Deciphering the Tumor Microenvironment in Prostate Cancer: A Focus on the Stromal Component.

Prostate cancer progression is significantly affected by its tumor microenvironment, in which mesenchymal cells play a crucial role. Stromal cells are modified by cancer mutations, response to androgens, and lineage plasticity, and in turn, engage with epithelial tumor cells via a complex array of signaling pathways and ligand-receptor interactions, ultimately affecting tumor growth, immune interaction, and response to therapy. The metabolic rewiring and interplay in the microenvironment play an additional role in affecting the growth and progression of prostate cancer.

Fibrin associated large B-cell lymphoma accidentally identified in a breast implant capsule: a molecular report of a rare entity.

Breast implant-associated (BIA) lymphoma is a rare malignancy, typically originating from T-cells; however, few cases of diffuse large B-cell lymphoma (LBCL) have been recently described. These cases share major features: Epstein-Barr virus positivity and a favorable prognosis with surgical intervention alone, hinting at a potential link to fibrin-associated LBCL (FA-LBCL). This study presents the first case of BIA-FA-LBCL in Italy and one of the few assessed from a molecular standpoint so far.

Gene Signature for Predicting Metastasis in Prostate Cancer Using Primary Tumor Expression Profiles.

Unlabelled: Prostate cancer (PCa) is currently the most commonly diagnosed cancer and second leading cause of cancer-related death in men in the United States. The development of metastases is associated with a poor prognosis in PCa patients. Since current clinicopathological classification schemes are unable to accurately prognosticate the risk of metastasis for those diagnosed with localized PCa, there is a pressing need for precise and easily attainable biomarkers of metastatic risk in these patients.

Blocking lipid synthesis induces DNA damage in prostate cancer and increases cell death caused by PARP inhibition.

Androgen deprivation therapy (ADT) is the primary treatment for prostate cancer; however, resistance to ADT invariably develops, leading to castration-resistant prostate cancer (CRPC). Prostate cancer progression is marked by increased de novo synthesis of fatty acids due to overexpression of fatty acid synthase (FASN), making this enzyme a therapeutic target for prostate cancer. Inhibition of FASN results in increased intracellular amounts of ceramides and sphingomyelin, leading to DNA damage through the formation of DNA double-strand breaks and cell death.

Cell-Free DNA: Unveiling the Future of Cancer Diagnostics and Monitoring.

As we conclude this Special Issue of 21 published articles dedicated to cell-free DNA (cfDNA) as a prognostic and predictive biomarker in solid cancers, we find ourselves gazing at a vibrant landscape of research on cfDNA [...

Distinct mesenchymal cell states mediate prostate cancer progression.

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species.

Think "HER2" different: integrative diagnostic approaches for HER2-low breast cancer.

This work explores the complex field of HER2 testing in the HER2-low breast cancer era, with a focus on methodological aspects. We aim to propose clear positions to scientific societies, institutions, pathologists, and oncologists to guide and shape the appropriate diagnostic strategies for HER2-low breast cancer. The fundamental question at hand is whether the necessary tools to effectively translate our knowledge about HER2 into practical diagnostic schemes for the lower spectrum of expression are available.

Pre-Implantation Kidney Biopsies in Extended Criteria Donors: From On Call to Expert Pathologist, from Conventional Microscope to Digital Pathology.

The number of patients awaiting a kidney transplant is constantly rising but lack of organs leads kidneys from extended criteria donors (ECD) to be used to increase the donor pool. Pre-transplant biopsies are routinely evaluated through the Karpinski-Remuzzi score but consensus on its correlation with graft survival is controversial. This study aims to test a new diagnostic model relying on digital pathology to evaluate pre-transplant biopsies and to correlate it with graft outcomes.

Notch-based gene signature for predicting the response to neoadjuvant chemotherapy in triple-negative breast cancer.

Background: While the efficacy of neoadjuvant chemotherapy (NACT) in treating triple-negative breast cancer (TNBC) is generally accepted, not all patients derive benefit from this preoperative treatment. Presently, there are no validated biomarkers to predict the NACT response, and previous attempts to develop predictive classifiers based on gene expression data have not demonstrated clinical utility. However, predictive models incorporating biological constraints have shown increased robustness and improved performance compared to agnostic classifiers.

Advancing the PD-L1 CPS test in metastatic TNBC: Insights from pathologists and findings from a nationwide survey.

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists.

Value of Artificial Intelligence in Evaluating Lymph Node Metastases.

