Metastasis Of Squamous Cell Carcinoma Research Articles

A case controlled study of risk factors for metastatic squamous cell carcinoma in organ transplant recipients: single academic medical center.

Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

Nodal Metastasis in Oral Squamous Cell Carcinoma: an Analysis of Risk Factors and Influence on Overall Survival

Introduction: Oral squamous cell carcinoma (OSCC) presents a high tendency of lymph node metastasis (LNM). Objective: Determine which risk factors play a significant role in metastasis to cervical lymph nodes and to evaluate the influence of nodal involvement on overall survival of patients with OSCC. Method: Medical records of 350 patients with OSCC were retrospectively reviewed. The data were analyzed using the chi-square, Fisher’s exact and log-rank Mantel Cox tests and multinomial and Cox logistic regression. Results: Of the 350 medical records evaluated, 251 reported N0, 75 N1, 16 N2 and 8 N3. Male gender, referrals from private health care providers, T3/4 stage and non-surgical treatments were associated with LNM. In multivariate analysis, men and T3/4 tumors were shown to be independent risk factors for LNM. The independent risk factors for survival were male gender, nodal involvement (p = 0.017) and non-surgical treatment. Conclusion: Male gender and T-stage are risk factors for LNM in patients with OSCC. Moreover, the presence of LNM and age >65 years are associated with poor overall survival.urvivor.

Long non-coding RNA MAGEA4-AS1 binding to p53 enhances MK2 signaling pathway and promotes the proliferation and metastasis of oral squamous cell carcinoma

Long non-coding RNAs (lncRNAs) regulate the occurrence, development and progression of oral squamous cell carcinoma (OSCC). We elucidated the expression features of MAGEA4-AS1 in patients with OSCC and its activity as an OSCC biomarker. Furthermore, the impact of up-regulation of MAGEA4-AS1 on the cellular behaviors (proliferation, migration and invasion) of OSCC cells and intrinsic signal mechanisms were evaluated. Firstly, we analyzed MAGEA4-AS1 expression data in The Cancer Genome Atlas (TCGA) OSCC using a bioinformatics approach and in 45 pairs of OSCC tissues using qPCR. Then CCK-8, ethynyl deoxyuridine, colony formation, transwell and wound healing assays were conducted to assess changes in the cell proliferation, migration and invasion protential of shMAGEA4-AS1 HSC3 and CAL27 cells. The RNA sequence of MAGEA4-AS1 was identified using the rapid amplification of cDNA ends (RACE) assay. And whole-transcriptome sequencing was used to identify MAGEA4-AS1 affected genes. Additionally, dual-luciferase reporter system, RNA-binding protein immunoprecipitation (RIP), and rescue experiments were performed to clarify the role of the MAGEA4-AS1-p53-MK2 signaling pathway. As results, we found MAGEA4-AS1 was up-regulated in OSCC tissues. We identified a 418 nucleotides length of the MAGEA4-AS1 transcript and it primarily located in the cell nucleus. MAGEA4-AS1 stable knockdown weakened the proliferation, migration and invasion abilities of OSCC cells. Mechanistically, p53 protein was capable to activate MK2 gene transcription. RIP assay revealed an interaction between p53 and MAGEA4-AS1. MK2 up-regulation in MAGEA4-AS1 down-regulated OSCC cells restored MK2 and epithelial-to-mesenchymal transition related proteins’ expression levels. In conclusion, MAGEA4-AS1-p53 complexes bind to MK2 promoter, enhancing the transcription of MK2 and activating the downstream signaling pathways, consequently promoting the proliferation and metastasis of OSCC cells. MAGEA4-AS1 may serve as a diagnostic marker and therapeutic target for OSCC patients.

Risk factors and impact of occult and skip metastasis in early-stage oral tongue squamous cell carcinoma.

