Molecular Detection of Lymph Node Metastases with One-Step Nucleic Acid Amplification (OSNA) Pooling in Prostate Cancer: The POPCORN Study.

Pelvic lymph node dissection (PLND) is the most accurate procedure for lymph node (LN) staging in prostate cancer (PCa) patients. LN sectioning and hematoxylin and eosin (H&E) staining of at least one slice remains the gold standard for LN evaluation, potentially leading to misdetection of small metastatic focus. Entire LN analysis is possible with One-Step Nucleic Acid Amplification (OSNA) by detecting cytokeratin 19 (CK19) mRNA as a surrogate for LN invasion.

Personalized Medicine in Acromegaly: The ACROFAST Study.

Context: Medical treatment of acromegaly is currently performed through a trial-and-error approach using first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response.

Objective: Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated.

The C250T Mutation of Might Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation.

Unlabelled: The aim of this study was to determine how mutations impact glioblastoma prognosis.

Materials And Methods: mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients.

New molecular tools for precision medicine in pituitary neuroendocrine tumors.

Precision, personalized, or individualized medicine in pituitary neuroendocrine tumors (PitNETs) has become a major topic in the last few years. It is based on the use of biomarkers that predictively segregate patients and give answers to clinically relevant questions that help us in the individualization of their management. It allows us to make early diagnosis, predict response to medical treatments, predict surgical outcomes and investigate new targets for therapeutic molecules.

Predictive signature of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer integrating mRNA expression, taxonomic subtypes, and clinicopathological features.

Background And Objective: Neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care in muscle-invasive bladder cancer (MIBC). Pathological response has been associated with longer survival, but no currently available clinicopathological variables can identify patients likely to respond, highlighting the need for predictive biomarkers. We sought to identify a predictive signature of response to NAC integrating clinical score, taxonomic subtype, and gene expression.

Molecular characterization of epithelial-mesenchymal transition and medical treatment related-genes in non-functioning pituitary neuroendocrine tumors.

Introduction: Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas.

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population.

In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma.

RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas.

Preoperative Diagnosis and Molecular Characterization of Gliomas With Liquid Biopsy and Radiogenomics.

Gliomas are a heterogenous group of central nervous system tumors with different outcomes and different therapeutic needs. Glioblastoma, the most common subtype in adults, has a very poor prognosis and disabling consequences. The World Health Organization (WHO) classification specifies that the typing and grading of gliomas should include molecular markers.

Data mining analyses for precision medicine in acromegaly: a proof of concept.

Predicting which acromegaly patients could benefit from somatostatin receptor ligands (SRL) is a must for personalized medicine. Although many biomarkers linked to SRL response have been identified, there is no consensus criterion on how to assign this pharmacologic treatment according to biomarker levels. Our aim is to provide better predictive tools for an accurate acromegaly patient stratification regarding the ability to respond to SRL.

Implications of Heterogeneity of Epithelial-Mesenchymal States in Acromegaly Therapeutic Pharmacologic Response.

Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs.

Prognostic Impact of CD36 Immunohistochemical Expression in Patients with Muscle-Invasive Bladder Cancer Treated with Cystectomy and Adjuvant Chemotherapy.

Neoadjuvant chemotherapy followed by a cystectomy is the standard treatment in muscle-invasive bladder cancer (MIBC). However, the role of chemotherapy in the adjuvant setting remains controversial, and therefore new prognostic and predictive biomarkers are needed to improve the selection of MIBC patients. While lipid metabolism has been related to several biological processes in many tumours, including bladder cancer, no metabolic biomarkers have been identified as prognostic in routine clinical practice.

Glioblastoma: Relationship between Metabolism and Immunosuppressive Microenvironment.

Glioblastoma (GBM) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping this tumor microenvironment (TME) regulate tumor initiation, progression, and treatment response. Genetic alterations and metabolism pathways are two main elements that influence tumor immune cells and TME.

MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin.

Epithelial to mesenchymal transition (EMT) is an important mechanism of invasion in cutaneous squamous cell carcinomas (cSCCs) and has been found to be enhanced in tumors originated from actinic keratosis with transformation limited to the basal epithelial layer -differentiated pathway-, compared to cases with invasion subsequent to complete epidermal transformation -classical pathway-. Several microRNAs and proteins can contribute to EMT modulation in cSCCs. MicroRNA21 and microRNA31 are involved in posttranscriptional regulation of protein expression and could play a relevant role in EMT and cSCC progression.

The Challenge of Diagnosing Constitutional Mismatch Repair Deficiency Syndrome in Brain Malignancies from Young Individuals.

Biallelic germline mismatch repair (MMR) gene and mutations are an extremely rare event that causes constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD is underdiagnosed and often debuts with pediatric malignant brain tumors. A high degree of clinical awareness of the CMMRD phenotype is needed to identify new cases.

Characteristics of Adrenocortical Carcinoma Associated With Lynch Syndrome.

Context: Lynch syndrome (LS) is the most common inherited colorectal and endometrial cancer syndrome, caused by germline mutations in DNA mismatch repair (MMR) genes. It is also characterized by an increased risk of other tumors with lower prevalence, such as adrenal cortical carcinoma (ACC), an endocrine tumor with an incidence of <2 cases/million individuals/year. Most ACC developed during childhood are associated with hereditary syndromes.

Complete Loss of EPCAM Immunoexpression Identifies Deletion Carriers in MSH2-Negative Colorectal Neoplasia.

The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), precursor lesions of gastrointestinal (71) and extra-gastrointestinal origin (9), and benign neoplasms (8) from different organs of 71 patients suspicious of being LS due to alterations.

Glioblastoma TCGA Mesenchymal and IGS 23 Tumors are Identifiable by IHC and have an Immune-phenotype Indicating a Potential Benefit from Immunotherapy.

Purpose: Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice.

Experimental Design: Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities.

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH-producing adenomas.

Objective: Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter.

Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going?

Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the recommended treatment, with the highest level of evidence, for patients with muscle-invasive bladder cancer (MIBC). However, only a minority of patients receive this treatment, mainly due to patient comorbidities, the relatively small survival benefit, and the lack of predictive biomarkers to select those patients most likely to benefit from this multimodal approach. In addition, adjuvant chemotherapy has been recommended for patients with high-risk MIBC, although randomized trials have not provided conclusive evidence on the impact of this approach.

Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns.

Background: There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB.

Method: Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016.