK5/6 and/or HER1+). Significant associations were identified using Chi-square and Fishers exact test. Survival was calculated by the Kaplan-Meier method (log rank test). P value < 0.05 was considered significant.
Results: Mean age of the patients was 35 years (range 20-40 years). The distribution of immunophenotypes was as follows: 45 (30.8%) tumors were classified as Luminal A, 40 (27.4%) as Luminal B, 29 (19.9%) were HER2+ and 32 (21.9%) Basal-like. Luminal A tumors showed PTEN expression preserved (92%; p<0.000) and IGF1R overexpression (82%; p<0.000). In contrast, the Basal-like group showed more frequently loss of PTEN (21%; p<0.000), lower levels of IGF1R (68%; p<0.000) and also a trend towards an association with increased p-Bad (95%; p=0.19) and p-mTOR (53%; p=0.11). However, no significant association was found with the levels of p-Akt (p=ns). Among subtypes, better survival was observed for those patients with tumors with increased IGF1R (p=0.031) or preserved PTEN (p=0.05).
Conclusions: In our series of BC in young patients (<40 years) Luminal A is the most frequent immunophenotype containing increased expression of IGF1R and PTEN present, which in turn confer better prognosis. On the contrary, in Basal-like tumors, low IGF1R or loss of PTEN imply shorter patients' survival. Supported by grant FIS 06/1495.
Monday, March 9, 2009 1:00 PM
Poster Session II # 28, Monday Afternoon