Invasive Squamous Cell Carcinoma Research Articles

Subtraction CT Improves Detectability of Mandibular Bone Invasion in Oral Squamous Cell Carcinoma.

Pretreatment evaluation of bone invasion in head and neck cancer is critical for treatment strategies. We investigated the usefulness of subtraction CT (SCT) in evaluating mandibular bone invasion in oral squamous cell carcinoma (OSCC). This retrospective investigation included patients with OSCC who underwent surgery at the Shizuoka Cancer Center Hospital between 2018 and 2022. We evaluated tumor invasion of the mandibular bone by interpreting conventional computed tomography (CT), SCT, and magnetic resonance imaging (MRI) and comparing the findings with the pathological examination. Sensitivity and specificity were compared using the McNemar test, whereas Spearman's correlation and Bland-Altman methods were utilized to assess mandibular bone invasion depth. A total of 71 patients were enrolled. SCT showed significantly higher sensitivity than conventional CT for evaluating mandibular marrow invasion (97.2% vs. 80.6%, p = 0.031). In the evaluation of mandibular canal involvement, SCT showed significantly higher specificity than MRI (95.9% vs. 81.6%, p = 0.016). Furthermore, SCT demonstrated the highest correlation with pathological bone invasion depth (correlation coefficients: CT = 0.933, SCT = 0.950, MRI = 0.908; all p < 0.05). These results suggest that SCT is more effective than conventional imaging for diagnosing mandibular bone invasion and may be a useful modality for the pretreatment diagnosis of head and neck cancer. 3 Laryngoscope, 2024.

Comparison between The Efficacy of Concurrent Chemo-Radiation with Gemcitabine Followed by Intracavitary Radiotherapy in Patients with Locally Advanced Cervical Carcinoma

Introduction: Commonest threatening cancer in our Asian round is Cervical cancer. Currently, platinum-based concurrent chemo-radiation therapy is the standard of care for locally advanced cervical cancer but treatment results are disappointing, particularly for women with bulky tumors. To improve this result, several non-platinum-based agents with concurrent chemo-radiation have been evolved. Material and Methods: This was a quasi-experimental study, where 33 patients with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study from the Radiation Oncology Department of Rajshahi Medical College Hospital from April 2019 to March 2020. Duration of the study was 2 years. All patients received 150 mg/m² of Gemcitabine weekly along with external beam radiation therapy (EBRT). EBRT dose was 50 Gy in 25 daily fractions followed by intracavitary radiotherapy (ICRT) of 21 Gy in 3 fractions. Results: The mean patient age was 45.4 years. Most patients were in stage IIB (59.1%) with moderately differentiated tumors (62.1%). After three months of treatment, 81.8% showed complete response, 12.1% partial response, and 6.1% disease progression. Grade 2 and 3 hematological toxicities were common, including anemia (60.6% grade 2; 24.2% grade 3) and neutropenia (24.2% grade 2; 6.1% grade 3). Other side effects included diarrhea (42.4%), proctitis (36.4%), skin toxicity (45.5%), mild renal toxicity (3%), and grade 2 cystitis (9.1%). Conclusion: Gemcitabine-based concurrent chemo-radiation is a potential alternative for patients contraindicated for Cisplatin. However, larger randomized studies are needed to confirm its safety and efficacy.

Regulation of Tumor Growth and Invasion in Oral Squamous Cell Carcinoma by the Tumor Microenvironment Through the Enhancement of IGFBP-3 Expression.

