The cDNA microarray gene profile of gastrointestinal stromal tumors (GISTs) revealed that DOG1 (TMEM16A) gene was mostly expressed in these neoplasms. Immunohistochemically, DOG1 protein was found positive in a significant proportion of GISTs. However, normal tissues' expression of DOG1 is not yet completely studied. Our study intended to identify the DOG1 protein expression in normal adult and fetal tissues, in comparison with that of GISTs, using an anti-DOG1 polyclonal serum. Fourteen CD117/CD34-positive GIST cases were tested for DOG1. Tissue samples from autopsies of 15 human fetuses and 11 adults were tested immunohistochemically on simple or double staining with antibodies raised against: DOG1, insulin, glucagon, somatostatin, NK1, PGP9.5, chromogranin A, and synaptophysin. All the tested GISTs were positive for DOG1, with a membranous and cytoplasmic location. The normal tissues showed a distinct positivity for DOG1 only in the endocrine pancreas, in both fetal and adult ones. The other tissues tested showed a weak or negative reaction. The DOG1 staining pattern in the pancreas islets was granular, like that of neuroendocrine markers. The location of DOG1 expression in pancreatic islets was partly similar to neuroendocrine markers chromogranin A, PGP9.5, and synaptophysin. The positive cells were situated centrally, in the vicinity of insulin-bearing cells as seen on double staining. DOG1 positivity in fetal and adult pancreatic islets suggests the strong antibody affinity for neuroendocrine cells. Before making a final conclusion regarding the suitability of DOG1 as a new neuroendocrine marker, a large survey of neuroendocrine lesions must be undertaken, including carcinoid tumors of various sites and pancreatic endocrine tumors. To the best of our knowledge, this particular localization has not been reported yet for DOG1.

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their “mosaic” CDX2 expression pattern.

Lung cancer ranks second worldwide after breast cancer and third in Europe after breast and colorectal cancers when both sexes and all ages are considered. In this context, the aim of this study was to emphasize the power of dual analysis of the molecular profile both in tumor tissue and plasma by NGS assay as a liquid biopsy approach with impact on prognosis and therapy modulation in NSCLC patients. NGS analysis was performed both from tissue biopsies and from cfNAs isolated from peripheral blood samples. Out of all 29 different mutations detectable by both NGS panels (plasma and tumor tissue), seven different variants (24.13%; EGFR L858R in two patients, KRAS G13D and Q61H and TP53 G244D, V197M, R213P, and R273H) were detected only in plasma and not in the tumor itself. These mutations were detected in seven different patients, two of them having known distant organ metastasis. Our data show that NGS analysis of cfDNA could identify actionable mutations in advanced NSCLC and, therefore, this analysis could be used to monitor the disease progression and the treatment response and even to modulate the therapy in real time.

Background/Objective: Breast cancer (BC) management has traditionally relied on static clinicopathologic and immunohistochemical biomarkers (hormone receptor status, HER2 expression, and proliferative activity assessed at diagnosis). However, these biomarkers are typically evaluated at a single time point and may not reflect therapy-induced molecular evolution. This study evaluates whether longitudinal molecular profiling before and after treatment better characterizes tumor dynamics and provides clinically actionable insights into treatment response, resistance, and prognosis. Methods: Thirty-two patients with invasive breast carcinoma were analyzed using histopathology, immunohistochemistry, tissue-based next-generation sequencing, and plasma circulating tumor DNA (ctDNA) analysis. Paired tumor tissue and plasma samples were collected before and after treatment when available. Changes in biomarker expression, molecular subtype, and genomic alterations were assessed to characterize molecular plasticity under therapeutic pressure. Results: The cohort had a median age of 54 years (range 29–86), predominantly invasive ductal carcinoma (>85%), and high-grade disease. Hormone receptor-positive tumors accounted for 78.1%. Molecular subtypes were Luminal A (34.4%), Luminal B HER2− (40.6%), Luminal B HER2+ (6.3%), HER2-enriched (6.3%), and triple-negative breast cancer (12.5%). Initial tissue sequencing identified PI3K/AKT pathway alterations in 28.1% of cases. Post-treatment analyses revealed substantial molecular discordance, including progesterone receptor loss (33.3%), HER2 status changes (33.3%), and Ki67 variability (77.8%). Plasma ctDNA analysis was informative in 53.1% of patients and identified additional clinically relevant alterations, including FGFR1 amplification and BRCA1/2 variants not detected in tissue. Conclusions: BC molecular profiles are dynamic and frequently altered by therapy. Longitudinal molecular assessment reveals clinically actionable changes overlooked by static subtyping, supporting a dynamic model of molecular classification, highlighting the potential value of adaptive molecular subtyping to improve treatment stratification and resistance monitoring.

Backgound/Objective: Breast cancer (BC) management has traditionally relied on static clinicopathologic and immunohistochemical biomarkers (hormone receptor status, HER2 expression, and proliferative activity assessed at diagnosis. However, these biomarkers are typically evaluated at a single time point and may not reflect therapy-induced mo-lecular evolution. This study evaluates whether longitudinal molecular profiling before and after treatment better characterizes tumor dynamics and provides clinically ac-tionable insights into treatment response, resistance, and prognosis. Methods: Thirty-two patients with invasive breast carcinoma were analyzed using his-topathology, immunohistochemistry, tissue-based next-generation sequencing, and plasma circulating tumor DNA (ctDNA) analysis. Paired tumor tissue and plasma sam-ples were collected before and after treatment when available. Changes in biomarker expression, molecular subtype, and genomic alterations were assessed to characterize molecular plasticity under therapeutic pressure. Results: The cohort had a median age of 54 years (range 29–86), predominantly invasive ductal carcinoma (>85%) and high-grade disease. Hormone receptor–positive tumors accounted for 78.1%. Molecular subtypes were Luminal A (34.4%), Luminal B HER2− (40.6%), Luminal B HER2+ (6.3%), HER2-enriched (6.3%), and triple-negative breast cancer (12.5%). Initial tissue sequencing identified PI3K/AKT pathway alterations in 28.1% of cases. Post-treatment analyses revealed substantial molecular discordance, including progesterone receptor loss (33.3%), HER2 status changes (33.3%), and Ki67 variability (77.8%). Plasma ctDNA analysis was informative in 53.1% of patients and identified additional clinically relevant alterations, including FGFR1 amplification and BRCA1/2 variants not detected in tissue. Conclusion: BC molecular profiles are dynamic and frequently altered by therapy. Longitudinal molecular assessment reveals clinically actionable changes overlooked by static subtyping, supporting a dynamic model of molecular classification, highlighting the potential value of adaptive molecular subtyping to improve treatment stratification and resistance monitoring.