Background The most prevalent form of head-neck cancer is squamous cell carcinoma (SCC). Apart from all sites like the tongue, labial mucosa, and buccal mucosa, the prevalence of oral squamous cell carcinoma (OSCC) is more common in gingivobuccal sulcus due to the habit of keeping tobacco quid. With regards to anatomical relationships in the mouth and proximity to bone, OSCC invades the maxilla and mandible. However, bone invasion significantly influences the pathological staging of OSCC. Histological parameters such as Brandwein-Gensler worst pattern of invasion (WPOI), lymphocytic host response (LHR), and perineural invasion (PNI) hold significance for determining the need for adjuvant therapy. This study aims to correlate Brandwein-Gensler Criteria (BGC) with bone invasion and also to include the bone invasion criteria as a prognostic parameter in OSCC. This study aimed to assess bone invasion and correlate it with Brandwein-Gensler criteria in OSCC. Methods The research was conducted retrospectively, analyzing 65 cases of OSCC that underwent surgical intervention. Data was gathered from the Oral Pathology department\'s archives at Sharad Pawar Dental College (SPDC), Wardha. Pathologists assessed bone invasion without the knowledge of other factors to minimize bias. Subsequently, the cases were classified into well-differentiated (WDSCC), moderately differentiated (MDSCC), and poorly differentiated squamous cell carcinomas (PDSCC) based on histological grading, followed by the evaluation of WPOI, LHR, and PNI using the Brandwein-Gensler risk scoring system. Results This study found a notable association between bone invasion and BGC, with a calculated significance level of p = 0.047. LHR shows patterns as 1, 2, and 3. There were five (7.6%) cases with pattern III, 45 (69.23%) cases with pattern II, and 15 (23.08%) cases with pattern I. Similarly, PNI is scored as 0, 1, and 3. There were seven (10.77%) cases with score 3, 17 (26.15%) with score 1, and 41 (63.03%) with score 0. In the case of the WOPI, which is classified as patterns I to V, there were seven (10.77%) cases with pattern V, 27 (41.54%) cases with pattern IV, 23 (35.38%) cases with pattern III, and eight (12.231%) cases with pattern II, whereas no cases were noted with pattern I. Conclusion Although bone invasion and BGC are independent parameters, the BGC score should be considered in treatment planning. Patients with bone invasion and those with a higher BGC score should be strongly considered for adjuvant treatment.

The aim of this study was to investigate the correlation between pre-treatment inflammatory biomarkers and the post-operative depth of invasion (DOI) and worst pattern of invasion (WPOI) in early-stage oral tongue squamous cell carcinoma (OTSCC) by means of positive sentinel lymph node biopsy (SLNB). A retrospective analysis of patients affected by cN0 T1-T2 OTSCC who had undergone an SLNB at the National Cancer Institute of Naples was performed. The patients were studied using an evaluation of the pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and a histopathological analysis of the DOI and WPOI. The statistical analysis showed that among the prognostic biomarkers, the NLR was a significant predictor of high WPOI values (p = 0.002). The cut-off NLR value was 2.52 with a probability of developing a positive sentinel lymph node biopsy (SLNB) of 30.3%. In contrast, the DOI value was 5.20 with a probability of developing a positive SLNB of 31.82%. Regarding the WPOI, increasing the WPOI class increased the likelihood of a positive SLNB occurrence, and a positive significant correlation was found between the WPOI and SLNB (Csp = 0.342; p < 0.001). Pre-treatment NLR, together with post-surgical DOI and WPOI, can be a reliable predictor of occult neck metastasis in patients affected by early-stage OTSCC with a clinically negative neck. Further prospective studies with a larger series will be needed to confirm the results obtained and to better define the NLR, WPOI and DOI cut-off values in order for elective neck dissection to be recommended in relation to a clinically negative neck.

