The Expression of Forkhead Box P3 T Regulatory Lymphocytes as a Prognostic Factor in Malignant Melanomas.

Since transcription factor Forkhead Box P3 (FoxP3) was identified as a specific regulatory T cell (Treg) marker, researchers have scrutinized its value as a potential novel therapeutic target or a prognostic factor in various types of cancer with inconsistent results. The present analysis was performed to assess the influence of Treg FoxP3 expression on the prognosis of primary melanoma and to evaluate the correlations with various clinicopathological prognostic factors. We analyzed all eligible patients with stage pT3 primary malignant melanomas treated in a tertiary cancer center. Immunohistochemical staining for Treg FoxP3 expression was performed on retrospectively identified paraffin blocks and subsequently correlated with the outcomes of the patients. A total of 81% of the patients presented a positive Treg FoxP3 expression, being correlated with a higher risk of lymph node metastasis, tumor relapse, and death. Moreover, positive expression was statistically associated with a shorter OS. The tumor relapse rate was estimated at 36.7%. A positive expression of Treg FoxP3 and lymph node metastasis were associated with a higher risk of death based on multivariate analysis. Treg FoxP3 expression may be used as an independent prognostic factor in patients with malignant melanoma to evaluate tumor progression and survival.

Molecular Subtypes, microRNAs and Immunotherapy Response in Metastatic Colorectal Cancer.

Currently, only a limited set of molecular traits are utilized to direct treatment for metastatic CRC (mCRC). The molecular classification of CRC depicts tumor heterogeneity based on gene expression patterns and aids in comprehending the biological characteristics of tumor formation, growth and prognosis. Additionally, it assists physicians in tailoring the therapeutic approach. Microsatellite instability (MSI-H)/deficient mismatch repair proteins (MMRd) status has become a ubiquitous biomarker in solid tumors, caused by mutations or methylation of genes and, in turn, the accumulation of mutations and antigens that subsequently induce an immune response. Immune checkpoint inhibitors (ICI) have recently received approval for the treatment of mCRC with MSI-H/MMRd status. However, certain individuals experience either initial or acquired resistance. The tumor-programmed cell death ligand 1 (PD-L1) has been linked to the ability of CRC to evade the immune system and promote its growth. Through comprehensive research conducted via the PUBMED database, the objectives of this paper were to review the molecular characteristics linked to tumor response in metastatic CRC in light of improved patients' outcomes following ICI therapies as seen in clinical trials and to identify particular microRNAs that can modulate the expression of specific oncoproteins, such as PD-L1, and disrupt the mechanisms that allow the immune system to be evaded.

Exosomes in Colorectal Cancer: From Physiology to Clinical Applications.

Exosomes are nanosized vesicles that have been found to be involved in many diseases. Exosomes can mediate communication between cells in a variety of ways. Certain types of mediators derived from cancer cells can play a crucial role in the development of this pathology, promoting tumor growth, invasion, metastasis, angiogenesis, and immunomodulation. Exosomes in the bloodstream show promise as a future tool for detecting cancer at an early stage. The sensitivity and specificity of clinical exosome biomarkers need to be enhanced. Knowledge of exosomes is not only important for understanding the significance of cancer progression but also for providing clinicians with useful information for the diagnosis, treatment, and discovery of methods to prevent cancer from recurring. The widespread adoption of diagnostic tools based on exosomes may revolutionize cancer diagnosis and treatment. Tumor metastasis, chemoresistance, and immunity are all aided by exosomes. A potential new approach to cancer therapy involves preventing metastasis by inhibiting miRNA intracellular signaling and blocking the formation of pre-metastatic niches. For colorectal patients, exosomes represent a promising area of investigation for improving the diagnosis, treatment, and management. Reported data demonstrate that the serum expression level of certain exosomal miRNA is significantly higher in primary colorectal cancer patients. The present review discusses mechanisms and clinical implications of exosomes in colorectal cancer.

Tumor Lysis Syndrome: An Endless Challenge in Onco-Nephrology.

Tumor lysis syndrome (TLS) is a common cause of acute kidney injury in patients with malignancies, and it is a frequent condition for which the nephrologist is consulted in the case of the hospitalized oncological patient. Recognizing the patients at risk of developing TLS is essential, and so is the prophylactic treatment. The initiation of treatment for TLS is a medical emergency that must be addressed in a multidisciplinary team (oncologist, nephrologist, critical care physician) in order to reduce the risk of death and that of chronic renal impairment. TLS can occur spontaneously in the case of high tumor burden or may be caused by the initiation of highly efficient anti-tumor therapies, such as chemotherapy, radiation therapy, dexamethasone, monoclonal antibodies, CAR-T therapy, or hematopoietic stem cell transplantation. It is caused by lysis of tumor cells and the release of cellular components in the circulation, resulting in electrolytes and metabolic disturbances that can lead to organ dysfunction and even death. The aim of this paper is to review the scientific data on the updated definition of TLS, epidemiology, pathogenesis, and recognition of patients at risk of developing TLS, as well as to point out the recent advances in TLS treatment.