One of the most relevant prognostic factors in cancer staging is the presence of lymph node (LN) metastasis. Evaluating lymph nodes for the presence of metastatic cancerous cells can be a lengthy, monotonous, and error-prone process. Owing to digital pathology, artificial intelligence (AI) applied to whole slide images (WSIs) of lymph nodes can be exploited for the automatic detection of metastatic tissue.

Distinct mesenchymal cell states mediate prostate cancer progression.

Alterations in tumor stroma influence prostate cancer progression and metastatic potential. However, the molecular underpinnings of this stromal-epithelial crosstalk are largely unknown. Here, we compare mesenchymal cells from four genetically engineered mouse models (GEMMs) of prostate cancer representing different stages of the disease to their wild-type (WT) counterparts by single-cell RNA sequencing (scRNA-seq) and, ultimately, to human tumors with comparable genotypes.

Standard Operating Procedures (SOPs) for non-invasive multiple biomarkers detection in an academic setting: A critical review of the literature for the RENOVATE study protocol.

Liquid biopsy has the potential to drastically change clinical practice, paving the way to a novel non-invasive approach for cancer diagnosis and treatment. One of the limitations for the implementation of liquid biopsy in clinical practice is the lack of shared and reproducible standard operating procedures (SOPs) for sample collection, processing and storage. Here, we present a critical review of the literature focusing on the available SOPs to guide liquid biopsy management in research settings and describe SOPs that our laboratory developed and employed in the context of a prospective clinical-translational trial (RENOVATE, NCT04781062).

The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw.

Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated.

Epidemiology of Merkel cell carcinoma in Tuscany (Italy), 2006-2021.

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that still has a poor prognosis. MCC incidence has increased in recent years worldwide. The aim of our study was to perform an epidemiological retrospective study and to evaluate the impact of MCC clinical and pathological features on overall survival (OS) in a specific geographical area.

Cervical Adenocarcinoma: A Still Under-investigated Malignancy.

Background/aim: The aim of the study was to correlate the expression of mismatch repairs proteins (MMR), programmed-death-ligand1 (PDL-1), and estro-progestinic receptors (ER/PgR) in tissue samples from a series of cervical adenocarcinoma (ADC) patients with their clinicopathological features.

Materials And Methods: Thirty-nine ADC specimens were retrospectively retrieved from the Division of Pathology of the University Hospital of Pisa from 2015 to 2021. Histological subtype, grade (G), Silva pattern, presence of lymph vascular space invasion (LVI), and perineural invasion (PNI) were annotated.

The Prostate Stromal Transcriptome in Aggressive and Lethal Prostate Cancer.

Prostate cancer has a heterogeneous prognosis. Most previous studies have focused on the identification of prognostic biomarkers in the prostate cancer tumor. However, it is increasingly recognized that the tumor microenvironment contributes to prostate cancer aggressiveness and progression.

Circulating Cell-Free DNA in Renal Cell Carcinoma: The New Era of Precision Medicine.

Tumor biopsy is still the gold standard for diagnosing and prognosis renal cell carcinoma (RCC). However, its invasiveness, costs, and inability to accurately picture tumor heterogeneity represent major limitations to this procedure. Analysis of circulating cell-free DNA (cfDNA) is a non-invasive cost-effective technique that has the potential to ease cancer detection and prognosis.

Old and New Systemic Immune-Inflammation Indexes Are Associated with Overall Survival of Glioblastoma Patients Treated with Radio-Chemotherapy.

. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. .

Pyruvate Kinase M1 Suppresses Development and Progression of Prostate Adenocarcinoma.

Differential expression of PKM1 and PKM2 impacts prostate tumorigenesis and suggests a potential therapeutic vulnerability in prostate cancer.

Is It Time to Consider the Androgen Receptor as a Therapeutic Target in Breast Cancer?

Breast Cancer (BC) is a heterogeneous disease and the most prevalent malignant tumor in women worldwide. The majority of BC cases are positive for Estrogen Receptor (ER) and Progesterone Receptor (PgR), both known to be involved in cancer pathogenesis, progression, and invasion. In line with this, hormonal deprivation therapy appears to be a useful tool and an effective treatment for these BC subtypes.

Immunohistochemistry for Thymidine Kinase-1 (TK1): A Potential Tool for the Prognostic Stratification of Breast Cancer Patients.

Breast cancer (BC) is the most frequent non-cutaneous malignancy in women. Histological grade, expression of estrogen and progesterone receptors (ER and PgR), overexpression/amplification of the human epidermal growth factor receptor 2 (HER2) oncogene, and proliferative activity measured with ki-67 provide important information on the biological features of BC and guide treatment choices. However, a biomarker that allows a more accurate prognostic stratification is still lacking.