To investigate risk factors associated with occult lymph node metastases (ONM) and skip metastasis in early-stage oral tongue squamous cell carcinoma (OTSCC) patients. Meanwhile, to analyze the contribution of metastatic nodes to survival outcomes. 544 OTSCC patients who were clinically staged T1-T2N0 with pathologic results from May 2018 to January 2024 were enrolled. Those with ONM were divided into subgroups with or without skip metastasis. Clinical, laboratorial, radiological and pathological factors between groups were analyzed by using univariate analysis and multivariate logistic analysis. The association of tumor growth behavior with the metastatic pattern of lymph nodes was summarized. Additionally, disease free survival (DFS) among different groups were compared using Kaplan-Meier analysis. Tumor growth behavior was associated with ONM. Tumor thickness with a threshold of 6.4mm was not inferior to histological depth of invasion in predicting ONM. Only 1.3% of patients had nodal involvement of neck level IV or V. The DFS of patients with ONM were significantly reduced than those without ONM (P<0.001). The DFS between patients with and without skip metastasis exhibited no statistical significance(P = 0.246). The 1-year, 2-year recurrence rates of patients with or without ONM were 31.9%, 37.5%, 10.1% and 14.0%, correspondingly. Tumor thickness with a threshold of 6.4mm could be used as a preoperative predictor for ONM. Elective neck dissection of level I - III might be sufficient for early stage OTSCC patients. OTSCC patients with ONM should be closely observed during the first 2 years after surgery. The risk of ONM in early stage OTSCC patients might be predicted by tumor thickness calculated on MR imaging. Elective neck dissection of level I - III could remove micrometastases timely and effectively.

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery

Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery. A total of 101 patients with OSCC resection and cervical lymph node dissection were identified. p53 immunohistochemistry was performed for all cases and scored into p53 wild-type (p53-HPV: midepithelial/basal sparing, markedly reduced [null-like]/basal sparing; p53-conventional: scattered basal, patchy basal/parabasal) and p53-abnormal (overexpression basal/parabasal only, overexpression basal/parabasal to diffuse, null, and cytoplasmic) patterns. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization were used to confirm the HPV status in cases showing midepithelial/basal sparing or markedly reduced (null-like)/basal sparing pattern. Logistic regression analysis was performed to investigate the association of p53 status, tumor size, depth of invasion, and pT stage against lymph node status. We identified 22 cases with p53 wild-type patterns (16 p53-conventional, 6 p53-HPV) and 79 cases with p53-abnormal patterns. Two of 22 p53 wild-type cases had positive lymph nodes (1 p53-conventional, 1 p53-HPV), whereas 40 of 79 p53-abnormal cases had positive lymph nodes (P < .001). Multivariate analysis showed that p53-abnormal pattern was an independent risk factor associated with positive node(s) with an odds ratio of 8.12 (95% CI, 2.10-53.78; P = .008).p53-Abnormal OSCCs were significantly more likely to be associated with positive lymph node status than p53 wild-type OSCCs at the time of surgery. Further investigation with long-term follow-up is required to determine its clinical application before surgery planning.

PREVALENCE OF OCCULT CERVICAL LYMPH NODES METASTASIS IN CN0 IN ORAL SQUAMOUS CELL CARCINOMA (OSCC)

Occult metastasis is not easily detected clinically or radiographically. Various methods have been applied for neck control for clinically N0 via elective neck dissection (END), wait and watch (W&W) and sentinel lymph node biopsy (SLNB). The main aim of this study is to investigate the prevalence of occult cervical lymph nodes metastasis in cN0 in oral squamous cell carcinoma, to investigate and compare the disease-free state and overall survival rate between occult metastasis and the non-occult group that presented at the oral and maxillofacial surgery clinic, Faculty of Dentistry, Universiti Malaya. This is a retrospective study involving 48 patients with complete data from 2008 to 2019. Data collected includes socio-demographic and clinicopathologic factors. Descriptive analysis was performed and Kaplan-Meier analysis was used to compare disease-free status and overall survival period between occult and non-occult metastases groups. The prevalence of occult metastasis in oral squamous cell carcinoma (OSCC) was low at 8.3% but it became 100% on OSCC tongue. The main tumor site for occult metastasis originated from the oral tongue with T2 size. Non-occult group had better overall survival rate comparing to occult metastasis group and the advanced group. Therefore, END is recommended particularly for N0 OSCC tongue.

