Comment on 'Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area'

We comment on the recent study by Sideras et al (2015) that combines tissue microarrays (TMAs) and immunohistochemistry to investigate the expression pattern of 15 antigens belonging to different categories, including cancer-testis antigens and oncofetal proteins in hepatocellular carcinoma (HCC). Because current therapies for HCC are far from ideal (Ilan, 2014) and immunotherapy has been suggested as a potential therapeutic option, the Authors aimed at identifying a panel of biologically relevant tumour antigens with broad expression in a western European population of HCC patients and specific expression in the tumour tissue with no, or little, expression in surrounding non- tumoral tissue (Sideras et al., 2015)

Epithelial to mesenchymal transition: A challenging playground for translational research. current models and focus on TWIST1 relevance and gastrointestinal cancers

Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal‐like ones. Along the transition, a full‐blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed E⇔M states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI)

Immune cells : plastic players along colorectal cancer progression

Inflammatory cells are involved in tumour initiation and progression. In parallel, the adaptive immune response plays a key role in fighting tumour growth and dissemination. The double-edged role of the immune system in solid tumours is well represented in colorectal cancer (CRC). The development and progression of CRC are affected by the interactions between the tumour and the host's response, occurring in a milieu named tumour microenvironment. The role of immune cells in human CRC is being unravelled and there is a strong interest in understanding their dynamics as to tumour promotion, immunosurveillance and immunoevasion. A better definition of immune infiltration would be important not only with respect to the 'natural history' of CRC, but in a clinically relevant perspective in the 21st century, with respect to its post-surgical management, including chemotherapy responsiveness. While it is becoming established that the amount of tumour-infiltrating lymphocytes influences the post-surgical progression of early-stage CRC, the relevance of this immune parameter as to chemotherapy responsiveness remains to be clarified. Despite recent experimental work supporting the notion that infiltrating immune cells may influence chemotherapy-mediated tumour cell death, tumour-infiltrating cells are not employed to identify patients who are more likely to benefit from adjuvant treatment. This review focuses on studies addressing the role of innate and adaptive immune cells along the occurrence and the progression of potentially curable CRC

Impact of time to surgery after neoadjuvant chemotherapy in patients with operable breast cancer.

Background: Some studies of adjuvant chemotherapy (CT) suggested that a shorter interval before the start of therapies may improve survival outcomes in many groups of patients. Time to surgery (TTS) after neoadjuvant CT and survival outcomes have not been established yet. The aim of this study is to evaluate the impact of TTS after neoadjuvant CT in terms of Overall Survival (OS) and Disease Free Survival (DFS). Patients and Methods: A retrospective analysis was conducted in 295 patients receiving neoadjuvant CT for stage I-IIIc breast cancer between 1991 and 2013. 56 pts underwent surgery within 21 days (group A) from last CT cycle, 148 pts within 22-35 days (group B) and 91 pts after 36 days (group C). The majority were infiltrating ductal carcinoma, stage IIA (37.6%) and IIB (33.9%), with nodal involvement in 51.6% of the cases. LumA 18.3%, LumB/HER2- 28.2%, LumB/Her2+ 20.7%, HER2+ 9.8%, TNBC 21%. All patients were treated with neoadjuvant CT: 70.5% with anthra-taxanes based regimen, 18% with anthra- alone, 10.9% with taxanes alone, 0.3% with CMF; plus Trastuzumab in 70% of HER2+ diseases. Results: After a median follow up of 4.6 years, it was observed that patients in group A showed a significant better OS than group B (HR 4.22; 95% CI, 1.27 \u2013 14.00, p=0.018) and group C (HR 3.61; 95% CI, 1.01 \u2013 12.86, p=0.048). Moreover group A showed a significant better DFS than group B (HR 3.41; 95% CI 1.34 to 8.65, p=0.010) and group C (HR 3.77; 95% CI 1.42 to 9.95, p=0.007). No correlations with OS were found in pts who achieved pCR (20.7%); pCR was predictive of better 5- and 10-years DFS independently from TTS (95.4% in the pCR-group vs 75.4% of non-pCR group, HR 0.16; 95% CI 0.04 to 0.66, p=0.011). TTS may influence DFS in non-pCR group: indeed 5-years DFS is 97.3% in group A, 72.7% in group B (HR 2.89; 95% CI 1.14 to 7.36, p=0.026), and 68.5% in group C (HR 3.44; 95% CI 1.3 to 9.1, p=0.013). No significant correlations with regard of stage at diagnosis or molecular subtypes were found. Conclusions: These results suggest that TTS after primary CT may influence patients' survival, regardless of stage at diagnosis and tumor subtype, so that a shorter interval between that last cycle of neoadjuvant chemotherapy and breast surgery should be addressed whenever possible

Sperm protein 17 is expressed in human nervous system tumours

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells

Prognostic value of innate and adaptive immunity in colorectal cancer

Colorectal cancer (CRC) remains one of the major public health problems throughout the world. Originally depicted as a multi-step dynamical disease, CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states, from single crypt lesions through adenoma, to malignant carcinoma with the potential for invasion and metastasis. Moving from histological observations since a long time, it has been recognized that inflammation and immunity actively participate in the pathogenesis, surveillance and progression of CRC. The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC. It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment. Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival. Several lines of evidence support the concept that tumor stromal cells, are not merely a scaffold, but rather they influence growth, survival, and invasiveness of cancer cells, dynamically contributing to the tumor microenvironment, together with immune cells. Different types of immune cells infiltrate CRC, comprising cells of both the innate and adaptive immune system. A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation, invasion, and dissemination induced by some types of inflammatory cells. Here, we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC, and the prognostic information that we can currently understand and exploit

Cancer initiation and progression: an unsimplifiable complexity

BACKGROUND: Cancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated. CONCLUSION: There is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours

Early Detection of Prostate Cancer: The Role of Scent

Prostate cancer (PCa) represents the cause of the second highest number of cancer-related deaths worldwide, and its clinical presentation can range from slow-growing to rapidly spreading metastatic disease. As the characteristics of most cases of PCa remains incompletely understood, it is crucial to identify new biomarkers that can aid in early detection. Despite the prostate-specific antigen serum (PSA) levels, prostate biopsy, and imaging representing the actual gold-standard for diagnosing PCa, analyzing volatile organic compounds (VOCs) has emerged as a promising new frontier. We and other authors have reported that highly trained dogs can recognize specific VOCs associated with PCa with high accuracy. However, using dogs in clinical practice has several limitations. To exploit the potential of VOCs, an electronic nose (eNose) that mimics the dog olfactory system and can potentially be used in clinical practice was designed. To explore the eNose as an alternative to dogs in diagnosing PCa, we conducted a systematic literature review and meta-analysis of available studies. PRISMA guidelines were used for the identification, screening, eligibility, and selection process. We included six studies that employed trained dogs and found that the pooled diagnostic sensitivity was 0.87 (95% CI 0.86–0.89; I2, 98.6%), the diagnostic specificity was 0.83 (95% CI 0.80–0.85; I2, 98.1%), and the area under the summary receiver operating characteristic curve (sROC) was 0.64 (standard error, 0.25). We also analyzed five studies that used an eNose to diagnose PCa and found that the pooled diagnostic sensitivity was 0.84 (95% CI, 0.80–0.88; I2, 57.1%), the diagnostic specificity was 0.88 (95% CI, 0.84–0.91; I2, 66%), and the area under the sROC was 0.93 (standard error, 0.03). These pooled results suggest that while highly trained dogs have the potentiality to diagnose PCa, the ability is primarily related to olfactory physiology and training methodology. The adoption of advanced analytical techniques, such as eNose, poses a significant challenge in the field of clinical practice due to their growing effectiveness. Nevertheless, the presence of limitations and the requirement for meticulous study design continue to present challenges when employing eNoses for the diagnosis of PCa