Accumulated evidence indicates that interactions among various stromal cells within the tumor microenvironment (TME) significantly influence cancer progression. Oral cancers not diagnosed at early stages are associated with low five-year survival rates, highlighting the need for substantial improvements in patient outcomes. Understanding the interactions between cancer cells and the tumor microenvironment is crucial for identifying methods and developing treatment strategies that more effectively inhibit tumor progression and metastasis. This study investigated the roles of cancer-associated fibroblasts (CAFs) and THP-1 monocytes in tumor growth and invasion, observing changes in cancer biological characteristics through interactions with stromal cells. HSC2 oral squamous cell carcinoma (OSCC) cells were co-cultured with normal fibroblasts (NF), cancer-associated fibroblasts (CAF), or THP-1 cells. Changes in cancer cell invasion were investigated using Matrigel-coated transwell assays, collagen-based dermal equivalent assays, and in vivo mouse studies. HSC2 cells co-cultured with CAFs or THP-1 exhibited increased invasion compared to those co-cultured with normal fibroblasts (NF) in the dermal equivalent. In a mouse gingival xenograft model, cancer cells co-implanted with CAFs or THP-1 showed significantly increased tumor growth compared to those co-implanted with NF. Micro-CT (μCT) analysis revealed significant alveolar bone resorption around the mandible in tumors grown with CAFs or THP-1 cells. Conditioned media (CM) from CAFs or THP-1 significantly increased HSC2 invasion and migration, an effect that was inhibited by the protein secretion inhibitor Brefeldin (BFA). Furthermore, QuantSeq 3' mRNA sequencing indicated increased expression of IGFBP3, closely associated with cancer invasion, in HSC2 cells co-cultured with CAFs or THP-1. These findings suggest that cancer cells enhance their invasive characteristics through close interactions with the surrounding stromal cells.

Actinic keratosis with severe dysplasia and Bowen disease represent distinct pathways of intraepidermal squamous neoplasia: an immunohistochemical study

Intraepidermal squamous neoplasia is a precursor to invasive cutaneous squamous cell carcinoma. The most common type of intraepidermal squamous neoplasia is actinic keratosis (AK), although there is compelling clinicopathological evidence of a second distinct pattern of squamous dysplasia termed Bowen disease (BD). The distinction between these pathways of dysplasia has been inconsistently delineated in the literature.To further investigate the biological differences between AK and BD, a cohort of cases of intraepidermal squamous dysplasia including AK with mild/moderate dysplasia (n=26), AK with severe dysplasia (n=21) and BD (n=47) was prospectively collected. Immunohistochemistry was utilised to assess the protein expression of major tumour suppressor genes including p16, RB1 and p53.Most cases of BD showed complete loss of RB-1 (∼80%), strong and diffuse positive staining for p16 (∼80%), and mutant pattern (diffusely positive or completely negative) of p53 (∼79%). However, lesions of AK showed loss of RB-1 in only 6%, strong and diffuse positive staining for p16 in 4% and mutant pattern of p53 in 85% of case (p<0.001).The statistically significant difference in RB-1 and p16 expression between AK and BD confirms that the two morphologically distinct types of intraepidermal squamous neoplasia differ in protein expression of major tumour suppressor genes and provide evidence that they represent two distinct genomic pathways of squamous neoplasia. Recognition of clinical and genomic differences between different pathways of squamous neoplasia could potentially have an important role in predicting the biological behaviour and treatment of advanced tumours arising from these precursor lesions.

Surgical Margin and Other Prognostic Factors of Invasive Vulvar Squamous Cell Carcinoma: A Clinicopathological Mono-center Study

Surgical Margin and Other Prognostic Factors of Invasive Vulvar Squamous Cell Carcinoma: A Clinicopathological Mono-center Study

422 TrkB is a potential therapeutic target for invasive cutaneous squamous cell carcinoma

422 TrkB is a potential therapeutic target for invasive cutaneous squamous cell carcinoma

Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD+/SIRT1 Pathway

Actinic keratosis (AK) is a precursor to invasive squamous cell carcinoma, making early diagnosis and treatment essential to prevent progression. Among available therapeutic options, nicotinamide (NAM) has shown potential in reducing AK progression. NAM is a precursor of nicotinamide adenine dinucleotide (NAD+), which activates sirtuin (SIRT)1, a protein with anti-cancer properties. Although the role of SIRT1 in AK is still debated, no data currently exist on the systemic modulation of this protein in AK. Therefore, this study aims to evaluate whether NAM, by increasing serum NAD+ levels, may promote SIRT1 activation in peripheral blood mononuclear cells (PBMCs) in AK patients. Thirty patients were enrolled and treated with NAM for 24 months. Hematological, biochemical, and skin condition assessments were conducted, alongside the measurement of SIRT1 and NAD+ levels. A decrease in basophils, monocytes, total cholesterol, and blood glucose levels was observed in the study group, along with a reduction in AK lesions. Notably, NAM treatment significantly enhanced serum NAD+ levels, and nuclear SIRT1 activity in PBMCs. In conclusion, NAM administration significantly reduced AK progression in a NAD+/SIRT1-dependent manner, supporting its role as a chemopreventive agent in AK management.