Tumor budding and complete epithelial mesenchymal transition correlate with late nodal metastasis in early-stage tongue squamous cell carcinoma

BackgroundLate nodal metastasis is a poor prognostic factor for early-stage tongue squamous cell carcinoma. However, for most early-stage patients, there is a low risk for late nodal metastasis, which currently lacks a diagnostic marker. Tumor budding is a nodal metastasis risk factor in other human cancers. Here, we evaluated tumor budding by partial or complete epithelial-mesenchymal transition and Ovol2 expression, a transcription factor that directly suppresses epithelial-mesenchymal transition. MethodsSixty-six T1–2N0 patients were enrolled in this retrospective study. Tumor expressions of E-cadherin and vimentin (epithelial-mesenchymal transition markers) and Ovol2 were assessed by immunohistochemistry. Tumor histopathological and immunohistochemical features, mode of invasion, and tumor budding were assessed. Correlations between these potential predictive factors and late nodal metastasis were determined statistically. ResultsUnivariate analysis demonstrated lymphoid infiltrate, perineural invasion, infiltrative growth pattern, tumor budding, vimentin positive, and complete epithelial-mesenchymal transition were significant factors of late nodal metastasis (all P < 0.05), observed in 25.8 % of patients. Multivariate analysis identified tumor budding and vimentin positive were independent prognostic factors (both P < 0.025). Ovol2 expression was significantly decreased in partial and complete epithelial-mesenchymal transition cells (both P < 0.01) compared with normal epithelia. Univariate analysis, but not multivariate analysis, showed Ovol2 correlated with depth of invasion and tumor budding (both P < 0.05). ConclusionTumor budding and vimentin expression are risk factors for late nodal metastasis in T1–2N0 tongue squamous cell carcinoma. Ovol2 might be involved in the early stages of epithelial-mesenchymal transition. Evaluation of these factors might identify patients susceptible to late nodal metastasis who require elective neck dissection.

Clinicopathological Factors Associated with Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma: A Retrospective Analysis

Abstract Background: Metastasis to regional cervical lymph nodes is an important prognostic factor for oral-cavity squamous cell carcinomas (OSCC). However, it is difficult to predict nodal metastasis in OSCC. The current study was done with an aim to find the association of various clinicopathological factors to the presence of cervical lymph node metastasis in OSCC. Materials and Methods: A retrospective analysis of hospital records from January 2020 to June 2023 was conducted in a tertiary care center. The records of 65 patients were included as per the inclusion criteria. The data were divided into two groups based on the presence or absence of neck nodal metastasis. Various factors such as tumor size, volume, depth of invasion (DOI), lymphovascular invasion, and perineural invasion were statistically compared between the study groups. Results: The oral tongue was the most common subsite (25, 38.5%), followed by buccal mucosa (18, 27.7%). The mean DOI in the group with cervical lymph node metastasis was 9.83 ± 4.83 mm, and it was significantly higher than the group without cervical lymph node metastasis (6.15 ± 4.20 mm, P = 0.004). Conclusion: DOI assessment is one of the most important preoperative assessments in the clinicoradiological assessment of OSCC cases. Further, it is recommended that in cases with DOI &gt;5 mm, the intraoperative frozen section on the nodes dissected in elective neck dissection is done for further determination of the extent of neck dissection.

