Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer

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, 195 This article is freely accessible online.

Construction of an immune-related genes nomogram for the preoperative prediction of axillary lymph node metastasis in triple-negative breast cancer,

The aim of the present study was to evaluate the expression and specific role of microRNA (miR)-142-5p in the progression of intrahepatic cholangiocarcinoma (ICC). Reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-142-5p expression in patients with ICC and healthy control subjects. The results revealed that plasma miR-142-5p was significantly increased in patients with ICC compared with the control group. Furthermore, miR-142-5p was also increased in ICC tissues compared with adjacent non-neoplastic tissues. Compared with patients with Ta-T1 stage ICC, miR-142-5p was significantly elevated in patients with ICC ≥T2 stage. Patients with ICC at G3 stage had much higher plasma miR-142-5p levels compared with those at G1/2 stage. Receiver operating characteristic analysis indicated that miR-142-5p could be used as a biomarker to differentiate patients with ICC from healthy controls. Kaplan-Meier analysis demonstrated that plasma miR-142-5p was negatively correlated with survival in patients with ICC. A dual luciferase reporter assay indicated that miR-142-5p significantly suppressed the relative luciferase activity of pmirGLO-PTEN-3' untranslated region compared with the control group. In summary, the results of the present study provide novel data indicating that plasma miR-142-5p is significantly upregulated in patients with ICC. miR-142-5p may therefore have potential as a biomarker for screening patients with ICC from healthy controls.