Pre-metastatic niche in oral squamous cell carcinoma: Insights from a transcriptomic meta-analysis

Primary tumors can precondition a pre-metastatic niche, promoting the colonization of circulating neoplastic cells and influencing the secondary tumor microenvironment. Nevertheless, the mechanisms underlying the formation of this niche, as well as perineural invasion in oral squamous cell carcinoma (OSCC), are not well-elucidated. The study aims to identify differentially expressed genes (DEGs) and related pathways associated with pre-metastatic niche and perineural invasion in OSCC. We evaluated metastatic and non-metastatic primary tumor samples, healthy oral tissues, OSCC samples, metastatic lymph nodes from patients with OSCC, and normal lymph node samples. The GEO2R tool was applied to identify mRNAs differentially expressed between tissues exhibiting features of a pre-metastatic niche and normal tissue samples, including selected non-metastatic and metastatic OSCC samples. We also performed an analysis of perineural invasion-negative and perineural invasion-positive tumor samples. Our data revealed that SERPINE1, SPP1, CALCA, and MMP13 genes were upregulated. These upregulated genes are associated with several cancer-related pathways, while downregulated genes are mainly associated with immune responses, axon guidance, and the neurotrophin signaling pathway. Given the upregulation of the circadian rhythm pathway in metastatic lymph nodes, we also performed a correlation analysis that allows users to compute function-specific parameters, with resulting figures dynamically displayed to conveniently access the tumor&amp;rsquo;s immunological, clinical, and genomic features. Downregulation of the circadian rhythm gene PER3 and upregulation of Bhlhe40 were associated with poor survival outcomes. In conclusion, we postulate that during lymph node invasion, OSCCs activate axonal guidance genes, such as SERPENE1, L1AM, CXCR4, and SPP1. As neoplastic cells establish themselves, circadian rhythm genes are upregulated, contributing to immune evasion and promoting tumor growth.

Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC)

Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC)

Squamous Cells in Thyroid Cytology and Their Clinical Significance: A Multi-Institutional Study.

Squamous cells are uncommon in thyroid fine needle aspirations (FNAs) presenting diagnostic challenges. We report our multi-institutional experience. The electronic data were searched for thyroid FNAs containing squamous cells at the Johns Hopkins Medicine, New York University Langone Hospital, United States, and Fimlab Laboratories, Finland (2001-2023). The patients' demographics, clinical history, and pathologic diagnosis were recorded. One hundred and seven cases (103 patients) were identified 35 males and 68 females (median age 58 years). Forty-eight cases (44.9%) were malignant, primary carcinomas with squamous features, such as anaplastic thyroid carcinoma (ATC), and metastatic or directly invasive squamous cell carcinomas (SqCC) including oral, oropharyngeal (HPV-related), esophageal, and laryngeal SqCC. Twenty-seven cases (25.2%) contained benign squamous cells with cystic background, suggestive of developmental cysts. Nineteen cases (17.8%) contained metaplastic benign squamous cells within an adenomatoid nodule. Seven cases (6.5%) contained atypical squamous cells. Four cases (3.7%) showed squamous cells with bacterial or fungal organisms, suggestive of esophageal fistula/diverticulum, and two cases (1.9%) contained benign squamous cells with unknown source. Thirty-six cases had surgical follow-up, 33 (91.7%) were concordant (23 metastatic or directly invasive SqCC, 8 undifferentiated/ATC, and 10 papillary thyroid carcinoma). Ancillary studies were used confirming HPV-related SqCC, or therapeutic targets (BRAF V600E), with highly variable staining in ATC. Squamous cells in thyroid FNAs carry a broad differential diagnosis with variable prognoses. It is crucial to interpret squamous cells in the context of clinical and radiographic findings for optimal patient care.