ROS-mediated ITGB5 promotes tongue squamous cell carcinoma metastasis through epithelial mesenchymal transition and cell adhesion signal pathway

PurposeIntegrin β5 (ITGB5) is an integrin β subunit member widely expressed in the human bodies, especially in cancer cells and tissues, which is a key factor in promoting tumor metastasis. In this study we investigated the differential expression of ITGB5 in tongue squamous cell carcinoma (TSCC), especially in those with lymph node metastasis, and revealed the possible mechanism.MethodsThe expression of ITGB5 in TSCC was analyzed by database and verified by immunohistochemistry through 135 TSCC patients’ tissue sections from Sun Yat-sen Memorial Hospital and Guangzhou First People’s Hospital. The relationship between ITGB5 and lymph node metastasis or prognosis was analyzed retrospectively. The effects of ITGB5 on TSCC cells were examined through knocking down or overexpression and its possible regulator and signal pathway were explored.ResultsThe expression of ITGB5 in TSCC was higher than that in adjacent tissue, and the expression in patients with lymph node metastasis was higher than that in patients without lymph node metastasis. The high expression of ITGB5 predicted a worse prognosis. Knock down of ITGB5 suppressed invasion and migration of TSCC cells, while overexpression of ITGB5 contributed to invasion and migration. Reactive oxygen species (ROS) regulated epithelial mesenchymal transition (EMT), and we further verified that ROS enhanced the expression of ITGB5 to promote the metastasis of TSCC. Mechanistically, ITGB5 functions through cell adhesion signal pathway.ConclusionThe increased expression of ITGB5 in tongue squamous cell carcinoma with lymph node metastasis may be a potential target for evaluating lymph node metastasis and worse prognosis of tongue squamous cell carcinoma. Scavenge of ROS or knock down of ITGB5 may be the strategies to overcome metastasis of TSCC.

Metastatic malignancies in the parotid gland: A retrospective study

The aim of this study was to compare treatment modalities, pathological and clinical characteristics, and outcomes in patients with metastasis in a parotid gland.The medical records of 34 patients who received treatment for metastasis in the parotid gland over a twenty-year period were evaluated. Patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) metastasis were retrospectively reclassified using the P/N and N1S3 staging system.Patients with neck metastasis showed a significantly poorer prognosis (P = 0.025). Univariate analysis also revealed that extent of parotidectomy and type of neck dissection did not influence recurrence free survival (RFS) and overall survival (OS). When comparing the usefulness of the P/N and S1N3 staging systems, a positive correlation was observed between the P stage and the N1S3 stage in both RFS and OS.The extent of parotidectomy and concomitant neck dissection is still under discussion. Total parotidectomy and modified radical neck dissection did not improve RFS and OS. N1S3 is a less complex classification and possesses a higher predictive value when compared to the P/N staging system.

Esophagectomy in patients with esophageal squamous cell carcinoma and distant nodal metastasis.

The role of surgery in oligometastatic esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the oncological outcomes after esophagectomy in patients with ESCC with distant lymph node (LN) metastasis. Patients with ESCC and nodal metastasis treated with chemoradiotherapy or chemotherapy followed by esophagectomy between 2010 and 2020 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients with distant LN metastasis (dLN+) and exclusively regional LN metastasis (dLN-). The cohort comprised 69 dLN+ and 111 dLN- patients. Survival was significantly better in the dLN- group than in the dLN+ group (5-year OS, 51.9% vs. 25.5%, P < 0.001; RFS, 47.2% vs. 18.1%, P < 0.001). Stratified by the yp stage, 49 (44.1%) dLN- and 30 (43.5%) dLN+ patients achieved a pathological complete response (pCR). In the dLN- and dLN+ groups, the OS rates were significantly higher in the pCR group than in the non-pCR group (dLN-: 76.7% vs. 32.4%, P < 0.001; dLN+: 39.6% vs. 14.2%; P = 0.002). The dLN-/pCR group had the best OS, significantly outperforming the dLN-/non-pCR and dLN+/pCR groups. OS did not differ between the dLN-/non-pCR and dLN+/pCR groups. The dLN+/non-pCR group had the worst OS. The RFS analysis paralleled the OS findings. Patients with dLN+ disease had worse outcomes than their dLN- counterparts, irrespective of the pCR status. The survival rates were poor but comparable between the dLN+/pCR and dLN-/non-pCR groups. Adjuvant therapy may be required for dLN+ patients following systemic treatment and surgery, even after achieving pCR.