The C-C motif chemokine ligand 22 (CCL22) chemokine is produced by M2-like tumor-associated macrophages (TAMs) in the tumor microenvironment. Chemokine C-C motif receptor 4 (CCR4), the CCL22 receptor, on T helper2 (Th2) cells leads to a Th2 cytokine-dominant environment. In our previous study, lymph node metastasis was the main predictor of tongue squamous cell carcinoma (SCC) via CCL22. Therefore, the present study aimed to investigate the effects of CCL22 and a Th2 cytokine-predominant tumor microenvironment on vascular endothelial growth factor (VEGF)-C expression and lymphangiogenesis. The post-operative courses of 110 patients with early-stage tongue SCC with a histopathological diagnosis based on the 8th TNM classification were followed up (mean/median follow-up time, 47.1/42.0 months) from surgery until death or the last follow-up visit, and subsequent lymph node relapse was assessed. Lymphangiogenesis and the immunohistochemical expression of several markers (CCL22, CCR4 and VEGF-C) were evaluated. The Kaplan-Meier method was used to plot lymph node relapse-free survival and overall survival curves, which were compared using the log-rank test. In vitro, the association between CCL22 and VEGF-C by interleukin (IL)-4/signal transducer and activator of transcription 6 (STAT6) stimulation was examined. Lymphangiogenesis was significantly associated with lymph node relapse (P<0.001) and a CCL22+ macrophage ratio (P<0.001). CCL22+ TAMs were positive for VEGF-C and surrounded by CCR4+ cells. Additionally, VEGF-C expression was increased in IL-4/STAT6-stimulated macrophages. In addition, the STAT6 signaling pathway was activated in the SCC cells in the deeply invaded part of the tumor along with the aggregated macrophages. In conclusion, TAM CCL22 expression led to lymph node relapse via VEGF-C expression within the tumor microenvironment and the IL-4/STAT6 signaling pathway in early stage tongue SCC. Additionally, the worst pattern of invasion and depth of invasion were revealed to be useful parameters for lymph node relapse in patients with tongue SCC. The present study suggested that CCL22 contributed to the role of M2-like differentiated TAMs in prognosis and lymph node relapse via IL-4/STAT6 and VEGF. The IL-4/STAT6 signaling pathway may be a new molecular target for tongue SCC.

Oral squamous cell carcinoma (OSCC) is a highly lethal cancer in the world, and the prognosis of OSCC is poor with a 60% 5-year survival rate in recent decades. Here, we introduced a novel secretory and acid glycoprotein with cysteine rich (secreted protein acidic and rich in cysteine, SPARC), which is correlated with the worst pattern of invasion (WPOI) and prognosis of OSCC. SPARC expression levels were measured in OSCC tissues and normal tissues using quantitative polymerase chain reaction and immunohistochemistry. The influence of SPARC on cell proliferation was examined by cell counting kit-8, colony formation, and Edu tests. Then, the effect of SPARC on the metastasis of OSCC cells was detected by wound healing and transwell migration assays. Next, the biologic characteristics of SPARC shared by STRING were analyzed. Furthermore, the underlying mechanisms were confirmed by western blot analysis. SPARC revealed higher expression in OSCC tissues than nontumor tissues. Higher SPARC expression was correlated with poorer tumor differentiation, poorer WPOI pattern, and significantly and shorter overall survival. Knockdown SPARC significantly restrained OSCC cell growth, migration, and invasion. In addition, bioinformatics analysis found SPARC had a coexpression network with the platelet-derived growth factor-B (PDGFB) and PI3K/AKT signaling pathways with minimal false discovery rate. Furthermore, SPARC promotes OSCC cells metastasis by regulating the expressions of PDGFB, PDGFRβ, p-PDGFRβ , and the PI3K/AKT pathway. Higher SPARC expression was positively correlated with poor WPOI and differentiation in OSCC. SPARC activates the PI3K/AKT/PDGFB/PDGFRβ axis to promote proliferation and metastasis by OSCC cell lines. Therefore, SPARC may be a potential therapeutic target for patients with OSCC.