Hypoxia combined with radiation reverses migration and invasion of head and neck squamous cell carcinoma by remodeling extracellular vesicle‐mediated transfer of miR‐23b‐5p from cancer‐associated fibroblasts

AbstractBackgroundCancer‐associated fibroblasts (CAFs), the main matrix components in the tumor microenvironment (TME), play a crucial role in tumor progression. Extracellular vesicles (EVs) as main mediators in intercellular communication can be regulated by hypoxia or radiation.MethodsCAFs were extracted from head and neck squamous cell carcinoma (HNSCC) tissues and CAF‐derived EVs were collected by ultracentrifugation. Bioinformatics analysis determined the role of poly (U)‐specific endonuclease (ENDOU) on HNSCC progression and confirmed that ENDOU inhibited HNSCC progression by overexpressing ENDOU in HNSCC. Dual‐luciferase activity report assay confirmed that miR‐23b‐5p was involved in the regulation of ENDOU expression. The migration and invasion of HNSCC cells were verified by transwell assay. Furthermore, tumor‐bearing mouse models were used to demonstrate the potential of EVs loaded with miR‐23b‐5p in HNSCC to promote tumor progression.ResultsOur results showed that ENDOU was downregulated in HNSCC and inhibited HNSCC migration and invasion. Hypoxia and radiotherapy reversed CAF‐derived EVs to promote migration and invasion of HNSCC. Mechanically, hypoxia and radiation downregulated miR‐23b‐5p in CAF‐derived EVs and then restored ENDOU expression in HNSCC. Finally, CAF‐derived EVs carrying miR‐23b‐5p promoted the progression of HNSCC cells in vivo by regulating ENDOU expression.ConclusionThis study demonstrated that hypoxia combined with radiation reverses the promoting effect of CAFs on HNSCC migration and invasion by reducing the delivery of miR‐23b‐5p by CAF‐derived EVs to decrease the inhibitory effect of ENDOU expression in HNSCC. The results provide a new perspective for better understanding the role of stromal components in TME in tumor regulation. Furthermore, the results provide a strong basis for the possibility of ENDOU as a biomarker for HNSCC.

Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance.

Histone lysine lactylation (Kla) plays a vital role in cancer progression. However, the prognostic value of histone Kla in oral squamous cell carcinoma (OSCC) remains unclear. OSCC RNA expression data were obtained from the TCGA and GEO databases. We explored the prognostic value of histone Kla in OSCC via constructing a Cox model and determined the role of Kla in OSCC drug susceptibility and tumor microenvironment (TME). In addition, the biological roles of candidate biomarkers were identified. A total of 1223 Kla-specific genes were obtained, with 228 DEKlaGs in OSCC. GO and KEGG enrichment analyses suggested that DEKlaGs contributed to inflammatory and cancer progression. A Cox model in accordance with BCAM, CGNL1, DGKG, and OLR1 could predict OSCC patient prognosis accurately. Subsequently, Kla-induced prognostic genes were identified to play a crucial role in OSCC drug therapy and TME. Moreover, BCAM was identified as a biomarker that promoted OSCC invasion, angiogenesis, and chemotherapy resistance. Kla was identified to be associated with OSCC prognosis, drug therapy, and TME. Histone Kla-induced BCAM was identified to play a crucial role during OSCC progression, suggesting that Kla is promising to be a novel therapeutic target for OSCC.

Prediction of preoperative lymph-vascular space invasion and survival outcomes of cervical squamous cell carcinoma by utilizing 18 F-FDG PET/CT imaging at early stage.

