Local Lymph Node Metastasis Research Articles

Relative Tumour Volume in Canine Oral Melanoma Staging and Prognosis.

Melanoma is one of the most common canine oral malignant tumours and is highly aggressive and metastatic, even at the early stages of development. Surgery relies on wide excision of the primary tumour and regional lymphadenectomy, with or without adjuvant therapy. Tumour location and size are important when considering staging, which ultimately affects the curative intent of surgery. Nevertheless, absolute tumour volume (TV) is not related to the vast phenotypic variability within canine breeds. This study aimed to determine the cutoff values of two ratios-tumour-to-head volume (THR) and tumour-to-body volume (TBR)-and assess whether they could be associated with the odds of finding metastasis at presentation and/or the likelihood of achieving tumour-free excision margins. A retrospective case series involving 51 dogs was used to evaluate the preoperative head/neck and chest computed tomography and histopathology of the primary mass and excised lymph nodes. Higher TV, THR% and TBR% values were associated with bone lysis and mitotic count (MC). The Ki67 index was significantly associated with local and distant metastases at presentation, whereas MC was associated with local metastasis alone. Tumour-infiltrated surgical margins were associated with caudally located tumours, regardless of the tumour size. Dogs with lymph node metastasis at presentation were seven times more prone to have local relapse. TV, THR% and TBR% values were positively associated with local lymph node metastasis at presentation. Cutoff values for both TV and TBR% were proposed to predict lymph node metastasis at presentation (TV = 6.423 cm3 and TBR% = 0.043), being supported by post-surgical survival analysis.

Radiographs are of limited use and low cost-effectiveness when combined with ultrasound for abdominal restaging in dogs with solid, soft tissue tumours.

The purposes of this study were to assess the frequency of detection of clinically relevant findings by abdominal radiographs and abdominal ultrasound during restaging of solid, soft tissue tumours in dogs and to determine the cost per clinically relevant finding for both modalities. The medical records of 159 dogs which underwent a total of 223 restaging episodes following a diagnosis of a solid, soft tissue tumour within, or with potential for metastasis to, the abdomen were reviewed. Data collected from the sample dogs were reviewed for clinically relevant findings, including local recurrence, lymph node or intra-abdominal metastasis, and other changes that would influence prognosis or management. The clinically relevant findings were compared between abdominal radiographs and abdominal ultrasound. The cost per clinically relevant finding was calculated per modality based on current hospital costs. Clinically relevant findings were observed in 158 restaging episodes. Ninety-two clinically relevant findings were detected with ultrasound alone, and 65 clinically relevant findings were detected with a combination of both modalities. Only one dog had a clinically relevant finding detected with radiographs alone. Findings were identified significantly more frequently with ultrasound than radiographs. Cost per clinically relevant finding was 495 USD (approx. 373 GBP/448 EUR) for abdominal radiographs and 323 USD (approx. 242 GBP/292 EUR) for abdominal ultrasound. Abdominal radiographs were of minimal use beyond abdominal ultrasound for restaging in this study, despite a higher cost per clinically relevant finding than abdominal ultrasound. This study does not support routine use of abdominal radiographs during routine restaging of solid, soft tissue tumours.

Comparison of clinical, hormonal, pathological and treatment outcomes of ectopic Cushing's syndrome by sex: results of a multicenter study.

To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing's syndrome (ECS) by sex. Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated. 28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar. While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.