Paraparesis and Disseminated Osteolytic Lesions Revealing Cholangiocarcinoma: A Case Report.

Bone metastases in cholangiocarcinoma are uncommon. We report the case of a patient with disseminated osteolytic lesions who was admitted to the Neurology Department for progressive paraparesis. On the computed tomography examination, specific features for cholangiocarcinoma were described, confirmed later by the histopathological aspect of the bone lesions.

The value of tumor infiltrating lymphocytes as prognostic factor for lymph node status and survival amongst patients with cutaneous malignant melanoma.

PURPOSE: Tumor infiltrating lymphocytes (TILs) in cutaneous malignant melanoma are classified as brisk, non-brisk or absent. Numerous studies suggest the presence of TILs, especially brisk, are associated with a lower rate of lymph node metastasis and with an improved overall survival (OS). Our purpose was to assess the value of TILs as a prognostic factor for the lymph node metastasis and survival in completely resected pT3 stage malignant melanoma patients. METHODS: We included a number of 114 patients with pathological pT3 cutaneous malignant melanoma, treated exclusively in our institution, between 2000-2015. Correlations of clinical and pathological factors with lymph node status and OS were analyzed. RESULTS: A brisk infiltrate was present in 60% of the patients, whereas 40% presented a non-brisk infiltrate or absent TILs. In univariate analysis, the presence of ulceration was correlated with a non-brisk infiltrate, whereas in multivariate analysis, lymph node invasion and a non-brisk infiltrate were associated with a higher risk of death. CONCLUSIONS: TILs density grade represents an independent prognostic factor for the OS. Therefore, we conclude that an accurate prognosis may be provided by TILs status in patients with pT3 malignant melanoma.

The role of CD146 in serous ovarian carcinoma.

PURPOSE: The heterogeneous phenotype of epithelial ovarian cancer (EOC) explains the unpredictable behaviour in terms of response to therapy, time to progression and survival. In this context, CD146, a cell adhesion molecule, has been focused on as a marker of poor prognosis in various solid cancers, being also capable to modulate the activity of endothelial cells. Therefore, we proposed to investigate its role in serous ovarian carcinoma. METHODS: The study included 101 patients diagnosed with EOC and treated within "Ion Chiricuta" Oncology Institute by optimal surgical debulking followed by platinum-based chemotherapy. Clinico-pathological characteristics were collected from patient files. CD146 expression was assessed by immunohistochemistry in serous ovarian carcinoma primary tumours, taking into account both staining intensity and the percentage of positive tumor cells. Expression of CD146 in endothelial cells of tumour microvessels was also evaluated. CD34 immunostaining was used for intratumoral microvessel density estimation. RESULTS: CD146 positivity in tumor cells was objectified in 49.5% of samples and 37.1% presented a high CD146 endothelial expression. Our analysis showed that CD146 was as reliable as CD34 for microvascular density estimation. The distribution of cases according to CD146 tumor expression was similar regardless of age, initial serum CA125 level, FIGO stage, presence/absence of malignant ascites. Multivariate analysis confirmed that expression of CD146 in tumor cells was a negative prognostic factor for overall survival, significantly asociated with a higher risk of chemotherapy resistance. CONCLUSIONS: Although CD146 immunoreactivity in tumor cells did not correlate with the routinely used clinico-pathological parameters, expression of CD146 in tumor cells was an independent pronostic factor for survival in serous ovarian carcinomas. Moreover, CD146 might be regarded as a novel biomarker of tumor neovasculature.

Expression of toll-like receptors in ovarian cancer.

PURPOSE: Ovarian cancer continues to be the most lethal gynecologic malignancy, with a complex tumor microenvironment (TME). We investigated the immunohistochemical (IHC) expression of toll like receptors (TLRs) 4,5,7 and 9 together with CD68 and CD 163 as markers for tumor-associated macrophages (TAM) in relation to clinicopathological data. METHODS: Data from 102 patients with serous ovarian cancer treated between 2006 and 2011 was retrospectively reviewed. A TLR IHC score was developed and CD68, CD163 density scores were calculated as the mean number of positive cells from three 0.5 mm2 areas. RESULTS: Advanced-stage disease (FIGO IIIC-IV) was present in 65.7% of cases. A TLR4 score above median was associated with peritoneal carcinomatosis (odds ratio/OR) 3.02, p=0.019) or ascites (OR 2.5, p=0.041). In FIGO stage IIIC-IV patients with a platinum-free interval (PFI) >12 months had, in comparison with patients with PFI ≤12 months, a higher CD68 density score (191.9 ± 95.2 vs. 152.7 ± 69.4, p=0.066) and a lower CD163 density score (106.7 ± 73.3 vs. 154.5 ± 73.9, p=0.011). In early-stage ovarian cancer patients, TLR9 positivity was associated with a higher overall survival than in patients with absent expression (110.2 vs. 22 months, p<0.001), while advanced-stage patients with TLR7 positivity had a lower overall survival than patients with negative TLR7 (38.3 vs. 66.2 months, p=0.01). CONCLUSIONS: Our data shows that TLRs and TAM are important prognostic markers and future studies are needed to better comprehend the immune response in ovarian cancer.