Aims Progesterone receptor (PR) expression is prognostic in early stage breast cancer. There are several reports of discordant expression between primary tumour and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER) and PR. We sought to determine whether expression of these biomarkers in the synchronous ALN metastases of ER positive (+), HER2 negative (−) breast cancer could provide more accurate prognostic information.

Methods The retrospective cohort included 229 patients from a single institution with ER+, HER2− breast cancer who had synchronous ALN metastatic disease (2005–2014). PR expression was correlated with relapse-free survival, and subset analysis was performed for patients who received adjuvant tamoxifen or an aromatase inhibitor.

Results One patient had an ER+ primary tumour, which was ER− in the ALN metastasis. 27 (11.3%) were PR− in the primary tumour and 56 (23.6%) in the ALN metastasis. The predominant change was from PR+ in the primary tumour to PR− in the lymph node. Absence of PR expression in the ALN was significantly associated with relapse; however, this was not the case in the primary tumour. In a subset analysis of patients taking adjuvant endocrine therapy, poorer prognosis was limited to those with PR− metastases on tamoxifen (HR=5.203, 95% CI 1.649 to 16.416, p=0.005). No significant prognostic effect of PR− metastases in patients taking aromatase inhibitors was seen (HR=1.519, 95% CI 0.675 to 3.418, p=0.312).

Conclusions Evaluation of PR expression in ALN metastasis may enable prediction of patients who are less likely to benefit from adjuvant tamoxifen. This study should be replicated in other cohorts.

Introduction: NSCLC is the leading cause for cancer-related deaths worldwide. New therapeutic targets are needed, as development of resistance to current treatment, such as platinum-based chemotherapy, is inevitable. The purpose of this study was to determine the functional relevance and therapeutic potential of cell division cycle associated 3 protein (CDCA3) in NSCLC.

Methods: The expression of CDCA3 in squamous and nonsquamous NSCLC was investigated by using bioinformatics, Western blot analysis of matched tumor and normal tissue, and immunohistochemistry of a tissue microarray. The function of CDCA3 in NSCLC was determined by using several in vitro assays with small interfering RNA depleting CDCA3 in a panel of three immortalized human bronchial epithelial cell (HBEC) lines and seven NSCLC cell lines.

Results: In this study, cell division cycle associated 3 gene (CDCA3) transcripts were identified as highly increased in NSCLC versus in nonmalignant tissue, with high levels of CDCA3 being associated with poor patient prognosis. CDCA3 protein was also increased in NSCLC tissue and expression was limited to tumor cells. CDCA3 expression was similarly increased in a panel of NSCLC cell lines compared with in three HBEC lines. Although depletion of CDCA3 in the HBEC lines did not affect cellular proliferation, depletion of CDCA3 expression markedly reduced the proliferation of all NSCLC cell lines. CDCA3 depletion caused a defective G2/M-phase cell cycle progression, upregulation of p21 independent of p53, and induction of cellular senescence.

Conclusions: Our findings highlight CDCA3 as a prognostic factor and potential novel therapeutic target in NSCLC through inhibition of tumor growth and promotion of tumor senescence.