A Splice Form of VEGF, a Potential Anti-Angiogenetic Form of Head and Neck Squamous Cell Cancer Inhibition.

Angiogenesis, primarily mediated by vascular endothelial growth factor (VEGF), is a fundamental step in the progression and metastasis of head and neck squamous cell carcinoma (HNSCC). Traditional anti-angiogenic therapies that target the VEGF pathway have shown promise but are often associated with significant side effects and variable efficacy due to the complexity of the angiogenic signaling pathway. This review highlights the potential of a specific VEGF splice form, VEGF165b, as an innovative therapeutic target for HNSCC. VEGF165b, unlike standard VEGF, is a natural inhibitor that binds to VEGF receptors without triggering pro-angiogenic signaling. Its distinct molecular structure and behavior suggest ways to modulate angiogenesis. This concept is particularly relevant when studying HNSCC, as introducing VEGF165b's anti-angiogenic properties offers a novel approach to understanding and potentially influencing the disease's dynamics. The review synthesizes experimental evidence suggesting the efficacy of VEGF165b in inhibiting tumor-induced angiogenesis and provides insight into a novel therapeutic strategy that could better manage HNSCC by selectively targeting aberrant vascular growth. This approach not only provides a potential pathway for more targeted and effective treatment options but also opens the door to a new paradigm in anti-angiogenic therapy with the possibility of reduced systemic toxicity. Our investigation is reshaping the future of HNSCC treatment by setting the stage for future research on VEGF splice variants as a tool for personalized medicine.

LNMAC Promotes Cervical Squamous Cell Carcinoma Lymphatic Metastasis via Epigenetic Regulation of FGF2-Induced Lymphangiogenesis.

The lymph node is the most common site of distant metastasis of cervical squamous cell carcinoma (CSCC), which elicits dismal prognosis and limited efficiency for treatment. Elucidation of the mechanisms underlying CSCC lymphatic metastasis would provide potential therapeutic strategies for nodal metastatic of CSCC. Here, based on in vivo lymphatic metastasis screening model, a circular RNA is identified that is termed as lymph node metastasis associated circRNA (LNMAC), is markedly upregulated in lymphatic metastatic CSCC and correlated with lymph node metastasis. Overexpression of LNMAC dramatically augments the metastatic capability of CSCC cells to the lymph node via inducing lymphangiogenesis. Mechanistically, LNMAC epigenetically upregulates fibroblast growth factor 2 (FGF2) expression by directly associating with histone acacetylase 1 (HDAC1), preventing Importin α6/8-mediated nuclear translocation of HDAC1 and eliciting histone H3K27ac-induced FGF2 transcriptional activation. Treatment with 3F12E7, an anti-FGF2 monoclonal antibody, effectively inhibits LNMAC-induced CSCC lymphatic metastasis. Taken together, these findings indicate that LNMAC plays a crucial role in FGF2-mediated lymphangiogenesis and lymphatic metastasis, highlighting that LNMAC might be a therapeutic target for lymph node metastasis in CSCC patients.

DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma.

Tumor invasion and metastasis are the underlying causes of high mortality rate due to oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for an in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ-associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA sequencing analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation to accumulate in the nucleus where it enhanced cytochrome c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In samples from patients with OSCC, expression of DAZAP1 positively correlated with COX16 and a high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis. Significance: The RNA-binding protein DAZAP1 undergoes phase separation to enhance COX16 expression and mediate metabolic reprogramming that enables tumor metastasis, highlighting DAZAP1 as a potential metabolic target for cancer therapy.

A Systematic Review of Occult Contralateral Neck Metastasis in Tonsillar Squamous Cell Carcinoma.

To determine the prevalence of occult contralateral nodal metastasis in tonsillar squamous cell carcinoma (TSCC) in patients who have undergone bilateral neck dissection. A systematic review of English articles identified from PubMed, Embase, and Web of Science databases. Search terms included "oropharynx," "carcinoma," "lymph node," and "neck dissection." Two reviewers independently screened abstracts, reviewed full texts, and extracted data from all studies that presented the prevalence of contralateral occult nodal metastasis in TSCC. The overall prevalence of occult contralateral nodal metastasis was 10%. The prevalence was 8% for cT1/T2 tumors, 19% for cT3/T4, 1% for N0 in the ipsilateral neck, and 12% for N+. Occult contralateral lymph nodes were most frequently found in neck level II (81%) and level III (19%). No metastatic nodes were found in level I. Elective neck dissection of the contralateral neck in TSCC is controversial due the historic morbidity caused by the surgery. A widely accepted recommendation suggests performing an elective neck dissection when the prevalence of occult metastasis is between 15% and 20%. The results of this study suggest that elective contralateral neck dissection will identify occult positivity in 19% of patients with T3/T4 tonsil cancer. In T1/T2 or N0 tumors, the diagnostic yield would be considerably lower at 8% and 1%, respectively. Contralateral nodal sampling could be considered based on patient preference after adequate counseling on the risks/benefits of occult nodal detection. More research is needed on other nodal features to formulate treatment guidelines. Laryngoscope, 2024.

Effectiveness of microsurgical palatal tonsillectomy in patients with oropharyngeal cancer and metastases of squamous cell carcinoma into the cervical lymph nodes without identified primary lesion

Introduction. Metastasis without an identified primary lesion is an unresolved and complex problem in clinical oncology. The issue of the necessity of primary lesion identification remains controversial. According to some studies, detection of the primary tumor potentially reduces the dose of radiation therapy and therefore prevents development of toxic reactions that reduce the quality of life of the patient, and in some cases completely eliminates the need for adjuvant therapy. Widespread development and application of robotic, microsurgical, and laser transoral techniques make it possible to verify latent oropharyngeal cancer. The detection of overexpression of p16 protein in metastatic affected lymph nodes may indicate the association of this pathology with human papillomavirus.Aim. To investigate the efficacy of microsurgical palatal tonsillectomy (using a surgical microscope) in diagnosis and treatment of occult oropharyngeal cancer in patients with cervical lymph node metastases of undetected primary site, determine the frequency of expression of the surrogate marker of human papillomavirus – protein p16.Materials and methods. The study was based on the results of diagnosing 82 patients with cervical lymph node metastases of undetected primary site. The inclusion criteria were morphologically verified cervical lymph node metastases of squamous cell carcinoma, absence of a primary tumour after a standard clinical examination. 10 patients underwent palatal tonsillectomy using a surgical microscope and cervical lymph node dissection based on the results of clinical examination and instrumental diagnostics.Results. The use of microsurgical palatal tonsillectomy in patients with metastases of squamous cell carcinoma in the cervical lymph nodes without identified primary lesion allowed to diagnose cancer of the palatine tonsil in 12.1 % of cases, cancer of this location associated with human papilloma virus in 70 % of cases.Conclusion. Microsurgical palatal tonsillectomy using a surgical microscope allowed us to not only verify occult palatine tonsil cancer, but also to establish accurate diagnosis and stage of the disease with subsequent determination of the scope of adjuvant therapy.

Single-cell atlas profiling revealed cellular characteristics and dynamic changes after PD-1 blockade therapy of brain metastases from laryngeal squamous cell carcinoma.

Brain metastasis (BM) in laryngeal squamous cell carcinoma (LSCC) is uncommon but prognosis is poor. Anti-PD-1 immunotherapy benefits some advanced LSCC cases, yet its efficiency is limited by tumor complexity. We analyzed paired metastatic tumor samples from before and after immunotherapy using single-cell RNA sequencing (scRNA-seq), along with a primary LSCC dataset and bulk RNA sequencing. This identified changes post-immunotherapy and revealed differences in single-cell transcriptomes among LSCC, primBM, and neoBM. Our findings show that anti-PD-1 treatment suppresses metastasis-promoting pathways like VEGF and EMT in cancer cells, and alters immune cell functions. Notably, it upregulates T cell activation, leading to CD8 T cell exhaustion from excess heat shock proteins, notably HSPA8. However, CD8 T cell cytotoxic functions improve post-treatment. In myeloid cells, anti-PD-1 therapy enhances antigen presentation and promotes a proinflammatory shift post-metastasis. Additionally, NUPR1 is linked to BM in LSCC, and NEAT1 is a potential metastatic cancer cell cycle participant. Our study provides insights into cancer heterogeneity and the impact of PD-1 immunotherapy on metastasis, aiding precise diagnosis and prognosis.