To establish nomograms for predicting preoperative lymph-vascular space invasion (LVSI) and survival outcomes of cervical squamous cell carcinoma (CSCC) based on PET/CT radiomics. One hundred and twenty-three patients with CSCC and LVSI status were enrolled retrospectively. Independent predictors of LVSI were identified through clinicopathological factors and PET/CT metabolic parameters. We extracted 1316 features from PET and CT volume of interest, respectively. Additionally, four models (PET-RS: radiomic signature of PET only; CT-RS: radiomic signature of CT only; PET/CT-RS + clinical data; PET/CT-RS: radiomic signature of PET and CT) were established to predict LVSI status. Calculation of radiomics scores of PET/CT was executed for assessment of the survival outcomes, followed by development of nomograms with radiomics (NR) or without radiomics (NWR). One hundred and twenty-three patients with pathologically confirmed CSCC had been categorized into two sets (training and testing sets). It was found that only maximum standardized uptake value (SUV max ) and squamous cell carcinoma antigen were independent predictors of LVSI. Meanwhile, the PET/CT-RS + clinical data outperformed the other three models in the training set [area under the curve (AUC): 0.91 vs. 0.861 vs. 0.81 vs. 0.814] and the testing set (AUC: 0.885 vs. 0.857 vs. 0.783 vs. 0.798). Additionally, SUV max and LVSI had been demonstrated to be independent prognostic indicators for progression-free survival and overall survival. Decision curve analysis and calibration curve indicated that NRs were superior to NWRs. The survival outcomes were assessed. PET/CT-based radiomic signature nomogram enables a new method for preoperative prediction of LVSI and survival prognosis for patients with CSCC.

Validation of lymphovascular invasion as a predictor of lymph-node invasion in squamous cell carcinoma of the penis.

The aim of this study was to validate lymphovascular invasion (LVI) as a predictor of lymph-node invasion (LNI) in squamous cell carcinoma of the penis (SCCP). Within the Surveillance, Epidemiology, and End Results database (2010-2020), we identified SCCP patients who underwent lymphadenectomy with known LVI status. Univariable logistic regression models (LRMs) addressed LNI. Harrell's concordance index (c-index) quantified accuracy after 2000 bootstrap resamples for internal validation. Multivariable LRMs included the most informative, statistically significant predictors. Subgroup analyses were repeated in organ-confined (T1b-T2) and non-organ confined (T3-T4) stages. Of 586 SCCP patients, 219 (37%) had LVI. LVI was associated with higher rate of LNI (66 vs. 43%; P<0.001). Positive predictive value of LVI was 66 vs. 57% for negative predictive value. In multivariable LRMs, LVI independently predicted LNI (Odds ratio [OR]: 2.41; P<0.001). Bootstrap-adjusted c-index of multivariable model was 0.570 without LVI vs. 0.639 with LVI. In subgroup analyses, LVI independently predicted LNI in organ-confined (OR: 2.23; P<0.001) and in non-organ confined stages (OR: 3.10; P<0.001). In subgroup analyses, addition of LVI increased c-index from 0.530 to 0.595 in organ-confined and from 0.599 to 0.682 in non-organ confined. The current study validates LVI as an independent predictor of LNI in SCCP. LVI increases the accuracy of LNI predictions in the overall cohort as well as in organ-confined and non-organ confined stages. However, stage and grade even with the added consideration of LVI are not accurate enough to provide LNI prediction in individual patients.

Podoplanin expression in various types of oral dysplasia and oral squamous cell carcinoma

ObjectiveThis study was aimed at investigating the roles of podoplanin (PDPN) as a marker associated with malignant development, progression, and poor prognosis in oral leukoplakia and various forms of oral squamous cell carcinoma (OSCC), particularly in relation to the extent of invasion. MethodsImmunohistochemical analysis of PDPN was conducted on 77 histologically confirmed, formalin-fixed, paraffin-embedded samples representing various degrees of OSCC invasion and dysplasia grades. ResultsThe samples were analyzed with Fisher's exact test and the Kruskal–Wallis test. Significant associations between sample type and the intensity, percentage, distribution, location, inflammation, and lymphatic vessel involvement according to staining were observed (p < 0.05). The PDPN staining score progressively increased from mild dysplasia to carcinoma in situ within the dysplasia classification, whereas in the OSCC classification, the highest overexpression was observed in the well-differentiated group. ConclusionEarly invasive OSCC exhibited more aggressive behavior than micro-invasive OSCC, although both were less aggressive than invasive OSCC. These findings may aid in improving prognostic accuracy and informing treatment strategies.

Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma.

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14-20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion. Methods: Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival. Results/Conclusions: In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets.

