Neoplastic Features Research Articles

Are Ameloblastic Fibroma-related Lesions True Tumors?: Evidence Through CNA and BRAF Mutation Analysis.

Ameloblastic fibroma (AF) and related lesions, namely ameloblastic fibrodentinoma (AFD) and ameloblastic fibro-odontoma (AFO), span a spectrum from true neoplasms to hamartomas. The 2017 World Health Organization classification proposes that AFD and AFO are precursors to odontomas, yet their precise nature remains uncertain. This study examined 19 AF cases, 4 AFD, 15 AFO, 19 odontomas (OD, 14 complex, 5 compound), and 2 ameloblastic fibrosarcomas (AFS), focusing on clinical characteristics, recurrence, and molecular profiles. AF primarily affected individuals under 20 years (60.0% of cases), mainly in the mandible (68.4%), with a recurrence rate of 21.1% in the followed cases. AFD and AFO appeared in younger patients (average age 15.7y) without any recurrence observed. Notable differences in site and size distribution were observed between AF, its related lesions, and odontomas. Copy number alterations (CNAs) were detected in the mesenchymal component in 9 of 19 AF (47.4%), 2 of 4 AFD (50.0%), 6 of 14 AFO (42.9%), and 2 of 2 AFS (100%). In contrast, all odontomas exhibited normal CNAs, highlighting the specificity of CNAs in mesenchymal elements of AF and related lesions. BRAF p.V600E mutation was identified in the mesenchymal component in 13 of 19 AF (68.4%), 2 of 4 AFD (50.0%), 8 of 15 AFO (53.3%), and 2 of 2 AFS (100%), whereas all 19 odontomas were BRAF wild type. No mutations were found in the epithelial component. Our analysis reveals that AF and its related lesions present a spectrum of biological behaviors, from true neoplasms to hamartomas. The presence of BRAF p.V600E mutations and CNAs in their mesenchymal components, as opposed to odontomas, indicates potential neoplastic characteristics. Profiling copy number alterations in AF and related lesions emerge as a valuable tool for enhancing their differential diagnosis and facilitating the anticipation of disease progression. Our findings underscore the efficacy of copy number alteration analysis in determining the nature of lesions within AF and related lesions.

Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study

BACKGROUND Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM To explore endoscopic detection and diagnostic strategies for MGCs. METHODS This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.

A case of chronic expanding hematoma mimicking a cystic pancreatic tumor

BackgroundA chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach.Case presentationWe report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space.ConclusionChronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence.

Differential network analysis reveals the key role of the ECM-receptor pathway in α-particle-induced malignant transformation

Space particle radiation is a major environmental factor in spaceflight, and it is known to cause body damage and even trigger cancer, but with unknown molecular etiologies. To examine these causes, we developed a systems biology approach by focusing on the co-expression network analysis of transcriptomics profiles obtained from single high-dose (SE) and multiple low-dose (ME) α-particle radiation exposures of BEAS-2B human bronchial epithelial cells. First, the differential network and pathway analysis based on the global network and the core modules showed that genes in the ME group had higher enrichment for the extracellular matrix (ECM)-receptor interaction pathway. Then, collagen gene COL1A1 was screened as an important gene in the ME group assessed by network parameters and an expression study of lung adenocarcinoma samples. COL1A1 was found to promote the emergence of the neoplastic characteristics of BEAS-2B cells by both in vitro experimental analyses and in vivo immunohistochemical staining. These findings suggested that the degree of malignant transformation of cells in the ME was greater than that of the SE, which may be caused by the dysregulation of the ECM-receptor pathway.

A Nanorobotics-Based Approach of Breast Cancer in the Nanotechnology Era.

We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice.

Calcifying Odontogenic Cyst Demonstrates Recurrent WNT Pathway Mutations and So-Called Adenoid Ameloblastoma-Like Histology: Evidence Supporting Its Classification as a Neoplasm

Calcifying odontogenic cyst (COC), once called calcifying cystic odontogenic tumor, is classified under the category of odontogenic cysts. However, the proliferative capacity of the lesional epithelium and consistent nuclear β-catenin expression raise questions about its current classification. This study aimed to determine whether COC would be better classified as a neoplasm in the histologic and molecular context. Eleven odontogenic lesions diagnosed as COC or calcifying cystic odontogenic tumor were included in this study. The growth patterns of the lesional epithelium were analyzed histologically in all cases. β-catenin immunohistochemistry and molecular profiling using Sanger sequencing and whole-exome sequencing were performed in 10 cases. Of the 11 cases studied, histologic features reminiscent of so-called adenoid ameloblastoma were observed in 72.7% (8/11), and small islands of clear cells extended into the wall in 36.4% (4/11). Intraluminal and/or mural epithelial proliferation was found in 72.7% of the cases (8/11). Nuclear β-catenin expression was observed focally in all 10 cases studied, mainly highlighting epithelial cells forming morules and adjacent to dentinoid. CTNNB1 hotspot mutations were detected in 60.0% of the cases (6/10). All the remaining cases had frameshift mutations in tumor-suppressor genes involved in the WNT pathway, including APC and NEDD4L. Recurrent WNT pathway mutations leading to nuclear translocation of β-catenin and distinct epithelial growth patterns found in COC are the neoplastic features shared by its solid counterpart, dentinogenic ghost cell tumor, supporting its classification as a tumor rather than a cyst.

Abstract C090: Elucidation of misp53-driven subtype specification and functions in pancreatic cancer

Abstract This study examines how mutations in the TP53 gene, specifically gain-of-function (GOF) mutations, impact the subtyping and stratification of pancreatic ductal adenocarcinoma (PDAC). In addition, it investigates the underlying mechanisms as well as the potential therapeutic implications.TP53 mutations/deletions are present in 60-75 % of cases in PDAC. The most common mutations are three specific hotspot missense mutations (misp53) found at codons R273H, R248W, and R175H. Several studies indicate that these misp53 mutants, despite losing their tumor suppressive function, acquire new oncogenic effects promoting disease aggressiveness and resistance to conventional therapies. Recent findings show that misp53 mutants are associated with a poorly differentiated metastatic subtype in PDAC. However, it is unclear how distinct misp53 mutants, such as misp53R273H, affect PDAC progression and therapy resistance and whether different mutants exert distinct functions. In this study, we explore misp53R273H- and misp53R248W-driven subtype-specificity and functions in PDAC aggressiveness by exploiting transcriptomics, genomic binding and regulation, controlled functional pathways and potential therapeutic targets. By combining cell line-based RNA- and ChIP-seq data we report that misp53R273H associates with and fuels basal-like (BL) neoplastic features by a potential regulation of cell cycle progression. Preclinical mouse models underpinned these findings by connecting misp53R273H tumors to metastatic spread. Generation of constitutive knockdown cell lines and corresponding overexpression assays could support these findings by bridging a loss of misp53R273H to the more favorable classical subtype properties. Of note, co-immunoprecipitation coupled to mass spectrometry analysis revealed misp53-specific and common hotspot mutant interaction partners: for instance, proteins of the group of chromatin remodelers or the ubiquitination pathway that could serve as a mechanistic foundation for misp53-specific functional outcomes. Further, implementation of a large-scale drug screen, flow cytometry and protein expression analyses revealed insights in the potential misp53-specific regulated pathways and therapeutic vulnerabilities, which strongly correlate to cell cycle progression and thus to the previous results. Integrating these findings with preclinical mouse studies, patient-derived xenograft cell lines and publicly available patient data sets strengthens the reported results and highlights their translational relevance. In conclusion, this study clearly demonstrates that hotspot misp53 mutants play a critical role in influencing PDAC subtype-specification and disease aggressiveness. In particular, misp53R273H was associated with BL aggressiveness and cell cycle progression. The ultimate aim of the study is to identify misp53 mutant-specific patient stratification to broaden individualized therapy options. Citation Format: Laura Urbach, Lena Wieland, Frederike Penz, Lukas Klein, Jennifer Appelhans, Christof Lenz, Carolin Schneider, Schneider Günter, Ramona Schulz-Heddergott, Volker Ellenrieder, Elisabeth Heßmann, Shiv K. Singh. Elucidation of misp53-driven subtype specification and functions in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C090.

Proto-oncogene mutations in middle ear cholesteatoma contribute to its pathogenesis

BackgroundChronic inflammation causes bone destruction in middle ear cholesteatomas (MECs). However, the causes of their neoplastic features remain unknown. The present study demonstrated for the first time that neoplastic features of MEC are based on proto-oncogene mutations.ResultsDNA was extracted from MEC and blood samples of five patients to detect somatic mutations using depth-depth exome sequencing. Exons with somatic variants were analyzed using an additional 17 MEC/blood test pairs. Variants detected in MECs but not in blood were considered pathogenic variant candidates. We analyzed the correlation between proto-oncogene (NOTCH1 and MYC) variants and the presence of bone destruction and granulation tissue formation. MYC and NOTCH1 variants were detected in two and five of the 22 samples, respectively. Two of the NOTCH1 variants were located in its specific functional domain, one was truncating and the other was a splice donor site variant. Mutations of the two genes in attic cholesteatomas (n = 14) were significantly related with bone destruction (p = 0.0148) but not with granulation tissue formation (p = 0.399).ConclusionsThis is the first study to demonstrate a relationship between neoplastic features of MEC and proto-oncogene mutations.

Rectal Polyp Prolapse: A Case Report

Colorectal adenomas are polyps that develop from the mucosa and exhibit neoplastic characteristics. Adenomas’ increasing dysplasia and malignant potential are connected to their size, villous content, and patient’s age. An anorectal emergency is definitely a possibility when there are large villous polyps in the rectum. They could be involved in rectal bleeding, blockage, prolapse, or imprisonment. We describe a 53-year-old female who was treated successfully for giant tubulovillous rectal adenoma that was prolapsed through anal opening. The patient’s clinical symptoms and signs were mistaken for prolapsed hemorrhoids.

P19.02.A FUNCTIONAL CONSEQUENCES OF IDH1 AND CIC MUTATIONS ON OLIGODENDROGLIOMA CELLS OF ORIGIN

Abstract BACKGROUND Oligodendrogliomas are primitive tumors of the central nervous system characterized by mutations in isocitrate dehydrogenase 1 (IDH1R132H) gene, codeletion of 1p and 19q chromosomic arms and mutations in Capicua (CIC) gene. Oligodendrocyte precursor cells (OPCs) are potential cells of origin for oligodendrogliomas and OPC-like tumor cells are responsible for tumor amplification at early stages of gliomagenesis. Although genetic alterations are well characterized for these tumors, little is known about the roles of IDH1 and CIC in oligodendroglioma initiation and development. Individually, IDH1 and CIC mutations can induce neoplastic characteristics but are not sufficient for tumoral development. We aim to understand how IDH1 and CIC mutations impact OPC development and whether these alterations are sufficient for tumoral initiation. METHODS We have generated an inducible mouse model allowing endogenous expression of IDH1R132H and inactivation of CIC in postnatal OPCs. We analyzed by immunofluorescence the proliferation and differentiation status of mutated oligodendroglial cells and other brain cells, at postnatal and adult stages. RESULTS We describe distinct effects of these mutations on oligodendroglial cell number and proliferation, at early and late time points. In addition, we found that IDH1R132H increases the proliferation of other brain cell types, suggesting paracrine effects of this mutation in the brain. We find no evidence of tumor in the brain of mice mutated for both IDH1 and CIC at late time points. CONCLUSION Our study describes for the first time the phenotypic impact of the combined expression of IDH1 and CIC mutations on oligodendroglial lineage cells and other brain cells, leading to a better understanding of oligodendroglioma development.

The diagnostic challenge of gastrointestinal tuberculosis mimicking colon cancer: A case report

Gastrointestinal tuberculosis (TB) accounts for 3.5% of extrapulmonary TB cases and is associated with active or inactive pulmonary TB in 76% of cases. A 53-year-old lady with no prior history of morbidity visited our hospital's department with weakness, an inability to eat, a 39°C fever, no chills, and night sweats that had been present for about six months. Additionally, a colonoscopy revealed a mamelonated mass of a stenotic character in the ascending colon, along with minor mesenteric adenitis, on computed tomography scans of the abdomen and pelvis. The obtained specimen's histological analysis revealed histiocytes and a few large cells producing granulomas without neoplastic features. The colonic biopsy's Löwenstein-Jensen medium culture revealed development of the Mycobacterium TB complex. After receiving therapy for two months with rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by four months with rifampicin and isoniazid, the patient had significantly improved. The current case serves as an example of the difficulty in diagnosing GI TB. The lack of symptoms and occasionally false-positive imaging results reinforce the necessity for increased clinical suspicion.

609 Improving Patient Counselling in Patients' With PI-RADS 3 Lesions with the Use of PSA Density, A Retrospective Study in a UK District General Hospital

Abstract Introduction NICE and EAU guidelines recommend offering prostate biopsy for patients with PI-RADS 3 lesions in a multiparametric MRI. Employing PSA density (PSAd), to further risk-stratify these patients, is a promising approach to advocate for PSA surveillance over biopsies. Here, we appraise the ability of PSAd to risk-stratify PI-RADs 3 lesions across patients who underwent a prostate biopsy. Method A retrospective analysis was performed on all patients who had a multiparametric MRI with PI-RADs 3 lesions over 2-year period Jan 2021 – Dec 2022. Patients were divided into two groups according to their PSAd value and whether they have neoplastic features on histopathology. The data was analysed using Chi-Square to determine the association between PSAd levels and cancer incidence in PI-RADS 3 lesions. Results 116 patients out of 613 had PIRADS 3 reported (19%). 83 patients had biopsies (72%). 44 was positive for neoplasia (53%) and 39 was negative (47%). 44 patients in the biopsy arm had a PSAd of <0.15 (53%). Of these patients, 27 had no neoplasia (61.4%). 39 patients had PSAd >0.15 (47%) and 12 had no neoplasia (31%). PSAd < 0.15 PI-RADS 3 lesions were significantly associated with lower occurrence of prostatic malignancy on statistical analysis. Conclusions Out of all biopsied PIRADS 3 lesions, almost half (47%) had no neoplasia. More than half of patients with PSAd <0.15 had no neoplasia. Patients with PSAD <0.15 were statistically more likely to have no neoplasia compared to patients with PSAD >0.15. This information is useful for prebiopsy risk stratification and patient counselling.

Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion

Despite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown. Using CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing. Tumorigenicity and immune evasion of organoids were monitored by allograft transplantation. Human ESCC single-cell RNA sequencing data sets were analyzed to classify patients and find subsets relevant to organoid models and immune evasion. We established 32 genetically engineered esophageal organoids and identified key genetic determinants that drive ESCC initiation. A single-cell transcriptomic analysis uncovered that Trp53, Cdkn2a, and Notch1 (PCN) triple-knockout induces neoplastic features of ESCC by generating cell lineage heterogeneity and high cell plasticity. PCN knockout also generates an immunosuppressive niche enriched with exhausted T cells and M2 macrophages via the CCL2-CCR2 axis. Mechanistically, CDKN2A inactivation transactivates CCL2 via nuclear factor-κB. Moreover, comparative single-cell transcriptomic analyses stratified patients with ESCC and identified a specific subtype recapitulating the PCN-type ESCC signatures, including the high expression of CCL2 and CD274/PD-L1. Our study unveils that loss of TP53, CDKN2A, and NOTCH1 induces esophageal neoplasia and immune evasion for ESCC initiation and proposes the CCL2 blockade as a viable option for targeting PCN-type ESCC.

Utility of narrow-band imaging with or without dual focus magnification in neoplastic prediction of small colorectal polyps: a Vietnamese experience.

Accurate neoplastic prediction can significantly decrease costs associated with pathology and unnecessary colorectal polypectomies. Narrow band imaging (NBI) and dual-focus (DF) mode are promising emerging optical technologies for recognizing neoplastic features of colorectal polyps digitally. This study aimed to clarify the clinical usefulness of NBI with and without DF assistance in the neoplastic prediction of small colorectal polyps (<10 mm). This cross-sectional study included 530 small colorectal polyps from 343 consecutive patients who underwent colonoscopy at the University Medical Center from September 2020 to May 2021. Each polyp was endoscopically diagnosed in three successive steps using white-light endoscopy (WLE), NBI, and NBI-DF and retrieved for histopathological assessment. The diagnostic accuracy of each modality was evaluated with reference to histopathology. There were 295 neoplastic polyps and 235 non-neoplastic polyps. The overall accuracies of WLE, WLE+NBI, and WLE+NBI+NBI-DF in the neoplastic prediction of colorectal polyps were 70.8%, 87.4%, and 90.8%, respectively (p<0.001). The accuracy of WLE+NBI+NBI-DF was significantly higher than that of WLE+NBI in the polyp size ≤5 mm subgroup (87.3% vs. 90.1%, p<0.001). NBI improved the real-time neoplastic prediction of small colorectal polyps. The DF mode was especially useful in polyps ≤5 mm in size.

Resection of Skin Cancer Resulting in Free Vascularized Tissue Reconstruction: Always a Therapeutic Failure?

The globally increasing incidence of cutaneous malignancies leads, in parallel, to increasing numbers of locally advanced skin cancer resulting in reconstructive surgery. Reasons for locally advanced skin cancer may be a patient's neglect or aggressive tumor growth, such as desmoplastic growth or perineural invasion. This study investigates characteristics of cutaneous malignancies requiring microsurgical reconstruction with the aim of identifying possible pitfalls and improving diagnostic and therapeutic processes. A retrospective data analysis from 2015 to 2020 was conducted. Seventeen patients (n = 17) were included. The mean age at reconstructive surgery was 68.5 (±13) years. The majority of patients (14/17, 82%) presented with recurrent skin cancer. The most common histological entity was squamous cell carcinoma (10/17, 59%). All neoplasms showed at least one of the following histopathological characteristics: desmoplastic growth (12/17, 71%), perineural invasion (6/17, 35%), or tumor thickness of at least 6 mm (9/17, 53%). The mean number of surgical resections until cancer-free resection margins (R0) were achieved was 2.4 (±0.7). The local recurrence rate and the rate of distant metastases were 36%. Identified high-risk neoplastic characteristics, such as desmoplastic growth, perineural invasion, and a tumor depth of at least 6 mm, require a more extensive surgical treatment without concerns about defect size.

Dual roles of TRIM3 in colorectal cancer by retaining p53 in the cytoplasm to decrease its nuclear expression

Colorectal cancer is a very heterogeneous disease caused by the interaction of genetic and environmental factors. P53, as a frequent mutation gene, plays a critical role in the adenoma-carcinoma transition during the tumorous pathological process. Our team discovered TRIM3 as a tumor-associated gene in CRC by high-content screening techniques. TRIM3 demonstrated both tumor-suppressive and tumorigenic features in cell experiments dependent on the cell status of wild or mutant p53. TRIM3 could directly interact with the C terminus of p53 (residues 320 to 393), a common segment of wtp53 and mutp53. Moreover, TRIM3 could exert different neoplastic features by retaining p53 in the cytoplasm to decrease its nuclear expression in a wtp53 or mutp53-dependent pathway. Chemotherapy resistance develops in nearly all patients with advanced CRC and seriously limits the therapeutic efficacies of anticancer drugs. TRIM3 could reverse the chemotherapy resistance of oxaliplatin in mutp53 CRC cells by degradation of mutp53 in the nuclei to downregulate the multidrug resistance gene. Therefore, TRIM3 could be a potential therapeutic strategy to improve the survival of CRC patients with mutp53.

IGHG1 promotes malignant progression in breast cancer cells through the regulation of AKT and VEGF signaling.

Immunoglobulin heavy constant chain gamma 1 (IGHG1) is highly expressed in a variety of cancers and is considered an emerging prognostic marker. Overexpression of IGHG1 in breast cancer tissues has also been demonstrated, but an in-depth analysis of its role in disease progression has not been explored. In this study, we used a range of molecular and cell-based assays to show that increased expression of IGHG1 in breast cancer cells activates AKT and vascular endothelial growth factor (VEGF) signaling, leading to enhanced cell proliferation, invasion, and angiogenesis. We further showed that IGHG1-silencing can suppress the neoplastic characteristics of breast cancer cells in vitro and suppresses tumor growth in nude mice. These data reveal a key role of IGHG1 in the malignant progression of breast cancer cells and highlight its potential as a prognostic marker and therapeutic target to control metastasis and angiogenesis in malignant breast tissue.

Role of advanced imaging techniques in the evaluation of oncological therapies in patients with colorectal liver metastases.

In patients with colorectal liver metastasis (CRLMs) unsuitable for surgery, oncological treatments, such as chemotherapy and targeted agents, can be performed. Cross-sectional imaging [computed tomography (CT), magnetic resonance imaging (MRI), 18-fluorodexoyglucose positron emission tomography with CT/MRI] evaluates the response of CRLMs to therapy, using post-treatment lesion shrinkage as a qualitative imaging parameter. This point is critical because the risk of toxicity induced by oncological treatments is not always balanced by an effective response to them. Consequently, there is a pressing need to define biomarkers that can predict treatment responses and estimate the likelihood of drug resistance in individual patients. Advanced quantitative imaging (diffusion-weighted imaging, perfusion imaging, molecular imaging) allows the in vivo evaluation of specific biological tissue features described as quantitative parameters. Furthermore, radiomics can represent large amounts of numerical and statistical information buried inside cross-sectional images as quantitative parameters. As a result, parametric analysis (PA) translates the numerical data contained in the voxels of each image into quantitative parameters representative of peculiar neoplastic features such as perfusion, structural heterogeneity, cellularity, oxygenation, and glucose consumption. PA could be a potentially useful imaging marker for predicting CRLMs treatment response. This review describes the role of PA applied to cross-sectional imaging in predicting the response to oncological therapies in patients with CRLMs.

Schwannoma: A surgical epidemiology.

To identify the surgical incidence and prevalence of schwannoma in our region and quantify the demographic, surgical, neoplastic, and outcome characteristics of the patients diagnosed with schwannoma.. A retrospective cross-sectional study was conducted from January 1 to December 31, 2019. Enrolled were 32 of the highest volume neurosurgical centres in Pakistan. Patients with a histopathological diagnosis of schwannoma and radiological imaging were included in the study. Medical records were reviewed for data, and SPSS version 25 was used for statistical analysis. Patients were followed up for one year, which was the duration of the study. From 2750 patients diagnosed with brain tumours, 148 patients had schwannomas. Out of these, 84 (56.8%) patients were male, and 64 (43.2%) patients were female. The mean age of the patients was 39 ± 14 years. The socioeconomic statuses of the enrolled patients were lower in 72 (53.3%) patients, middle in 57 (42.2%) patients, and upper middle to upper in 6 (4.4%) patients. All patients underwent surgery, 14 patients received radiotherapy, and two patients received chemotherapy. In our cohort, 115 (77.7%) patients presented to public sector hospitals, with only 33 (22.3%) patients presenting to private hospitals. At the end of the study period, 60 (40.5%) patients had been lost to follow-up. Of the remaining 88 patients, 75 (85.2%) were alive. The mortality rate on a one-year follow-up was 14.8%. Schwannoma comprises a larger percentage of the brain tumours in our regions than reported in the literature. The high mortality rate is of particular concern and warrants further investigation to improve patient care and outcomes.

PATH-29. BIOLOGIC AND CLINICAL SIGNIFICANCE OF NEOPLASTIC AND MYELOID STATES IN DIFFUSE GLIOMAS

Abstract INTRODUCTION Interactions between neoplastic cell characteristics and the immune microenvironment is an important yet understudied area in diffuse gliomas. We examined this by analyzing single cell RNAseq data (n=290,738) from 35 glioma patients (in-house and GSE182109) including 24 IDH-wildtype and 11 IDH-mutant tumors at the single cell level. Cells were assigned to specific classes, including neoplastic cell states and myeloid components, based on established methods. We used these data to develop a signature matrix to deconvolve bulk RNAseq data from TCGA diffuse gliomas. RESULTS Clustering of neoplastic cells revealed 4 cell states: proneural, mesenchymal, proliferative and cancer signaling. Elevated proneural cell state was, as expected, positively correlated with IDH-mutant tumors, and elevated mesenchymal cell state was correlated with IDH wildtype tumors (both p&amp;lt; 0.01, chi-square), Among IDH-mutant tumors, 1p/19q co-deletion was associated with the proneural state. Fourteen distinct myeloid cell subtypes were identified, and among them several were enriched for either microglial or macrophage (or both) markers. We examined relationships of neoplastic cell state with myeloid cell type abundance and significant associations were identified in both IDH-mutant tumors and IDH-wildtype tumors between specific myeloid cell states and myeloid clusters. Among IDH-mutant tumors, 1p/19q-co-deletion status was positively associated with abundance of a specific microglial cell cluster but negatively associated with abundance of 3 other myeloid cell clusters, suggesting substantial microenvironmental differences based on 1p/19q status in IDH-mutant tumors. In survival analyses, a specific myeloid cluster group proved interesting, with increased abundance of this group showing improved survival in both IDH-mutant and -wildtype tumors, in a manner that was enriched in specific neoplastic cell states. Overall, results suggest specific interactions between neoplastic cell characteristics, (cell states, IDH- and 1p/19q status), with myeloid cell and highlight the need of further studies understand the biological significance of the immune cell environment in diffuse gliomas.