Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer

Background

To investigate the prognostic significance of altered breast cancer susceptibility gene 1 (BRCA1) and p53 expression in triple-negative breast cancer (TNBC).

Methods

Immunohistochemical expression of BRCA1 and p53 was examined in the tumor tissues of 465 TNBC cases and relations were sought with clinicopathological features and patient survival.

Results

Loss of BRCA1 expression was found in 29.5% (137/465) of TNBCs. Positive expression of p53 was observed in 49.9% (232/465). Patients with loss of BRCA1 expression had a tendency to have higher rate of lymph node metastasis (p = 0.075). An association between p53 expression and high histological grade was observed (p = 0.039). TNBC patients with loss of BRCA1 expression had a tendency to have poorer overall survival (OS) than those positive for BRCA1 (p = 0.09). TNBC patients with positive p53 expression showed better OS than those with p53 negativity (p = 0.001). In terms of combined expression patterns, significantly poorer overall survival (OS) was observed for BRCA1-negative/p53-negative TNBCs and best OS for BRCA1-positive/p53-positive TNBCs (p = 0.005).

Conclusions

Combined expression patterns of BRCA1 and p53 could serve as useful prognostic markers in TNBC.

     

Stigma and Knowledge as Determinants of Recommendation and Referral Behavior of General Practitioners and Internists

Background

Despite reported effectiveness, weight loss surgery (WLS) still remains one of the least preferred options for outpatient providers, especially in Germany. The aim of this study was to examine the effect of stigma and knowledge on recommendation of WLS and referral to a surgeon by general practitioners (GPs) and internists.

Method

The sample consists of 201 GPs and internists from Germany. The questionnaire included questions on the perceived effectiveness of WLS, the frequency of recommendations of WLS, and the frequency of referral to WLS. Stigma, as well as knowledge was also assessed in this context. Linear and logistic regression models were conducted. A mediation analysis was carried out within post hoc analysis.

Results

Knowledge (b?=?0.258, p?<?0.001) and stigma towards surgery (b?=??0.129, p?=?0.013) were related to the frequency of recommendation of WLS. Additionally, respondents, who were more likely to express negative attitudes towards WLS, were less likely to recommend WLS and thus refer patients to WLS (b?=??0.107, p?<?0.05). Furthermore, respondents with more expertise on WLS were more likely to recommend and thus refer patients to WLS (b?=?0.026, p?<?0.05).

Conclusion

This study showed that stigma plays a role when it comes to defining treatment pathways for patients with obesity. The question remains how this might influence the patients and their decision regarding their treatment selection. Interventions are required to make treatment decisions by physicians or patients independent of social pressure due to stigma.

     

Role of endogenous 4-1BB in the development of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies directed against nuclear antigens including nucleosomes and DNA. To determine the role of T-cell costimulatory molecule 4-1BB in the regulation of SLE, MRL-Fas(lpr) (lpr) mice deficient in 4-1BB (lpr/4-1BB(-/-)) were generated and their disease phenotype was compared to that of control lpr mice. The main finding of this study is that the lpr/4-1BB(-/-) mice had more pronounced skin lesions which appeared earlier, increased lymphadenopathy, increased renal damage, and higher mortality than 4-1BB-intact control lpr mice. The increased severity of lesions in lpr/4-1BB(-/-) mice was closely associated with increases in CD4(+) T, CD3(+) B220(+) double-negative T cells, serum immunoglobulin, anti-dsDNA autoantibodies, and tissue immunoglobulin deposits. These data suggest that the 4-1BB-4-1BB ligand signalling pathway plays an important role in SLE and that deletion of 4-1BB confers susceptibility to lpr mice, leading to accelerated induction of disease and early mortality.