Molecular and tumor microenvironmental characterization of HPV-negative invasive squamous cell carcinoma of the vulva

Molecular and tumor microenvironmental characterization of HPV-negative invasive squamous cell carcinoma of the vulva

CHRDL1 inhibits OSCC metastasis via MAPK signaling-mediated inhibition of MED29

BackgroundCHRDL1 belongs to a novel class of mRNA molecules. Nonetheless, the specific biological functions and underlying mechanisms of CHRDL1 in oral squamous cell carcinoma (OSCC) remain largely unexplored.MethodsRT-qPCR and immunohistochemical staining were employed to assess the mRNA and protein expression levels of the MED29 gene in clinical samples of OSCC. Additionally, RT-qPCR and Western Blot analyses were conducted to investigate the mRNA and protein expression levels of the MED29 gene specifically in OSCC. The impact of MED29 on epithelial-mesenchymal transition (EMT), invasion, and migration of OSCC was evaluated through scratch assay, transwell assay, and immunofluorescence staining. Furthermore, wound healing assay and Transwell assay were utilized to examine whether CHRDL1 influences the malignant behavior of OSCC by modulating MED29 in vitro. The regulatory role of CHRDL1 on MED29 was further elucidated in vivo through a tail vein lung metastasis model in nude mice.ResultsMED29 expression was elevated in tumor tissues of OSCC patients compared with adjacent cancer tissues. Moreover, in CAL27 and SCC25 cell lines, MED29 was upregulated and associated with increased cell migration and invasion abilities. Overexpression of MED29 facilitated EMT in OSCC cell lines, whereas knockdown of MED29 impeded EMT, resulting in diminished cell migration and invasion capacities. CHRDL1 exerted inhibitory effects on the expression of MED29, thereby suppressing EMT progression and consequently restraining the invasion and migration of OSCC cells. Furthermore, CHRDL1 mediated the inhibition of migration of OSCC cell lines to the OSCC through its regulation of MED29.ConclusionsMED29 facilitated the epithelial-mesenchymal transition process in OSCC, thereby promoting migration and invasion. On the other hand, CHRDL1 exerted inhibitory effects on the invasion and metastasis of OSCC by suppressing MED29 through the inhibition of the MAPK signaling pathway.

Association Between Depth of Invasion and Tumor Stages in Oral Squamous Cell Carcinoma

Background: Depth of Invasion (DOI) in Oral Squamous Cell Carcinoma (OSCC) is an important factor of nodal metastasis and also aids with diagnosis, treatment planning, and prognostic assessments. The study’s objective was to find the association between DOI and Tumor Stages in OSCC patients. Method: This is a cross-sectional study. 150 histologically verified biopsies of OSCC patients were retrieved from Ziauddin Hospital’s Department of Histopathology from March 2023 to 2024. The sampling technique was consecutive. Specimens were preserved in formalin, embedded in paraffin, and stained with Hematoxylin and Eosin. Oral cancer was graded according to WHO requirements and the American Joint Committee on Cancer (AJCC) classification (TNM classification) for staging. Digital microscopic imaging determined the (DOI), as defined by the AJCC eighth edition. Statistical analysis was conducted using IBM SPSS version 24. DOI, PNI, and LVI were compared with Tumor Grade, Tumor Size, Nodal Stage, and Tumor Stage by using Chi-square/Fisher’s exact test. P-value &lt; 0.05 is considered statistically significant. Results: Buccal mucosa (59.3%) and tongue (18.0%) were the most common sites. The majority of tumors were moderately differentiated (96.7%), with over half having a DOI &gt;10mm (50.7%) and T4 tumor size being most prevalent (39.3%). DOI is statistically significantly associated with tumor grade (p-value = 0.011) while not significantly associated with tumor size, nodal stage, and tumor stage (p=value &gt; 0.05). Conclusion: Our study highlights the insignificant association between DOI and tumor size, nodal stage, or overall tumor stage, but emphasizes its importance in assessing and staging OSCCC, distinguishing superficial and deeply invasive tumors, and improving patient outcomes.

Comparative Study of Cutaneous Squamous Cell Carcinogenesis in Different Hairless Murine Models

Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis.