Nina Zidar

NOTCH1 is associated with various tumors, including oral squamous cell carcinoma (OSCC), with a complex role depending on cellular contexts. Our aim was to analyze the expression of NOTCH1, several stem cell markers, and selected microRNAs in preneoplastic lesion of the oral cavity, oral epithelial dysplasia (OAD). Our study included formalin-fixed paraffin-embedded biopsy samples of 36 cases of OAD and 15 cases of normal oral mucosa. Expression of NOTCH1, stem cell markers (AGR2, KLF4, NANOG, OCT4, SOX2), and miR-27a, miR-34a, miR-128, miR-145, miR-150, and miR-335 was analyzed by quantitative PCR (qPCR). Expression of NOTCH1 protein was analyzed by immunohistochemistry. In OAD compared to normal mucosa, we found a significant increase in mRNA levels of NOTCH1, stem cell markers AGR2, NANOG, OCT4, and SOX2, and miR-150 and miR-128. NOTCH1 mRNA positively correlated with all five stem cell markers’ mRNA levels and miR-150. Immunohistochemistry showed variable expression patterns of NOTCH1 in OAD and normal mucosa. Our results support the role of NOTCH1 in early phases of OSCC development, with a potential contributory role in stemness, in association with AGR2, NANOG, OCT4, and SOX2, miR-150 and miR-128. These results support a complex role of NOTCH1 in carcinoma development, i.e., from oncogenic to tumor suppressor roles and stemness maintenance, not only in invasive OSCC but also in its precursor—OED.

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts.

Benign and malignant head and neck tumors are common worldwide and cause mortality and morbidity with variations in population prevalence

The current consensus guideline offers a comprehensive and practical guidance on the diagnostic and monitoring of patients with inflammatory bowel disease (IBD). It provides recommendations on requirements for initial diagnosis, detection of complications, the use of monitoring tools in patients with IBD and diagnostics in specific situations, such as pregnancy, postoperatively and for cancer surveillance. The guideline is a joint project of the European Crohn’s and Colitis Organization (ECCO), the European Society of Gastrointestinal and Abdominal Radiology, the European Society of Pathology, and the International Bowel Ultrasonography Group under the leadership of ECCO.

Despite decades of progress, laryngeal squamous cell carcinoma (SCC) is still associated with significant morbidity and mortality worldwide. Additional biomarkers are needed to apply precision medicine and predict the clinical course. We reviewed and summarised routinely reported histopathologic features (e.g. subtypes of laryngeal SCC) along with promising potential biomarkers not yet routinely assessed using international guidelines. These include extra- vs intratumoural vascular and perineural invasion, tumour budding, depth of invasion, and tumour-infiltrating lymphocytes. We also address the problem of specimen quality and type (open approach vs endoscopic surgery) and the related limitations. High-risk human papillomavirus infection is another controversial issue to be discussed, being rare in laryngeal SCC, with an indeterminate prognostic significance and less reliable p16 overexpression as a surrogate marker of HPV infection. Further studies are warranted to address the applicability and to see which of the described parameters may help to better stratify patients with laryngeal SCC and should therefore be included in the pathology report.

Background/Objectives: Gastric intestinal metaplasia (GIM) is considered an irreversible preneoplastic precursor for gastric adenocarcinoma in adults. However, its significance in children and the long-term outcome remain poorly understood. Methods: All children diagnosed with GIM between 2000 and 2020 were identified at a large tertiary referral centre. Upon reaching adulthood (≥18 years), the patients were invited to undergo follow-up esophagogastroduodenoscopy (using narrow-band imaging additionally to high-definition white light endoscopy), with gastric biopsies obtained according to the updated Sydney protocol. Childhood and adulthood gastric biopsies were re-evaluated by two experienced gastrointestinal pathologists using Kreyberg staining. Results: Paediatric GIM was diagnosed in 178/14,409 (1.2%) esophagogastroduodenoscopies performed during the study period. Fifty adult patients with childhood GIM agreed to participate in the study. The mean age at childhood and adulthood endoscopies were 14.3 years (median 15) and 25.2 years (median 24), respectively. The mean follow-up interval was 10.5 years. All childhood GIM cases were classified as complete-type. Notably, GIM completely resolved in 41/50 of patients (82%) by the time of adulthood follow-up. No dysplasia or carcinoma was detected in any patient. Childhood Helicobacter pylori infection, similar to other evaluated host-related factors, was not significantly associated with the persistence of GIM into adulthood (11.2% vs. 29.3%, p = 0.41). Conclusions: Childhood GIM was a rare finding but demonstrated a high rate of reversibility by adulthood regardless of Helicobacter pylori status, with no cases of dysplasia or carcinoma observed during long-term follow-up.

Background/Objectives: Gastric and lung adenocarcinomas are among the most common adenocarcinomas worldwide. Our research aimed to validate methylation biomarkers that differentiate gastric and lung adenocarcinomas from hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma and paired healthy tissues. Methods: The study analyzed 178 formalin-fixed, paraffin-embedded tissue samples, including 14 gastric adenocarcinomas, 15 lung adenocarcinomas, 15 hepatocellular carcinomas, 15 cholangiocarcinomas, 15 colorectal carcinomas, 15 pancreatic adenocarcinomas and their paired healthy tissues. Methylation status was determined experimentally by methylation-sensitive high resolution melting. The diagnostic panels were validated on bioinformatics datasets from The Cancer Genome Atlas and Gene Expression Omnibus, comprising 1981 and 773 samples, respectively. Sensitivity, specificity, diagnostic accuracy and predictive values for each cancer type were calculated for the experimental, Gene Expression Omnibus and The Cancer Genome Atlas datasets. Results: The gastric cancer-specific panel showed a sensitivity of 78.6–83.9%, a specificity of 86.6–94.6% and a diagnostic accuracy of 89.9–96.1% to differentiate between all tumors, and a sensitivity of 78.6–83.9%, a specificity of 89.2–96.4% and a diagnostic accuracy of 88–96.1% to differentiate between all tumors and healthy tissues. The lung adenocarcinoma-specific panel showed a sensitivity of 61.1–93.3%, a specificity of 70.3–90.8% and a diagnostic accuracy of 74.2–90.6% to differentiate between all tumors, and a sensitivity of 61.1–93.3%, a specificity of 77.9–93.4% and a diagnostic accuracy of 79.2% to 93.1% to differentiate between all tumors and healthy tissues. Conclusions: This study demonstrates the potential of using diagnostic methylation panels to differentiate gastric and lung adenocarcinomas from other common adenocarcinomas and paired healthy tissues.