Τίτλος:
Opposite Prognostic Impact of Single PTEN-loss and PIK3CA Mutations in Early High-risk Breast Cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background/Aim: PTEN-loss and PIK3CA mutations have been addressed as markers of PI3K activation in breast cancer. We evaluated these markers in early high-risk breast cancer (EBC) focusing on PTEN immunohistochemistry (IHC) issues, particularly in HER2-positive disease. Materials and Methods: We examined PTEN-loss and PIK3CA mutations in 1265 EBC patients treated with adjuvant chemotherapy within two clinical trials. Two different methods for the evaluation of PTEN IHC were used, one upfront binary (loss; no-loss) and the other initially multi-scale allowing for the classification of “grey zone” tumors with low and very low PTEN protein expression. Results: PTEN-loss (33.4% and 22.1%, depending on the IHC method) and PIK3CA mutations (29.6%) were associated with ER/PgR/HER2-negative and ER/PgR-positive disease, respectively. Concordance of the two IHC methods was moderate (Cohen’s kappa 0.624). PTEN-loss discrepancy and intra-tumor heterogeneity concerned “grey zone” tumors that were prevalent among HER2-positive cancers. PTEN-loss independently conferred higher risk for relapse and death. Compared to single PIK3CA mutations, single PTEN-loss was independently associated with increased risk for relapse and death. Depending on the evaluation method, in HER2-positive cancer, PTEN-loss was without- or of marginal unfavorable prognostic significance. Conclusion: In EBC, PTEN-loss is an independent predictor of poor outcome. When occurring singly, PTEN-loss and PIK3CA mutations have opposite prognostic impact. In HER2-positive disease, assessment of PTEN-loss by IHC appears unreliable and the marker is without clear prognostic significance. © 2019 International Institute of Anticancer Research. All rights reserved.
Συγγραφείς:
Lazaridis, G.
Kotoula, V.
Vrettou, E.
Kostopoulos, I.
Manousou, K.
Papadopoulou, K.
Giannoulatou, E.
Bobos, M.
Sotiropoulou, M.
Pentheroudakis, G.
Efstratiou, I.
Papoudou-Bai, A.
Psyrri, A.
Christodoulou, C.
Gogas, H.
Koutras, A.
Timotheadou, E.
Pectasides, D.
Zagouri, F.
Fountzilas, G.
Περιοδικό:
Cancer Genomics and Proteomics
Εκδότης:
International Institute of Anticancer Research
Λέξεις-κλειδιά:
anthracycline derivative; epidermal growth factor receptor 2; estrogen receptor; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; progesterone receptor; taxane derivative; trastuzumab; tumor marker; antineoplastic agent; epidermal growth factor receptor 2; ERBB2 protein, human; estrogen receptor; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; phosphatidylinositol 4,5 bisphosphate 3 kinase; PIK3CA protein, human; progesterone receptor; PTEN protein, human; tumor marker, adjuvant chemotherapy; adult; Article; breast cancer; cancer prognosis; cancer recurrence; cohort analysis; early cancer; estrogen receptor positive breast cancer; evaluation study; female; gene loss; gene mutation; high risk patient; human; human epidermal growth factor receptor 2 positive breast cancer; human tissue; immunohistochemistry; luminal A breast cancer; luminal B breast cancer; major clinical study; modified radical mastectomy; oncogene; partial mastectomy; pik3ca gene; progesterone receptor positive breast cancer; protein expression; risk assessment; triple negative breast cancer; breast tumor; follow up; genetics; lobular carcinoma; metabolism; middle aged; mutation; Paget nipple disease; pathology; prognosis; survival rate; tumor recurrence, Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Class I Phosphatidylinositol 3-Kinases; Cohort Studies; Female; Follow-Up Studies; Humans; Middle Aged; Mutation; Neoplasm Recurrence, Local; Prognosis; PTEN Phosphohydrolase; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Rate
