Inflammatory breast cancer (IBC) represents the most aggressive presentation of breast cancer. Women diagnosed with IBC typically have a poorer prognosis compared with those diagnosed with non-IBC ...tumors. Recommendations and guidelines published to date on the diagnosis, management, and follow-up of women with breast cancer have focused primarily on non-IBC tumors. Establishing a minimum standard for clinical diagnosis and treatment of IBC is needed.
Recognizing IBC to be a distinct entity, a group of international experts met in December 2008 at the First International Conference on Inflammatory Breast Cancer to develop guidelines for the management of IBC.
The panel of leading IBC experts formed a consensus on the minimum requirements to accurately diagnose IBC, supported by pathological confirmation. In addition, the panel emphasized a multimodality approach of systemic chemotherapy, surgery, and radiation therapy.
The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.
Molecular characterisation of single circulating tumour cells (CTCs) holds considerable promise for predictive biomarker assessment and to explore CTC heterogeneity. We evaluate a new method, the ...DEPArray system, that allows the dielectrophoretic manipulation and isolation of single and 100% purified groups of CTCs from pre-enriched blood samples and explore the feasibility of their molecular characterisation.
Samples containing known numbers of two cell populations were used to assess cell loss during sample loading. Cultured breast cancer cells were isolated from spiked blood samples using CellSearch CTC and Profile kits. Single tumour cells and groups of up to 10 tumour cells were recovered with the DEPArray system and subjected to transcriptional and mutation analysis.
On average, 40% cell loss was observed when loading samples to the DEPArray system. Expected mutations in clinically relevant markers could be obtained for 60% of single recovered tumour cells and all groups of tumour cells. Reliable gene expression profiles were obtained from single cells and groups of up to 10 cells for 2 out of 3 spiked breast cancer cell lines.
We describe a semiautomated workflow for the isolation of small groups of 1 to 10 tumour cells from whole blood samples and provide proof of principle for the feasibility of their comprehensive molecular characterisation.
The High‐Dynamic Double‐Crystal Monochromator (HD‐DCM) is a mechatronic system with unique control‐based architecture and deep paradigm changes as compared with traditional beamline monochromators. ...Aiming at unprecedented inter‐crystal positioning stability in vertical‐bounce double‐crystal monochromators (DCMs) of the order of 10 nrad RMS (1 Hz to 2.5 kHz), and not only in fixed‐energy but also in fly‐scan operation, it has been developed according to a `first‐time right' predictive design approach for hard X‐ray beamlines at Sirius, the fourth‐generation light source at the Brazilian Synchrotron Light Laboratory (LNLS/CNPEM). This work explores some of the challenges that emerge with this new technology and presents the latest commissioning results that demonstrate the unparallel performances of the HD‐DCM at the undulator‐based EMA (Extreme Methods of Analysis) beamline at Sirius. With the enabled fast spectroscopy fly‐scan possibilities, a new energy‐tuning evaluation method, based on wave‐propagation simulations, becomes part of a motion‐oriented analysis that is carried out to derive the multi‐axis non‐linear positioning problem, covering not only energy selection and fixed exit in the HD‐DCM but also the emission spectrum of an adjustable‐phase undulator (APU). The HD‐DCM control scheme and its flexible operation modes are described in detail as well. Furthermore, a new integration topology between the HD‐DCM and EMA's APU, coming already close to ultimate motion levels, is described and validated.
The High‐Dynamic Double‐Crystal Monochromator that has been developed for the fourth‐generation light source Sirius/LNLS is explored, with its unprecedented inter‐crystal stability performance around 10 nrad RMS both at fixed‐energy and continuous fly‐scan. Given the new paradigm and the unique enabling technology of its high‐performance mechatronic system, the engineering and operational aspects for the next‐level beamline experimental possibilities with a double‐crystal monochromator are comprehensively discussed. Fly‐scan spectroscopy scientific commissioning results are also presented.
Background
Histopathological growth patterns (HGPs) are a prognostic biomarker in colorectal liver metastases (CRLM). Desmoplastic HGP (dHGP) is associated with liver-only recurrence and superior ...overall survival (OS), while non-dHGP is associated with multi-organ recurrence and inferior OS. This study investigated the predictive value of HGPs for adjuvant hepatic arterial infusion pump (HAIP) chemotherapy in CRLM.
Methods
Patients undergoing resection of CRLM and perioperative systemic chemotherapy in two centers were included. Survival outcomes and the predictive value of HAIP versus no HAIP per HGP group were evaluated through Kaplan–Meier and Cox regression methods, respectively.
Results
We included 1233 patients. In the dHGP group (
n
= 291, 24%), HAIP chemotherapy was administered in 75 patients (26%). In the non-dHGP group (
n
= 942, 76%), HAIP chemotherapy was administered in 247 patients (26%). dHGP was associated with improved overall survival (OS, HR 0.49, 95% CI 0.32–0.73,
p
< 0.001). HAIP chemotherapy was associated with improved OS (HR 0.61, 95% CI 0.45–0.82,
p
< 0.001). No interaction could be demonstrated between HGP and HAIP on OS (HR 1.29, 95% CI 0.72–2.32,
p
= 0.40).
Conclusions
There is no evidence that HGPs of CRLM modify the survival benefit of adjuvant HAIP chemotherapy in patients with resected CRLM.
MicroRNAs (miRNAs) are key regulators of gene expression. In this study, we explored whether altered miRNA expression has a prominent role in defining the inflammatory breast cancer (IBC) phenotype.