349. CLINICAL CHARACTERISTICS AND PROGNOSTIC FACTORS OF ESOPHAGEAL SPINDLE CELL CARCINOMA

Abstract Background Esophageal spindle cell carcinoma (ESpCC) is a malignant tumor composed of sarcomatous components. ESpCC is treated as a squamous cell carcinoma. However, because ESpCC is a rare tumor, little is known regarding its clinical characteristics and prognosis. Objective This article was to discuss the clinical characteristics, treatment and prognostic factors of ESpCC. Methods All the clinical and pathological data of 25 cases of ESpCC were retrospectively analyzed. Results The sex ratio of male vs female was 2.12:1. The male median age was 55 years, and the female median age was 62 years. A total of 25 cases were performed pathological biopsy and the accuracy was 48%. The most common site for ESpCC was the middle segment of the esophagus (60%). The most common gross tumor type of ESpCC was intraluminal type (40%). The local lymph node metastasis rate was 24%. Three-year and five-year survival rates after operation were 68% and 44%, respectively. Single factor analysis showed that the N stage, T stage, pTNM stage were the facors influencing the prognosis (P<0.05). Conclusion ESpCC predominantly occurs in males and in the middle segment of the esophagus, and with a higher misdiagnosis before operation and good prognosis after operation. The intraluminal type is the most common gross tumor type. Radical operation is the preferred treatment for ESpCC. Key words Esophagus, Spindle cell carcinoma, survival analysis

Effectiveness and outcomes of endoscopic resection for superficial pharyngeal squamous cell carcinomas.

With the development of endoscopic imaging, superficial pharyngeal squamous cell carcinoma can now be detected during routine endoscopy. Recently, the effectiveness of endoscopic resection for superficial pharyngeal squamous cell carcinoma have been reported. This study had a retrospective single-center design that included patients with superficial pharyngeal squamous cell carcinoma who underwent endoscopic resection. A total 47 patients with 53 lesions were analyzed. En bloc and R0 resection rates were 83.0% and 56.6%. Local recurrence and cervical lymph node metastasis (CLNM) were detected in 1 and 3 patients during follow-up. The macroscopic type 0-I was an independent factor for CLNM. The 3-year cumulative incidence of metachronous pharyngeal squamous cell carcinoma following endoscopic resection was 33.0%, and the 5-year overall survival rate was 89.2%. Endoscopic resection is an effective treatment for superficial pharyngeal squamous cell carcinomas, and the macroscopic type 0-I is a useful predictor of CLNM.

Genetic variants of LncRNAs HOTTIP and MEG3 influence nasopharyngeal carcinoma susceptibility and clinicopathologic characteristics in the Southern Chinese population

ObjectiveRecent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC.MethodsThis research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics.ResultsIn comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers.ConclusionIndividuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3.

Role of Pathologic Single-Nodal and Multiple-Nodal Descriptors in Resected Non-Small Cell Lung Cancer

BackgroundThe 8th edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single- and multiple-N descriptors. Research QuestionDo the single- and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and MethodsUsing the National Cancer Database, we analyzed patients with pathologically staged N1–2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pSingle-N2, and pMulti-N2. Survival analysis was performed using Kaplan–Meier method and multivariate Cox regression models. ResultsIn the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 NSCLC patients had pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2, respectively. Patients with pMulti-N1 and pMulti-N2 had a shorter survival than those with pSingle-N1 and pSingle-N2, respectively (hazard ratio [HR]: 1.22, P < 0.0001 for N1 and 1.39, P < 0.0001 for N2). After adjusting age, sex, and histology, the HR for pSingle-N2 compared with pMulti-N1 was 1.05 (P = 0.0031). Patients with pN1 were categorized by metastatic lymph node count (1, 2, 3, 4+), showing significant prognostic differences among groups (P < 0.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy or more, survival ≥ 30 days, ≥ 10 examined lymph nodes, and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708) analyses supported these results. InterpretationNSCLC patients with 1 metastatic lymph node, whether in N1 or N2 stations, had better survival than those with more than 1 lymph node involved. NSCLC patients with a single skip N2 lymph node metastasis had survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to ≥ 4 was sequentially prognostic.

Implicating clinical utility of altered expression of PTCH1 & SMO in oral squamous cell carcinoma.

Oral cancer poses a significant burden on public health in India, with higher incidence and mortality rates. Despite advancements in treatment modalities, prognosis remains poor due to factors such as localized recurrence and lymph node metastasis, potentially influenced by cancer stem cells. Among signaling pathways implicated in CSC regulation, the Hedgehog pathway plays a crucial role in oral squamous cell carcinoma (OSCC). 97 OSCC patients' tissue samples were collected and subjected to RNA isolation, cDNA synthesis and quantitative real-time PCR to analyze PTCH1 and SMO expression. Protein expression was assessed through immunohistochemistry. Clinicopathological parameters were correlated with gene and protein expression. Statistical analysis included Pearson chi-square tests, co-relation co-efficient tests, Kaplan-Meier survival analysis and ROC curve analysis. PTCH1 expression correlated with lymphatic permeation (p = 0.002) and tumor stage (p = 0.002), while SMO expression correlated with lymph node status (p = 0.034) and tumor stage (p = 0.021). PTCH1 gene expression correlated with lymph node status (p = 0.024). High PTCH1 gene expression was associated with shorter survival in tongue cancer patients. ROC curve analysis indicated diagnostic potential for PTCH1 and SMO gene and cytoplasmic SMO expression in distinguishing malignant tissues from adjacent normal tissues. PTCH1 and SMO play a crucial role in oral cancer progression, correlating with tumor stages and metastatic potential. Despite not directly influencing overall survival, PTCH1 expression at specific anatomical sites hints at its prognostic implications. PTCH1 and SMO exhibit diagnostic potential, suggesting their utility as molecular markers in oral cancer management and therapeutic strategies.

Expression of Forkhead Box M1 and Anticancer Effects of FOXM1 Inhibition in Epithelioid Sarcoma

Epithelioid sarcoma (ES) is a rare aggressive sarcoma that, unlike most soft-tissue sarcomas, shows a tendency toward local recurrence and lymph node metastasis. Novel antitumor agents are needed for ES patients. Forkhead box transcription factor 1 (FOXM1) is a member of the Forkhead transcription factor family and is associated with multiple oncogenic functions; FOXM1 is known to be overexpressed and correlated with pathogenesis in various malignancies. In this study, we immunohistochemically analyzed FOXM1 expression levels and their clinical, clinicopathologic, and prognostic significance in 38 ES specimens. In addition, to investigate potential correlations between FOXM1 downregulation and oncologic characteristics, we treated ES cell lines with thiostrepton, a naturally occurring antibiotic that inhibits both small interfering RNA (siRNA) and FOXM1. In the analyses using ES samples, all 38 specimens were diagnosed as positive for FOXM1 by immunohistochemistry. We separated specimens into high (n = 19) and low (n = 19) FOXM1–protein expression groups by staining index score, and into large (n = 12), small (n = 25), and unknown (n = 1) tumor-size groups using a cutoff of 5 cm maximum diameter. Although there were significantly more samples with high FOXM1 expression in the large tumor group (P = .013), there were no significant differences with respect to age (P = 1.00), sex (P = .51), primary site of origin (P = .74), histologic subtypes (P = 1.00), depth (P = .74), or survival rate (P = .288) between the high and low FOXM1–protein expression groups. In the in vitro experiments using ES cell lines, FOXM1 siRNA and thiostrepton successfully downregulated FOXM1 mRNA and protein expression. Furthermore, downregulation of FOXM1 inhibited cell proliferation, drug resistance against chemotherapeutic agents, migration, and invasion and caused cell cycle arrest in the ES cell lines. Finally, cDNA microarray analysis data showed that FOXM1 regulated cIAP2, which is one of the apoptosis inhibitors activated by the TNFα-mediated NF-κB pathway. In conclusion, the FOXM1 gene may be a promising therapeutic target for ES.

Analysis of risk factors and construction of nomogram model for local lymph node metastasis in salivary gland mucoepidermoid carcinoma

Objective: To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC. Methods: The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software. Results: Multivariate logistic regression results showed that M stage [OR(95%CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[OR(95%CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [OR(95%CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion: M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

Retroperitoneal leiomyosarcoma; Demographics, clinicopathological, survival analysis, role of adjuvant radiation and genomic analysis.

e23327 Background: Retroperitoneal leiomyosarcoma (RPL) is an exceedingly rare malignancy and is the second most common subtype of leiomyosarcomas. Most of the information concerning this rare disease is limited to case studies and few literature studies. The study's objectives were to assess the demographics, pathological factors, survival outcomes, genomic landscape and potential for targeted therapy. Methods: Data of retroperitoneal leiomyosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, with cases diagnosed between 2000 and 2020 used for this study and the Cancer Genome Atlas containing sequencing information for 27 cases of RPL. Results: A total of 1406 cases were extracted with mean age of diagnosis of 62.1 years. Of these, RPL had a higher incidence in women (71.5%), more cases affected Whites (58.7%). Histologically, in patients with known grading, most patients’ i.e. 62.35% were grade 3, G3 (poorly differentiated). Nearly all (99.9%) patients presented with a tumor size ≥4.1 cm. Local lymph nodes metastasis were positive in 76.0% of cases when lymph node status was reported. In known cases of distant metastases, the most common site was liver (8.9%). The main treatment modality was surgery only (26.7%, hazard ratio, HR 1.17, p-value &lt; 0.001), followed by the standard of care (surgery and radiation) (18.4%, HR 1.03, p-value &lt; 0.001), and radiation only (18.4%). Five-year overall survival was 40% and 5-year cause-specific survival was 64%. The highest 5-year survival was observed in patients undergoing surgery and radiation (57%), and in combination therapy (chemotherapy, surgery, and radiation) the 5-year survival was 39%. Genetic analysis found the most common mutations included TP53 (51.9%), RB1 (25.9%), and ATRX (14.8%). When accounting for deep deletions and rearrangements, total frequency of the alterations was higher such that TP53 (63.0%), RB1 (51.9%), and ATRX (18.5%). Potentially actionable alterations were rare but included activating alterations in FGFR1, PIK3CA and ESR1, as well as deep deletions of BRCA1. Conclusions: Retroperitoneal leiomyosarcoma is a very rare tumor where surgery and radiation has been the conventional therapy. Our study indicates there are genetic alterations in the majority of retroperitoneal leiomyosarcoma. To further understand the pathogenesis and survival factors, patients with RPL should be enrolled into national and international registries.

4-nitroquinoline 1-oxide-induced oral epithelial lesions exhibit time- and stage-dependent changes in the tumor immune microenvironment.

Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity and is associated with high morbidity due to local invasion and lymph node metastasis. Tumor infiltrating lymphocytes (TILs) are associated with good prognosis in oral cancer patients and dictate response to treatment. Ectopic sites for immune activation in tumors, known as tertiary lymphoid structures (TLS), and tumor-associated high-endothelial venules (TA-HEVs), which are specialized lymphocyte recruiting vessels, are associated with a favorable prognosis in OSCC. Why only some tumors support the development of TLS and HEVs is poorly understood. In the current study we explored the infiltration of lymphocyte subsets and the development of TLS and HEVs in oral epithelial lesions using the 4-nitroquinoline 1-oxide (4NQO)-induced mouse model of oral carcinogenesis. We found that the immune response to 4NQO-induced oral epithelial lesions was dominated by T cell subsets. The number of T cells (CD4+, FoxP3+, and CD8+), B cells (B220+) and PNAd+ HEVs increased from the earliest to the latest endpoints. All the immune markers increased with the severity of the dysplasia, while the number of HEVs and B cells further increased in SCCs. HEVs were present already in early-stage lesions, while TLS did not develop at any timepoint. This suggests that the 4NQO model is applicable to study the dynamics of the tumor immune microenvironment at early phases of oral cancer development, including the regulation of TA-HEVs in OTSCC.

Salivary carcinoma showing thymus-like differentiation: clinicopathological analysis of 7 cases

Objective: To analyze the clinicopathological features of salivary carcinoma showing thymus-like differentiation(CASTLE). Methods: Cases diagnosed with salivary CASTLE from January 2020 to December 2023 were collected and selected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. A total of 7 cases of salivary CASTLE were identified. All the cases originated from parotid. There were 3 males and 4 females. The patients' age range was 11-70 years.The clinical, microscopic, immunohistochemical and prognostic features of these cases were analyzed. Results: The duration of disease ranged from 1 month to 1 year, and 1 patient had facial numbness and 1 with swelling sensation occasionally. Radiographically, 4 cases showed malignant signs. Microscopically, 4 cases involved in parotid gland, and all the tumors had different degrees of lymphoid tissue background. The tumor cells arranged in nests, 5 cases with lymphoepithelial carcinoma-like and 2 cases with squamous cell carcinoma morphology. The tumor cells expressed CD5 and CD117 proteins diffusely in lymphoepithelial carcinoma-like cases. However, the tumor cells expressed CD5 diffusely and CD117 focally in cases with squamous cell carcinoma morphology. All the cases had no Epstein-Barr virus infection. Among the 6 patients with follow-up information, all of them underwent postoperative radiotherapy, and none of them had local recurrence and lymph node metastasis. Conclusions: Salivary CASTLE is a rare tumor, it should be distinguished from lymphoepithelial carcinoma and squamous cell carcinoma. The patients often have better prognosis and CD5 protein expression has a valuable role in the differential diagnosis.

Transoral robotic thyroidectomy via vestibular approach: a retrospective study of 107 cases in a single center

Objective: To investigate the short-term outcome of transoral robotic thyroidectomy. Methods: This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960th Hospital of People's Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results: All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized (M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection (n=1), left submandibular perforation (n=1), skin scald (n=1), and perioral numbness (n=1), oral tear (n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion: For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2–1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

Abstract 6801: Cellular senescence involves spatial evolution in colorectal cancer

Abstract Cancer evolution is a continuous process involving cellular changes that promote progression and metastasis. Recent studies demonstrate that cancer evolution is spatially associated: a phenomenon called “the spatial evolution of cancer.” In our data, colorectal cancer cells gradually evolve from an adenoid to a collective invasion morphology, ultimately developing a partial epithelial-mesenchymal transition phenotype as they form an invasive front. Trajectory analysis showed that cancer cells at the invasive front of a tumor exhibit a totally different gene expression pattern from those at the center, and that cellular senescence plays a crucial role in this transition. Epigenetic changes in the promoter/exon1 region of the CDKN2A gene caused by increased reactive oxygen species level are crucial for expression of p16INK4A and induction of senescence in the cancer cells. Two types of senescent tumor cells (type I and type II) were observed, and they played different roles in cancer progression due to different gene expression. Type II senescent tumor cells (p16INK4A+/LAMC2+/MMP7+), a final evolved form of cancer cells, are strongly associated with local invasion and lymph node metastasis of colorectal cancer and worsen the prognosis for patients. Citation Format: Tae Jun Park, Seok Yun Kang, Jang Hee Kim, Hyun Woo Lee, Yong Won Choi, Soon Sang Park, Young-Kyoung Lee. Cellular senescence involves spatial evolution in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6801.

Head-to-head comparison of prostate-specific membrane antigen positron emission tomography/computed tomography and multiparametric magnetic resonance imaging in the detection of biochemical recurrence of prostate cancer: a systematic review and meta-analysis

Our main goal of this meta-analytical analysis was to evaluate the diagnostic effectiveness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) against multiparametric magnetic resonance imaging (mpMRI) in the context of identifying biochemical recurrence in patients with prostate cancer (PCa). A thorough search covering articles published until March 2023 was carried out across major databases such as PubMed, Embase, and Web of Science. Studies examining the direct comparison of PSMA PET/CT and mpMRI in patients with PCa suffering biochemical recurrence were included in the inclusion criteria. Using the renowned Quality Assessment of Diagnostic Performance Studies-2 technique, each study's methodological rigor was assessed. We analyzed data from six eligible studies involving 290 patients in total. The combined data showed that for PSMA PET/CT and mpMRI, respectively, the pooled overall detection rates for recurrent PCa after definitive treatment were 0.69 (95% confidence interval [CI]: 0.45-0.89) and 0.70 (95% CI: 0.44-0.91). The detection rates for local recurrence were specifically 0.52 (95% CI: 0.39-0.65) and 0.62 (95% CI: 0.31-0.89), while they were 0.50 (95% CI: 0.26-0.74) and 0.32 (95% CI: 0.18-0.48) for lymph node metastasis. Notably, there was no discernible difference between the two imaging modalities in terms of the overall detection rate (P = 0.95). The detection rates for local recurrence and lymph node metastasis did not differ statistically significantly (P = 0.55, 0.23). The performance of PSMA PET/CT and mpMRI in identifying biochemical recurrence in PCa appears to be comparable. However, the meta-analysis' findings came from research with modest sample sizes. In this context, more extensive research should be conducted in the future.