Risk of lymph node metastasis in T1 tonsil squamous cell carcinomas patients according to age stratification at diagnosis

BackgroundThe objective of this study is to assess the association between age and lymph nodes metastasis (LNM) in T1 tonsil squamous cell carcinomas (TSCC) patients. MethodsPatients with T1 TSCC were extracted from the SEER database between 2005 and 2014. Univariate and multivariate logistic regression models were produced to recognize the association between age and risk factors of LNM. ResultsA total of 2430 patients were analyzed. Younger patients more frequently presented with LNM compared to their older peers (P < 0.01, respectively.). In multivariate analyses, older age was associated with a significantly lower risk of LNM. Compared to patients aged 29–39-years-old, the hazard ratios for patients aged 40–49, 50–59, 60–69, and 70–88 years old were 0.911 (95 % confidence interval [CI] 0.370–2.245), 0.641 (95 % CI 0.268–1.535), 0.511 (95 % CI 0.212–1.231), and 0.236 (95 % CI 0.095–0.584), respectively. Subgroups analysis shows that the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients (P < 0.05, respectively). ConclusionOur study demonstrates that younger patients with T1 TSCC had a higher risk of LNM than their old peers and the effect of older age was significantly associated with a lower risk of LNM in all groups except for Asian patients. More accurate assessments of LNM and prophylactic neck dissection or prophylactic adjuvant radiation therapy to neck will be imperative for reducing recurrence in younger T1 TSCC.

Dual-energy computed tomography for predicting cervical lymph node metastasis in laryngeal squamous cell carcinoma

Rationale and objectivesWe constructed a dual-energy computed tomography (DECT)-based model to assess cervical lymph node metastasis (LNM) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methodsWe retrospectively analysed 164 patients with LSCC who underwent preoperative DECT from May 2019 to May 2023. The patients were randomly divided into training (n = 115) and validation (n = 49) cohorts. Quantitative DECT parameters of the primary tumours and their clinical characteristics were collected. A logistic regression model was used to determine independent predictors of LNM, and a nomogram was constructed along with a corresponding online model. Model performance was assessed using the area under the curve (AUC) and the calibration curve, and the clinical value was evaluated using decision curve analysis (DCA). ResultsIn total, 64/164 (39.0 %) patients with LSCC had cervical LNM. Independent predictors of LNM included normalized iodine concentration in the arterial phase (odds ratio [OR]: 8.332, 95 % confidence interval [CI]: 2.813–24.678, P < 0.001), normalized effective atomic number in the arterial phase (OR: 5.518, 95 % CI: 1.095–27.818, P = 0.002), clinical T3-4 stage (OR: 5.684, 95 % CI: 1.701–18.989, P = 0.005), and poor histological grade (OR: 5.011, 95 % CI: 1.003–25.026, P = 0.049). These predictors were incorporated into the DECT-based nomogram and the corresponding online model, showing good calibration and favourable performance (training AUC: 0.910, validation AUC: 0.918). The DCA indicated a significant clinical benefit of the nomogram for estimating LNM. ConclusionsDECT parameters may be useful independent predictors of LNM in patients with LSCC, and a DECT-based nomogram may be helpful in clinical decision-making.

Fucoxanthin Inhibits the Proliferation and Metastasis of Human Pharyngeal Squamous Cell Carcinoma by Regulating the PI3K/Akt/mTOR Signaling Pathway.

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.