...We used quantitative PCR technology to evaluate the expression of 384 miRNAs in 20 IBC and 50 non-IBC samples. To gain understanding on the biological functions deregulated by aberrant miRNA expression, we looked for direct miRNA targets by performing pair-wise correlation coefficient analysis on expression levels of 10 962 messenger RNAs (mRNAs) and by comparing these results with predicted miRNA targets from TargetScan5.1.
We identified 13 miRNAs for which expression levels were able to correctly predict the nature of the sample analysed (IBC vs non-IBC). For these miRNAs, we detected a total of 17,295 correlated miRNA-mRNA pairs, of which 7012 and 10 283 pairs showed negative and positive correlations, respectively. For four miRNAs (miR-29a, miR-30b, miR-342-3p and miR-520a-5p), correlated genes were concordant with predicted targets. A gene set enrichment analysis on these genes demonstrated significant enrichment in biological processes related to cell proliferation and signal transduction.
This study represents, to the best of our knowledge, the first integrated analysis of miRNA and mRNA expression in IBC. We identified a set of 13 miRNAs of which expression differed between IBC and non-IBC, making these miRNAs candidate markers for the IBC subtype.
The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between ...lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment.
Summary
In malignant melanoma (MM) there is an urgent need to identify new markers with predictive value superior to the traditional clinical and histological parameters. Angiogenesis and ...lymphangiogenesis have been recognized as critical processes in tumour growth and metastasis development, and numerous studies have evaluated the significance of these parameters in predicting the prognosis in solid tumours, including MM. We set out to determine whether angiogenesis, lymphangiogenesis and lymphatic invasion (LI) are valuable prognostic markers in MM. We systematically reviewed the available literature and subsequently performed a meta‐analysis on the compiled data. To be eligible for the systematic review, a study had to provide the microvessel density (MVD), the lymphatic vessel density (LVD) or information about LI, assessed by immunohistochemistry on the primary site in patients with MM. To be evaluable for the meta‐analysis, a study also had to provide information on clinical outcome. We approached selected studies with the Reporting recommendations for tumour marker (REMARK) criteria, verifying whether they had followed the recommendations. In total, nine angiogenesis, seven lymphangiogenesis and 10 LI studies were included in our meta‐analysis, representing 419, 474 and 802 patients, respectively. Using meta‐analysis, we showed that peritumoral LVD and the presence of LI have prognostic value for patients with MM. In contrast, MVD and intratumoral LVD did not have prognostic value in these patients. LVD and LI seem to have prognostic value for patients with MM.
What's already known about this topic?
Both angiogenesis and lymphangiogenesis have been recognized as crucial processes in tumour growth and metastasis development.
In the last two decades, large numbers of studies evaluating microvessel and lymphatic vessel density in melanoma have been published, many of them reporting contradictory results.
What does this study add?
We performed a systematic review of all published data, followed by meta‐analysis, permitting a global evaluation of the existing evidence on the prognostic value of these parameters in melanoma.
The detection, enumeration and isolation of circulating tumour cells (CTCs) have considerable potential to influence the clinical management of patients with breast cancer. There is, however, ...substantial variability in the rates of positive samples using existing detection techniques. The lack of standardisation of technology hampers the implementation of CTC measurement in clinical routine practice.
This study was designed to directly compare three techniques for detecting CTCs in blood samples taken from 76 patients with metastatic breast cancer (MBC) and from 20 healthy controls: the CellSearch CTC System, the AdnaTest Breast Cancer Select/Detect and a previously developed real-time qRT-PCR assay for the detection of CK-19 and mammaglobin transcripts.
As a result, 36% of patients with MBC were positive by the CellSearch System, 22% by the AdnaTest, 26% using RT-PCR for CK-19 and 54% using RT-PCR for mammaglobin. Samples were significantly more likely to be positive for at least one mRNA marker using RT-PCR than using the CellSearch System (P=0.001) or the AdnaTest (P<0.001).
We observed a substantial variation in the detection rates of CTCs in blood from breast cancer patients using three different techniques. A higher rate of positive samples was observed using a combined qRT-PCR approach for CK-19 and mammaglobin, which suggests that this is currently the most sensitive technique for detecting CTCs.
Despite improved therapy of advanced colorectal cancer, the median overall survival (OS) is still low. A surgical removal has significantly improved survival, if lesions are entirely removed. The ...purpose of this retrospective explorative study was to evaluate the prognostic value of histological growth patterns (GP) in chemonaive and patients receiving neo-adjuvant therapy. Two-hundred-fifty-four patients who underwent liver resection of colorectal liver metastases between 2007 and 2011 were included in the study. Clinicopathological data and information on neo-adjuvant treatment were retrieved from patient and pathology records. Histological GP were evaluated and related to recurrence free and OS. Kaplan–Meier curves, log-rank test and Cox regression analysis were used. The 5-year OS was 41.8 % (95 % CI 33.8–49.8 %). Growth pattern evaluation of the largest liver metastasis was possible in 224 cases, with the following distribution: desmoplastic 63 patients (28.1 %); pushing 77 patients (34.4 %); replacement 28 patients (12.5 %); mixed 56 patients (25.0 %). The Kaplan–Meier analyses demonstrated that patients resected for liver metastases with desmoplastic growth pattern had a longer recurrence free survival (RFS) than patients resected for non-desmoplastic liver metastases (p = 0.05). When patients were stratified according to neo-adjuvant treatment in the multivariate Cox regression model, hazard ratios for RFS compared to desmoplastic were: pushing (HR = 1.37, 95 % CI 0.93–2.02, p = 0.116), replacement (HR = 2.16, 95 % CI 1.29–3.62, p = 0.003) and mixed (HR = 1.70, 95 % CI 1.12–2.59, p = 0.013). This was true for chemonaive patients as well as for patients who received neo-adjuvant treatment.
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