Corrigendum: The molecular tumor board as a step in cancer patient management: a southern Italian experience.

[This corrects the article DOI: 10.3389/fmed.2024.

The molecular tumor board as a step in cancer patient management: a southern Italian experience.

Introduction: The management of cancer patients follows a Diagnostic Therapeutic and Care Pathway (PDTA) approach, aimed at achieving the optimal balance between care and quality of life. To support this process, precision medicine and innovative technologies [e.g.

Successful treatment of a non-small-cell lung cancer patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del with alectinib.

This is the first case report of a non-small-cell lung cancer (NSCLC) patient harboring HIP1-ALK (H28:A20) and CTNNB1 p.S45del treated with first-line alectinib. Approximately 5% of NSCLC patients are reported to have anaplastic lymphoma kinase (ALK) rearrangements, and among these EML4-ALK is the most frequent fusion variant.

Concomitant Immunotherapy and Metastasis-Directed Radiotherapy in Upper Tract Urothelial Carcinoma: A Biomarker-Driven, Original, Case-Based Proof-of-Concept Study.

Metastatic upper tract urothelial carcinoma (mUTUC) has a poor prognosis. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in patients with metastatic urothelial carcinoma. However, data supporting the use of ICIs in patients with mUTUC are limited.

An Italian Multicenter Perspective Harmonization Trial for the Assessment of MET Exon 14 Skipping Mutations in Standard Reference Samples.

Lung cancer remains the leading cause of cancer deaths worldwide. International societies have promoted the molecular analysis of MET proto-oncogene, receptor tyrosine kinase () exon 14 skipping for the clinical stratification of non-small cell lung cancer (NSCLC) patients. Different technical approaches are available to detect exon 14 skipping in routine practice.

Multiple Genetic Alterations as Resistance Mechanism during Second-Line Lorlatinib for Advanced ALK-Rearranged Lung Adenocarcinoma: A Case Report.

Second and third-generation ALK-TKI inhibitors have showed better activity and have replaced crizotinib in most of cases of advanced ALK-rearranged lung adenocarcinoma. The emergence of resistance adversely affects also the activity of these newer drugs; in particular, lorlatinib often shows multiple and complex resistance mechanisms. The case reported here highlights the importance of reassessing the biomolecular profile during the disease course, both by tissutal and liquid biopsy, with the aim of improving the knowledge of these resistance mechanisms, and so identifying new drugs or sequences able to optimize the management of these patients.

A Promising Role of TGF-β Pathway in Response to Regorafenib in Metastatic Colorectal Cancer: A Case Report.

Colorectal cancer (CRC) is one of the most common cancer types around the world. The prognosis of patients with advanced diseases is still poor in spite of currently available therapeutic options. Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved to treat refractory metastatic colorectal cancer (mCRC).

The ERRα-VDR axis promotes calcitriol degradation and estrogen signaling in breast cancer cells, while VDR-CYP24A1-ERRα overexpression correlates with poor prognosis in patients with basal-like breast cancer.

Vitamin D is used to reduce cancer risk and improve the outcome of cancer patients, but the vitamin D receptor (VDR; also known as the calcitriol receptor) pathway needs to be functionally intact to ensure the biological effects of circulating calcitriol, the active form of vitamin D. Besides estrogen receptor alpha (ERα), estrogen-related receptor alpha (ERRα) has also been shown to interfere with the VDR pathway, but its role in the antitumor and transactivation activity of calcitriol is completely unknown in breast cancer (BC). We observed that ERRα functionally supported the proliferation of BC cell lines and acted as a calcitriol-induced regulator of VDR.

Harmonization of Next-Generation Sequencing Procedure in Italian Laboratories: A Multi-Institutional Evaluation of the SiRe® Panel.

Next-generation sequencing (NGS) needs to be validated and standardized to ensure that cancer patients are reliably selected for target treatments. In Italy, NGS is performed in several institutions and harmonization of wet and dry procedures is needed. To this end, a consortium of five different laboratories, covering the most part of the Italian peninsula, was constituted.

KRAS-Driven Lung Adenocarcinoma and B Cell Infiltration: Novel Insights for Immunotherapy.

Non-small-cell lung cancer, histologically classified into adenocarcinoma (AD) and squamous cell carcinoma, is one of the most deadly malignancies worldwide. Lung AD (LUAD) could benefit of a plethora of target therapies and, in the last few years, also of immunotherapies. Here we focused on a real-life cohort of LUAD and The Cancer Genome Atlas (TCGA)-LUAD dataset aiming to gain insights into the immune contexture of such a malignancy.

Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non-Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases.

Background: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non-small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases.

Six low-penetrance SNPs for the estimation of breast cancer heritability: A family-based study in Caucasian Italian patients.

Breast cancer is a malignancy with a strong heritable component. Genetic counseling has been principally focused on families carrying high-penetrance genes. Current modeling suggests that the majority of the unexplained fraction of familial risk is likely to be explained by a polygenic model.

TGFbeta and miRNA regulation in familial and sporadic breast cancer.

The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups.

u-PAR expression in cancer associated fibroblast: new acquisitions in multiple myeloma progression.

Background: Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF.

Next-generation sequencing: advances and applications in cancer diagnosis.

