S100P as a marker for poor survival and advanced stage in gallbladder carcinoma

AimsGallbladder carcinomas usually present in advanced stages and has a dismal prognosis despite modern imaging techniques and aggressive surgical intervention. Identification of biologic markers for early diagnosis and improved therapeutic strategies is thus of paramount importance. S100P has been identified in a variety of malignant neoplasms of the gastrointestinal and pancreaticobiliary systems, but it is not yet known if S100P expression is associated with clinically-relevant characteristics of gall bladder carcinoma. The aims of the present study were: 1) to investigate the relationship between S100P expression and histological type, grade, tumor-node-metastasis stage, presence of vascular invasion, perineural invasion and necrosis; and 2) to evaluate for any S100P-defined difference in the risk for tumor recurrence or death.MethodImmunostains for S100P were performed on 4 tissue microarray blocks containing 91 cases of gall bladder carcinoma.ResultThe intensity of S100P staining was significantly associated with pathological T stage 4 (p = 0. 0238). Staining intensity ≥3 in ≥25% tumor cells was associated with pathological T stage 4 (p = 0.0005). A higher S100P immunoreactivity score (IRS) was significantly associated with higher TNM stage (p = 0.0341). Age (p = 0.0485), presence of vascular invasion (p = 0.0359), pathological T stage (p = 0.0291) and TNM stage (p = 0.0153) were significantly associated with tumor recurrence. Intense S100P reactivity was associated with decreased overall survival [hazard ratio = 9.614; 95% confidence interval (CI), 1.873–49.338; p = 0.0067].ConclusionOur findings indicate that S100P over-expression is a potential prognostic marker for gall bladder carcinoma and is significantly associated with advanced tumor stage and poorer survival.     

Complications,risk factors,and patients-reported outcomes after skin-sparing mastectomy followed by breast reconstruction in women with BRCA mutations

Background: Women with a BRCA mutation have the option of undergoing prophylactic mastectomy and immediate breast reconstruction; however, the potential negative effects of reconstruction on women’s physical and psychological well-being are unclear. This study aimed to investigate complications, patient-reported pain, health-related quality-of-life (HRQoL) and satisfaction following reconstructive surgery at Oslo University Hospital between 2006 and 2013.

Methods: Data were collected retrospectively from the records of 238 patients. A cross-sectional survey was conducted to collect patient-reported HRQoL and satisfaction with outcome using the Short Form-12 questionnaires and Breast-Q. The self-administered Leeds assessment of neuropathic symptoms and signs was used to assess neuropathic pain.

Results: The majority of participants (89.5%) underwent implant-based breast reconstruction (IBBR); the remainder underwent autologous-tissue breast reconstruction (ATBR). Overall, 28.6% had complications within 30?days of surgery and 14.6% required resurgery because of complications. Women who underwent IBBR had a later onset of complications than those undergoing ATBR. Participants in the survey (n?=?175 of 219, response rate 79.9%) reported similar HRQoL to an age-matched general female population. Few (2.9%) reported neuropathic pain. Patients who underwent IBBR were significantly less satisfied with the reconstructed breast (p?=?.001) and overall outcome (p?=?.02) than those who underwent ATBR, but there were no significant differences in HRQoL scores between the two groups.

Conclusions: Overall, 28.6% of the women had complications within 30?days and 14.6% needed resurgery. Few had neuropathic pain. Women who underwent ATBR were more satisfied with the overall outcome than those who underwent IBBR.     

Peroperative scoring systems for predicting the outcome of cytoreductive surgery in advanced-stage ovarian cancer – A systematic review

The extent of peritoneal metastases (PM) largely determines the possibility of complete or optimal cytoreductive surgery in advanced ovarian cancer. An objective scoring system to quantify the extent of PM can help clinicians to decide whether or not to embark on CRS. Therefore several scoring systems have been developed by different research teams and this review summarizes their performance in predicting a complete or optimal cytoreduction in patients with advanced ovarian cancer. A systematic search in the MEDLINE database revealed 19 articles that described a total of five main scoring systems to predict the completeness of CRS in patients with FIGO stage III-IV ovarian cancer based on the surgical exploration of the abdominal cavity; PCI, PIV, Eisenkop, Espada, and Kasper. The Peritoneal Cancer Index (PCI) and the Predictive Index Value (PIV) were mentioned most frequently and showed AUCs of 0.69–0.92 and 0.66–0.98, respectively. Due to the use of different cut-offs sensitivities and specificities greatly varied. Therefore with the current data, no scoring system could be identified as best. An objective measure of the extent of disease can be of great clinical use for identifying ovarian cancer patients for which a complete (or optimal) CRS is achievable, however due to local differences in treatment strategies and surgical policy a widely adopted objective scoring system with a standard cut-off value is not feasible. Nevertheless, objective scoring systems can play an important role to guide treatment decisions.     

Association between the NBS1 Glu185Gln polymorphism and breast cancer risk: a meta-analysis

Nijmegen breakage syndrome 1 (NBS1), a vital DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint, plays a critical role in cellular response to DNA damages and the maintenance of genomic stability. The NBS1 Glu185Gln (NBS1 E185Q, NBS1 8360G>C, rs1805794) polymorphism has been indicated to be involved in the development of cancer, but results of previous individual studies on the association between NBS1 Glu185Gln polymorphism and breast cancer risk remain controversial and inconclusive. Our meta-analysis investigated this association for the first time by pooling the odds ratios with corresponding 95 % confidence intervals (95 % CIs) of all individual publications available to date. Overall, 14 separate studies with 6,642 cases and 7,138 controls were finally included into the present meta-analysis after a comprehensive literature search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to October 21, 2012. Overall analysis and subgroup analyses by ethnicity and source of controls were performed. Meta-analysis of total studies showed that the NBS1 Glu185Gln variant carriers were not susceptible to breast cancer (OR_{Gln vs. Glu}?=?1.05, 95 % CI 0.80–1.39, P _OR?=?0.719; OR _{Gln/Gln vs. Glu/Glu}?=?0.82, 95 % CI 0.62–1.08, P _OR?=?0.154; OR _{Glu/Gln vs. Glu/Glu}?=?1.00, 95 % CI 0.90–1.13, P _OR?=?0.939; OR_{Gln/Gln + Glu/Gln vs. Glu/Glu}?=?0.96, 95 % CI 0.83–1.11, P _OR?=?0.551; OR_{Gln/Gln vs. Glu/Glu + Glu/Gln}?=?0.84, 95 % CI 0.67–1.05, P _OR?=?0.134). Similar results were observed in heterogeneity-adjusted meta-analysis of all studies. Furthermore, subgroup analyses by ethnicity and source of controls did not identify any appreciable relationship of the NBS1 Glu185Gln polymorphism with breast cancer susceptibility in any populations. Sensitivity analysis by sequentially omitting individual studies confirmed the stability and reliability of our results. Our meta-analysis of currently available data shows no association between the NBS1 Glu185Gln polymorphism and breast cancer risk.     

Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial

BackgroundCD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials.Patients and methodsFull-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival (DFS), overall survival (OS) and the extent of tumor immune infiltration.ResultsOur results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced DFS, OS and negatively correlated with tumor immune infiltration (Spearman’s R= −0.50, P < 0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome.ConclusionsTaken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human TNBC and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this BC subtype.     

Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

AimSeveral prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC.MethodsCentral pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed.ResultsMedian follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus.ConclusionsHistologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients.