Epithelial Tumors Research Articles

COVID-19 in patients with thymic epithelial tumors with or without Good’s syndrome: a single-center retrospective study

IntroductionThymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good’s syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS.MethodsClinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations.ResultsOverall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher’s exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS.ConclusionsOur data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols.

Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms.

Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20mg/kg, and the remaining two groups received 250 and 500mg/kg CMEE for 2 weeks. After that, food was taken away for 24h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.

Peritoneal pseudomyxoma in a patient affected by appendicular mucocele: a case report

Pseudomyxoma peritonei (PMP) is an uncommon clinical condition, characterized by mucinous ascites, generally associated with a rupture of an epithelial neoplasm of the appendix. Some authors also use the term PMP to indicate mucinous dissemination after rupture of mucin-producing tumors of other sites (i.e. colon, ovary). Clinical presentation is variable and depends on the progressive accumulation of mucinous ascites (obstructive symptoms); weight loss, elevated Ca 19.9 and Ca 125 levels can be present. Here, we report a case of a 58-year-old patient with a history of appendicular mucocele and HCV-related hepatopathy, who accessed to the emergency department of our institute for the onset of epigastric pain associated with food vomiting for 5 days. Blood tests demonstrated a mild leukocytosis, a mild anemia (Hb 12.8 g/dL), and increased transaminases and cholestasis indices. A contrast-enhanced CT (CECT) scan was performed: a peritoneal cavity filled with a neoformation with lobulated margins and over-water density leading to multiple incisions of the hepatic and splenic parenchyma was documented. Appendix had an increased caliber (4 cm) with coprolite near its origin. Hence, the suspicion of PMP was raised and later confirmed on surgical exploration.

Expression of vascular endothelial growth factor receptor in thymic epithelial tumors

Expression of vascular endothelial growth factor receptor in thymic epithelial tumors

Digital spatial profiling of the microenvironment of muscle invasive bladder cancer

Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving a transcriptomic snapshot of a section of the tumour. However, tumour tissues are not homogeneous, but are composed of distinct compartments such as the tumour and stroma. To investigate the molecular profiles of bladder cancer, whilst also maintaining the spatial complexity of the tumours, we employed whole transcriptome Digital Spatial Profiling (DSP). With this method we generated a dataset of transcriptomic profiles of tumour epithelium, stroma, and immune infiltrate. With these data we investigate the spatial relationship of molecular subtype signatures and ligand signalling events. We find that Basal/Squamous and Classical subtypes are mostly restricted to tumour regions, while the stroma-rich subtype signatures are abundant within the stroma itself. Additionally, we identify ligand signalling events occurring between tumour, stroma, and immune infiltrate regions, such as immune infiltrate derived GPNMB, which was highly correlated with VEGFA expression within the tumour. These findings give us new insights into the diversity of MIBC at a molecular level and provide a dataset with detailed spatial information that was not available before in bladder cancer research.

Myopericytoma/myofibroma as a stromal component of mixed epithelial and stromal tumor of the kidney: A case report

Myopericytoma/myofibroma as a stromal component of mixed epithelial and stromal tumor of the kidney: A case report

Anaesthetic challenges in a rare case of renal cell carcinoma with inferior vena cava tumor thrombus extension into right atrium under cardiopulmonary bypass with deep hypothermic circulatory arrest

Renal cell carcinoma, an epithelial tumour of the kidney, is the ninth most common cancer worldwide. It is uniquely associated with tumour thrombi extending into the renal vein and inferior vena cava, while rarely extending till the right atrium. This poses challenges in intra-operative and post-operative hemodynamic management as well as perioperative cardio and neuroprotection making it a challenging case from anaesthetic point of view. We report a rare case of Right renal cell carcinoma with thrombus extension into right renal vein, inferior vena cava and right atrium. Right radical nephrectomy with en-bloc tumor-thrombus excision under cardiopulmonary bypass with deep hypothermic circulatory arrest was performed. The case was suspected to have a difficult intraoperative and postoperative course with major hemodynamic instability, neuroprotection, and cardioprotection in mind, and was managed appropriately.

INTERESTING CLINICAL CASE: ROLE OF ULTRASOUND DIAGNOSTICS IN DETECTING NEUROENDOCRINE TUMOR OF THE PANCREAS

Neuroendocrine tumors of the pancreas today occupy the second place in the prevalence of malignant epithelial tumors of the pancreas [1, p. 132]. Neuroendocrine tumors are divided according to activity into functioning and non-functioning tumors, the latter in turn have the second name “non-secreting” and are more common than functioning tumors. Non-functioning tumors are unfavorable because their growth is slow and a person does not feel symptoms for a long time, but the tumor grows to large sizes, thereby causing symptoms of compression of adjacent anatomical structures [3, p.458]. Neuroendocrine tumors are often diagnosed when they have already metastasized or reached a large size. In view of this, assessment of the tumor load requires the use of several methods of radiation diagnostics: ultrasound, computed tomography, magnetic resonance imaging [2, p.30]. This article will review clinical cases of neuroendocrine tumors using different diagnostic methods.

S100A2 upregulates GLUT1 expression to promote glycolysis in the progression of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor. Among the S100 protein family members, the imbalance of S100 calcium-binding protein A2 (S100A2) was related to the pathogenesis of several types of cancer, and S100A2 has been reported to be upregulated in the plasma of NPC patients; however, its specific role in NPC pathogenesis remains unclear. Thus, this study aims to determine the potential role of S100A2 in NPC to provide novel insights into NPC management. C666-1 and NPC/HK-1 cells were transfected with S100A2 silencing/overexpression (si/oe) constructs. For in vivo investigations, NPC/HK-1 cells were transfected with si/oe-S100A2 to induce tumor formation in nude mice. Cellular viability and apoptosis were assessed using the CCK8 assay, colony-forming assay, and flow cytometry. Glucose uptake and lactate production levels were quantified using biochemical assays. S100A2 expression was measured via RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence were performed to determine the levels of S100A2, PI3K, AKT, p-PI3K, p-AKT, GLUT1, HK-2, LDHA, and ki-67 proteins. S100A2 expression levels were significantly higher in NPC cancer tissues than in adjacent tissues. Similarly, C666-1 and NPC/HK-1 cells exhibited increased S100A2 expression, and silencing S100A2 significantly inhibited NPC cell viability, proliferation, glucose uptake, and lactate production, and induced apoptosis and decreased the protein levels of GLUT1, LDHA, and HK2 in NPC cells. Conversely, S100A2 overexpression enhanced these characteristics in NPC cells but could be mitigated by the PI3K/AKT inhibitor (LY294002). Silencing S100A2 suppressed the tumor formation of NPC/HK-1 cells, while S100A2 overexpression promoted tumor formation and could be hindered by a GLUT1 inhibitor (WZB117). S100A2 is upregulated in cancer tissues of NPC patients and was found to promote proliferation, glycolysis, and tumor formation in NPC cells through its interaction with GLUT1.

Gastric dysplastic lesions in Helicobacter pylori-naïve stomach: Foveolar-type adenoma and intestinal-type dysplasia.

Reports of Helicobacter pylori (Hp)-naïve gastric neoplasm (HpNGN) cases have been rapidly increasing due to the recent increase in the Hp-naïve population in Japan. Most HpNGNs exhibit the gastric immunophenotype and a low malignant potential regardless of histological type. Especially, foveolar-type gastric adenoma (FGA) and intestinal-type gastric dysplasia (IGD) rarely progress to invasive carcinoma. FGA is a foveolar epithelial neoplasm that occurs in the fundic gland (oxyntic gland) mucosa and is classified as the flat type or raspberry type (FGA-RA). The flat type is a large, whitish flatly elevated lesion while FGA-RA is a small reddish polyp. Genomically, the flat type is characterized by APC and KRAS gene mutations and FGA-RA by a common single nucleotide variant in the KLF4 gene. This KLF4 single-nucleotide variant reportedly induces gastric foveolar epithelial tumorigenesis and activates both cell proliferation and apoptosis, leading to its slow-growing nature. IGD consists of an intestinalized epithelial dysplasia that develops in the pyloric gland mucosa, characterized as a superficial depressed lesion surrounded by raised mucosa showing a gastritis-like appearance. Immunohistochemically, it exhibits an intestinal or gastrointestinal phenotype and, frequently, p53 overexpression. Thus, IGD shows unique characteristics in HpNGNs and a potential multistep tumorigenic process.

Extended-sleeve resection for endoluminal recurrence of B3 thymoma: does aerogenous spread really exist?

Thymomas are a variant of thymic epithelial tumours. They are considered malignant due to their tendency to local invasion and they showed lower metastatic behaviour. Distal metastasis is rare and an endobronchial mass is a rare presentation. First-line treatment for early-stage thymomas is surgery; for Masaoka-Koga stage III, neoadjuvant or adjuvant chemoradiation therapy should be considered in association with surgery after Multidisciplinary Tumour Board evaluation. We report a rare case of radical resection with type A extended-sleeve lobectomy in a 63-year-old woman who was affected by endobronchial recurrence of B3 thymoma, 31 months after complete and radical thymectomy.

Updated Outcomes of Surgical Treatment for Recurrent Thymic Tumor: A Report from the Japanese Nationwide Database.

This study aimed to analyze the surgical outcomes for recurrent thymic epithelial tumors and identify the factors associated with post-recurrence survival, using an updated Japanese nationwide database. The cohort that developed recurrence after the initial resection was extracted from an updated database of patients whose thymic epithelial tumors were treated surgically between 1991 and 2010. Furthermore, we reviewed clinicopathological and prognostic factors of re-resected cases. Post-recurrence survival outcomes and cause-specific deaths in non-re-resected cases were also reviewed. We enrolled 191 patients who underwent re-resection and 259 patients who did not. In the surgery group, more patients with early-stage disease, less aggressive World Health Organization (WHO) histological classification, initial complete resection, and shorter recurrence-free intervals were included. Non-thymic carcinoma, absence of preoperative treatment, longer recurrent-free interval, single-site recurrence, and R0-1 re-resection were all significantly favourable prognostic factors for post-recurrence survival in the surgery group, according to univariable analyses. Non-thymic carcinoma histology, longer recurrence-free interval, and R0-1 re-resection were identified as independent prognostic factors according to multivariable analysis. The post-recurrence survival of the entire cohort with R2 re-resection was significantly better than that of the non-surgery group, although it was not demonstrated that patients with thymoma who underwent R2 re-resection had significantly better post-recurrence and lower cause-specific death. R0-1 re-resection was newly identified as a prognostic factor after re-resection, in addition to non-thymic carcinoma histological classification and longer recurrence-free intervals, as documented in the initial report.

Pilot study to evaluate isolation by size of circulating tumour cells in canine oral melanoma.

Liquid biopsy for circulating tumour cell (CTC) detection is generally unexplored in veterinary medicine. Dogs with highly aggressive and heterogeneous tumours, such as oral malignant melanoma (OMM), could benefit from studies involving size-based isolation methods for CTCs, as they do not depend on specific antibodies. This pilot study aimed to detect CTCs from canine OMM using Isolation by Size of Epithelial Tumor Cells (ISET), a microfiltration methodology, followed by immunocytochemistry (ICC) with Melan-A, PNL2, and S100 antibodies. Ten canine patients diagnosed by histopathology and confirmed as OMM by immunohistochemistry were enrolled, their prognostic data was assessed, and blood samples were collected for CTC analysis. Results have shown the detection of intact cells in 9/10 patients. ICC has shown 3/9 Melan-A-positive, 3/9 PNL2-positive, and 8/9 S100-positive patients, confirming the importance of opting for a multimarker assay. A significant number of negative-stained CTCs were found, suggesting their high heterogeneity in circulation. Microemboli stained with either PNL2 or S100 were found in a patient with a high isolated cell count and advanced clinical stage. Preliminary statistical analysis shows a significant difference in CTC count between patients with and without lymph node metastasis (p < .05), which may correlate with tumour metastatic potential. However, we recommend further studies with more extensive sampling to confirm this result. This pilot study is the first report of intact CTC detection in canine OMM and the first application of ISET in veterinary medicine, opening new possibilities for liquid biopsy studies in canine OMM and other tumours.

Tumor-stroma contact ratio - a novel predictive factor for tumor response to chemoradiotherapy in locally advanced oropharyngeal cancer

The growth pattern of oropharyngeal squamous cell carcinomas (OPSCC) varies from compact tumor cell aggregates to diffusely infiltrating tumor cell-clusters. The influence of the growth pattern on local tumor control and survival has been studied mainly for surgically treated oral cavity carcinomas on a visual basis. In this study, we used multiplex immunofluorescence staining (mIF) to examine the antigens pan-cytokeratin, p16INK4a, Ki67, CD271, PD-L1, and CD8 in pretherapeutic biopsies from 86 OPSCC. We introduce Tumor-stroma contact ratio (TSC), a novel parameter, to quantify the relationship between tumor cells in contact with the stromal surface and the total number of epithelial tumor cells. mIF tumor cores were analyzed at the single-cell level, and tumor-stromal contact area was quantified using the R package "Spatstat". TSC was correlated with the visually assessed invasion pattern by two independent investigators. Furthermore, TSC was analyzed in relation to clinical parameters and patient survival data to evaluate its potential prognostic significance.Higher TSC correlated with poor response to (chemo-)radiotherapy (r = 0.3, p < 0.01), and shorter overall (OS) and progression-free (PFS) survival (median OS: 13 vs 136 months, p < 0.0001; median PFS: 5 vs 85 months, p < 0.0001). Visual categorization of growth pattern according to established criteria of tumor aggressiveness showed interobserver variability increasing with more nuanced categories (2 categories: k = 0.7, 95 %-CI: 0.55 - 0.85; 4 categories k = 0.48, 95 %-CI: 0.35 - 0.61).In conclusion, TSC is an objective and reproducible computer-based parameter to quantify tumor-stroma contact area. We demonstrate its relevance for the response of oropharyngeal carcinomas to primary (chemo-)radiotherapy.

Dose escalation and expansion results from the phase I study of F0024, a trophoblast cell-surface antigen 2 (TROP2) antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors.

e13131 Background: F0024 is an antibody-drug conjugate (ADC) targeting Trop-2, an intracellular calcium signaling transducer overexpressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. We assessed its safety and efficacy in patients with advanced solid tumors, mainly in triple negative breast cancer (TNBC). Methods: PTs with unresectable solid tumors refractory to/relapsed from standard treatment received F0024 on days 1 and 8 of 21-day treatment cycles. Primary objectives include maximum tolerated dose (MTD) identification, safety, and tolerability and secondary objectives include efficacy, pharmacokinetics, and incidence of anti-drug antibodies against F0024. Pts were eligible regardless of TROP2 level. Results: As of October 8, 2023, 62 pts were treated with≥1 dose of F0024. 21 pts were treated during dose escalation at 2.5 (n = 1), 5.0 (n = 3), 7.5 (n = 3), 10 (n = 4), 12 (n = 8), and 15 (n = 2) mg/kg and 41 pts with TNBC were treated in dose expansion at 10.0 (n = 30) and 12.0 (n = 11) mg/kg. 32 pts (51.6%) discontinued (20 (32.2%) due to disease progression per RECIST v1.1). Treatment emergent adverse events (TEAEs) regardless of causality were reported in 61 of 62 pts (98.4%; 34 pts [54.8%] experienced ≥grade 3, 9 pts [14.5%] had serious adverse events). Treatment related adverse events (TRAEs) were reported in 61 of 62 pts (98.4%; 32 pts [51.6%] experienced ≥grade 3, 4 pts [6.5%] had serious adverse events). The most common grade 3 TRAE were neutropenia (45.2%), leukopenia (33.9%), febrile neutropenia (4.8%), anemia (4.8%), and maculo-papular rash (4.8%). A total of 17 responses have been observed at the dose of 5.0 mg/kg or greater. 34 TNBC pts were dosed at 10 and 19 were dosed at 12 mg/kg with exposure to a median of 11.5 (1.0-26.0) and 4.0 (1.0-21.0) doses. 11 partial responses were achieved in 29 efficacy-evaluable TNBC pts at 10 mg/kg leading to an overall response rate (ORR) of 37.9% (95% CI 20.7% - 57.7%). The disease control rate of 10 mg/kg is 79.3% (95% CI 60.3%-92.0%). 5 escalation pts and 25 expansion pts remain on trial. Updated trial details/results will be presented. Conclusions: In this first-in-human study of F0024, treatment was generally well tolerated and MTD was not yet reached up to 12 mg/kg. F0024 demonstrated encouraging preliminary antitumor activity in heavily pretreated TNBC pts, especially in 10 and 12 mg/kg. Clinical trial information: NCT05174637 .

Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

Charting heterogeneity and spatial landscape of consensus molecular subtypes in colorectal cancer.

e15647 Background: High inter-patient heterogeneity and spatial diversity within tumors represent significant challenges to improving outcomes in colorectal cancer (CRC). Despite elucidation of consensus molecular subtypes (CMS), little progress has been made in translating this knowledge into clinical gain. Intratumoral CMS heterogeneity remains a relatively unexplored area and understanding of the interplay between subtypes holds promise for improving prognostication. We leverage spatial transcriptomics (ST) to enhance understanding of CMS heterogeneity and spatial distribution, with the goal of advancing personalized therapy through high resolution molecular sub-typing. Methods: ST using the 10x Genomics Visium platform was performed on paraffin-embedded CRC specimens for which comprehensive clinicopathological and long-term clinical outcome data were available. ST data were deconvoluted with respect to CMS single-cell RNA sequencing (scRNA-seq) data, yielding maps of CMS landscapes at a resolution of 55 microns. A pre-trained deep learning model was used to identify distinct CRC tissue classes (tumor epithelium, stroma, etc.) within H&amp;E images, enabling spatial correlation of histomorphology with CMS. Cellular composition within these CMS maps was quantified through deconvolution of six major cell types using reference scRNA-seq data. Pseudo-bulk samples were generated from the ST data to evaluate CMS behaviors and compute pathway activities. Results: 40 CRC patients were assayed using ST and H&amp;E profiling (13, 8, 14, and 5 from stages 1-4, respectively). Median follow-up was 112 months (Range 1–192). Intratumoral CMS heterogeneity was evident in all patients, with diverse CMS compositions. Using Simpson diversity index to quantify this heterogeneity, we observed significant correlation of heterogeneity with disease specific survival (DSS) (p = .03). CMS landscapes displayed spatial patterns that were distinct among tissue categories (average F1-score: testing = .92, validation = .89. Tissue categories based on deep learning from H&amp;E images). Tumors with higher levels of CMS1 or 4 were associated with worse outcome. Stratification by the composite CMS biomarker (CMS1+CMS4)/(CMS2+CMS3) yielded significant separation of the Kaplan-Meier curve for DSS (p = .018). Conclusions: This study demonstrates that CRC tumors contain significant intratumoral CMS heterogeneity that is not detectable using bulk classification methods. Spatial patterns in CMS transcriptional topographies correlate with H&amp;E-derived morphology, suggesting the potential for estimating CMS composition from histopathological features. Importantly, we show that spatially composite CMS-derived biomarkers possess strong prognostic potential. The capacity to decode CMS topographic patterns and associate these with clinical outcome offers great potential to advance personalized therapy for CRC.

Clinical and genomic characterization of sporadic medullary thyroid carcinoma in Chinese patients.

6094 Background: Medullary thyroid carcinoma (MTC) is a C-cell-derived epithelial neuroendocrine neoplasm. MTC has a low prevalence and a relatively worse prognosis compared with differentiated thyroid carcinoma. About 75% of all MTCs are sporadic. The clinicogenomic landscape of sporadic medullary thyroid carcinoma (sMTC) in the Chinese population was rarely described. Methods: Formalin-fixed paraffin-embedded (FFPE) samples and/or tumor tissues from a total of 121 sMTC patients from 22 centers were retrospectively collected and tested using a targeted 28-gene next-generation sequencing (NGS) panel (May 2022 to November 2023). Clinicopathological data, including age, gender, histological diagnoses, site, tumor size, and status of the lymph nodes and distant metastasis were reviewed. Regression analyses were performed to examine the association between the clinicogenomic characterization and pathologic features. Results: A total of 105 out of 121 sMTC were NGS-positive. The mutant genes included RET(66.9%), RAS(20.7%), BRAF(1.6%), TSHR(0.8%). The top 5 frequent mutations were RET M918T (24.8%, 30/121), HRAS Q61R (8.3%, 10/121), RET C634R (7.4%, 9/121), RET V804M (4.1%, 5/121), HRAS Q61K (4.1%, 5/121). Of the 13 co-mutations, 12 were RET mutations or co-occurrence of RET with other genetic alterations. Besides, the higher the age, the lower the probability of lymph node metastasis (OR=0.95, p=0.005). Also, patients with common RET mutations (including M918T, C634, C630, C611, C618, C620, A883F, S891 and V804) tended to have lymph node metastases (OR=5.67, p=0.016). We observed a significant positive linear relationship (Beta=2.0) between other gene mutations (non-RET mutations and non-RAS mutations) and tumor size. However, when the tumor diameter was analyzed according to whether it was greater than 1cm, we found that clinical factors such as age, sex, and gene mutation were not related to tumor size. Moreover, we did not find any association between this cutoff value of tumor size and lymph node metastases. It indicated that sMTC clinical diagnosis and treatment may consider pathologic and genomic features, not just whether the tumor size is &gt;1cm. Conclusions: Our study first provided the molecular characteristic of Chinese patients with large-scale sMTC. Analysis revealed that common RET mutations may be potential predictors of lymph node metastases. These conclusions remain to be validated in prospective large-scale cohorts.

Development and validation of an efficacy assessment platform utilizing patient-derived xenograft (PDX) models in ovarian cancer research.

e17564 Background: Ovarian cancer predominantly undergoes treatment through surgical and chemotherapeutic interventions. However, with an increasing rate of recurrence, there's a need for systemic chemotherapy. A paradigm shift towards personalized treatment is crucial with concerns escalating about chemotherapy resistance post PARP inhibitor treatment. This paper emphasizes the significance of preclinical drug evaluation platforms using Patient-Derived Xenograft (PDX) models, which resonate with the genuine characteristics of ovarian cancer tissues. Methods: The 112 epithelial ovarian patients' tumors sectioned to approximately 3 mm2 were subcutaneously transplanted into at least two female 5-week-old BALB/c nude mice. The xenograft tumors engrafted into mice from patient-derived tumors were defined as P1. After that, xenograft tumors serially engrafted into the following mice were termed P2 to P3. We collected and banked small pieces of tumor tissue from each passage of PDX tissue for performing Whole Exome Sequencing (WES) sequencing and RNA Sequencing. Results: We established 54 epithelial ovarian cancer PDX models that are stably growing. They show a ratio of 70.37% Serous, 11.11% clear cell, and 3.7% endometriod. The stage is 14.81% I/II, 61.11% III/IV, and 24.07% Recurrent. BRCA status consists of 59.26% wild type, 9.26% BRCA 1 mutation, 5.56% BRCA 2 mutation, and 11.11% BRAC VUS. We have obtained a variety of ovarian cancer PDX models and confirmed retained the histological characteristics of patients by H&amp;E staining. We validated the similarity of genomic information in patients and PDX models via WES and RNA sequencing. Conclusions: We have a stable and growing PDX model that accurately reflects the actual tissue characteristics of ovarian cancer. In the future, we plan to characterize drug response further and build new models resistant to existing anti-cancer drugs. Based on these, we will validate the efficacy of new drugs and suggest strategies to overcome cancer resistance.

70P Tumor biomarkers contribute to the clinical management of the O-RADS MRI risk stratification system in epithelial ovarian tumors

70P Tumor biomarkers contribute to the clinical management of the O-RADS MRI risk stratification system in epithelial ovarian tumors