Technological advances have led to the introduction of next-generation sequencing (NGS) platforms in cancer investigation. NGS allows massive parallel sequencing that affords maximal tumor genomic assessment. NGS approaches are different, and concern DNA and RNA analysis.

BRCA1-2 diagnostic workflow from next-generation sequencing technologies to variant identification and final report.

The BRCA1-BRCA2 genes predispose to hereditary breast and ovarian cancer, and the germline and mutational status of these genes defines a target population that can benefit from PARP inhibitor treatments. To respond to the increasing number of BRCA1-BRCA2 tests, it is necessary to shift to high-throughput technologies that are reliable and less time consuming. Different methodological platforms are dedicated to this purpose with different approaches and algorithms for analysis.

The European accreditation of Istituto Tumori Giovanni Paolo II of Bari.

The National Cancer Institute of Bari (Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS) has been involved since the conception of the project of the Italian Ministry for Health aimed to validate the applicability of the Organisation of European Cancer Institutes (OECI) accreditation and designation (A&D) model to the Network of Italian Cancer Centers, IRCCS, of Alleanza Contro il Cancro. The self-assessment phase of the Institute started in September 2013 and ended in June 2014. All documents and tools were transferred to the OECI A&D Board in June 2014 and a 2-day peer review visit was conducted in October 2014 by an international qualified audit team.

miRNA profiling in serum and tissue samples to assess noninvasive biomarkers for NSCLC clinical outcome.

In NSCLC, the altered expression of some miRNAs in primary tumor tissues has been correlated with diagnosis and prognosis, while the role of circulating miRNAs as cancer biomarkers is currently emerging. MiRNA expression profile through miRNA Affymetrix array was evaluated on a training set formed by the tumor component (n = 30 NSCLC serum, n = 11/30 tumor tissues) and the control component (n = 10 healthy serum and n = 11/30 noncancerous counterparts). Statistical analyses highlighted the following: a = 55 miRNAs deregulated in tumor serum, b = 27 miRNAs deregulated in tumor tissues, and c = 2 miRNAs deregulated both in tumor serum and in tumor tissues.

Accreditation for excellence of cancer research institutes: recommendations from the Italian Network of Comprehensive Cancer Centers.

A panel of experts from Italian Comprehensive Cancer Centers defines the recommendations for external quality control programs aimed to accreditation to excellence of these institutes. After definition of the process as a systematic, periodic evaluation performed by an external agency to verify whether a health organization possesses certain prerequisites regarding structural, organizational and operational conditions that are thought to affect health care quality, the panel reviews models internationally available and makes final recommendations on aspects considered of main interest. This position paper has been produced within a special project of the Ministry of Health of the Italian Government aimed to accredit, according to OECI model, 11 Italian cancer centers in the period 2012-2014.

Genetic risk transmission in a family affected by familial breast cancer.

Breast Cancer is the most common malignancy among women. Family history is the strongest single predictor of breast cancer risk, and thus great attention has been focused on BRCA1 and BRCA2 genes whose mutations lead to a high risk of developing this disease. Today, only 25% of high- and moderate-risk genes are known, suggesting the importance of the discovery of new risk modifiers.

Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer.

Angiogenesis leads to the formation of blood vessels from pre-existing ones, allowing tumor growth. Vascular endothelial growth factor (VEGF) and Angiopoietins (Ang-1, Ang-2) have a pivotal role in tumor angiogenesis but few data regarding their role in hereditary breast cancer are available. The aim of the present study was to analyze Ang-1, Ang-2, tyrosine-protein kinase receptor Tie2 and VEGF expression and their correlation in a cohort of familial and sporadic breast cancers in order to verify whether the presence of germline mutations in BRCA may have a role in tumor microenvironment regulation.

Oncosuppressor methylation: a possible key role in colon metastatic progression.

K-RAS and BRAF gene mutations are mandatory to set anti-EGFR therapy in metastatic colorectal cancer (mCRC) patients. Due to the relationship of these mutations with tumor epigenotype, we hypothesized the potential role of oncosuppressor methylation of genes involved in K-RAS/BRAF pathway (CDKN2A, RASSF1A, and RARbeta suppressor genes) in inhibiting EGFR signaling cascade. Primary tumor and synchronous liver metastatic tissues of 75 mCRC patients were characterized for promoter methylation by QMSP and for K-RAS and BRAF mutations.

Mutations and polymorphic BRCA variants transmission in breast cancer familial members.

We previously showed that about 80% of breast cancer patients at high risk to carry mutation in BRCA genes presented at least one polymorphism in these genes which resulted potentially harmful by in silico analysis. In the present paper, the genealogic transmission of those polymorphic coding and noncoding variants of BRCA genes in family's members has been investigated. Thirty families, enrolled within the Genetic Counselling Program of our Institute, with probands and at least one-first degree relative (n = 67 family members) available, have been studied for both BRCA1 and BRCA2 pathological mutation and polymorphic variants' transmission.

Circulating hTERT DNA in early breast cancer.

Background: The objective of the study was to quantify the human telomerase reverse transcriptase (hTERT) gene in the circulating DNA of patients with primary breast cancer (BC) and to test its correlation with clinical parameters of the disease.

Patients And Methods: One hundred and twenty-one BC patients, 30 patients with fibroadenoma (NBC) and 50 healthy women were enrolled.

Results: The level of hTERT in the plasma was significantly different in BC, NBC and controls (p<0.