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Matrix metalloproteinase-2 (MMP-2) is a gelatinase and is involved in multiple steps of the metastatic cascade. More than a decade ago an increased expression of MMP-2 in tumour cells or higher serum levels was reported to be a prognostic biomarker for a lower disease-free and overall survival rate. In recent years new evidence has indicated that MMP-2 has an important role in the tumour ecosystem. It is one of the many players in the onco-sphere, involved in interacting between tumour cells, host cells and the microenvironment. It plays a role in the dissemination of tumour cells, the epithelial–mesenchymal and mesenchymal–epithelial transitions, the formation of the pre-metastatic and metastatic niches, dormancy of tumour cells and modulating the immune system. The aim of this review is to highlight these multiple roles in the metastatic cascade and how many signalling pathways can up or down-regulate MMP-2 activity in the different stages of cancer progression and the effect of MMP-2 on the onco-sphere. Research in head and neck cancer is used as an example of these processes. The use of non-specific MMP inhibitors has been unsuccessful showing only limited benefits and associated with high toxicity as such that none have progressed past Phase III trials. Preclinical trials are undergoing using antibodies directed against specific matrix metalloproteinases, these targeted therapies may be potentially less toxic to the patients. [ABSTRACT FROM AUTHOR]

Aim: Despite curative surgery, 25% of patients with Stage II colorectal cancer will relapse due to minimal residual disease (MRD). Markers of immune function, such as the neutrophil to lymphocyte ratio (NLR), may be associated with MRD defined by bone marrow micro‐metastasis (mM) and circulating tumour cells (CTCs). Method: A prospective cohort study of consecutive patients with Stage II colon cancer patients attended at a single centre between 2007 and 2014. Blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti‐carcinoembryonic antigen 1 month after surgery. The NLR and absolute neutrophil and lymphocyte counts were determined immediately pre‐surgery and 1 month post‐surgery. These were compared with the sub‐types of MRD: group I MRD(−); group II mM positive and group III CTC positive. Cut‐off values of the NLR of >3.0 and >5.0 were used. Follow‐up was for up to 5 years or relapse and disease‐free survival (DFS) was calculated using Kaplan–Meier analysis. Results: In all, 181 patients (99 women) participated. Mean age was 68 years. Median follow‐up was 4.04 years: I, N = 105; II, N = 36; III, N = 40. The NLR significantly decreased post‐surgery only in group I patients. The frequency of NLR >3.0 and >5.0 was significantly higher in group III; between groups I and II there was no significant difference. 5‐year DFS was 98% in group I, 68% in group II and 7% in group III. Conclusions: Patients with a significantly higher immune dysfunction had a shorter time to disease progression, a worse DFS and the presence of CTCs. [ABSTRACT FROM AUTHOR]

Objective: The Epstein criteria (EC) used to select men for active surveillance do not predict biologically insignificant diseases. Minimal residual disease (MRD) is an undetected microscopic disease that remains after radical prostectomy (RP) and is a biological classification associated with the risk of treatment failure. Subtypes of MRD, the 10-year biochemical failure free survival (BFFS), and restricted mean biochemical failure free survival time (RMST) were determined and compared in EC patients treated with RP.Material and methods: Consecutive patients with a Gleason 6 biopsy treated at a single institution were divided into those who did or did not fulfill the EC and underwent RP. One month after surgery, samples were taken for the detection of circulating prostate cells (CPCs) and bone marrow micrometastasis. MRD was defined as negative for both CPCs and micrometastasis; patients were positive for micrometastasis and CPCs separately. BFFS for up to 10 years and RMST were determined for each MRD subgroup for EC positive and negative patients.Results: EC positive men (137/426) were significantly older (p<0.05) and had negative MRD, pT2 (pathologically organ confined) disease (<0.02), and lower frequency of upgrading (p<0.02). Of the EC positive men, 71% were MRD negative, 13% were positive for micrometastasis, and 16% were positive for CPCs with respective 10-year BFFS of 99%, 89%, and 21% (<0.001) (hazard ratio: 1.00, 1.76, 4.03, respectively) with no signficant differences between the 10-year BFFS or RMST for MRD subgroups for EC positive and negative patients.Conclusions: EC predict pT2, MRD negative disease; however, 29% are MRD positive with a high risk of treatment failure. [ABSTRACT FROM AUTHOR]

Purpose: To compare Gleason score (GS), pathological stage, minimal residual disease (MRD) and outcome after prostatectomy radical for prostate cancer.Patients and Methods: 290/357 men with GS 6 or 7 and pT2 or pT3a disease treated with radical prostatectomy participated. Blood and bone marrow were obtained one month after surgery. Circulating prostate cells (CPCs) were detected using differential gel centrifugation and immunocytochemistry with anti PSA, micro-metastasis weas detected using immunocytochemistry with anti-PSA. Biochemical failure free survival (BFFS) and restricted mean survival times (RMST) were calculated according to GS and stage. MRD was classified as negative, patients only positive for micro-metastasis and patients positive for CPCs; BFFS and RMST were calculated according to MRD sub-type.Results: GS7 (HR 3.03) and pT3a (HR 3.68) cancers were associated with a higher failure rate, shorter time to failure and associated with CPC positive MRD (p < 0.001), while G6 and pT2 with MRD negative disease (p<0.001). Men with CPC (+) MRD were at high risk of early treatment failure; 15% BFFS at 10 years, RMST 3.0 years. Men positive for only micro-metastasis were at risk of late failure, 50% BFFS at 10 years, RMST 8.0 years compared with MRD negative patients; 80% BFFS at 10 years, RMST 9.0 years.Conclusion: The sub-type of MRD identifies Gleason 6 pT2 patients with a poor prognosis and Gleason 7 pT3a patients with a good prognosis and could be used to classify men according to personal risk characteristics for the use of adjuvant treatment. [ABSTRACT FROM AUTHOR]