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Background: ANXA5, a notable tumor marker, displays irregular expression in diverse solid cancers, and links to local recurrence and metastasis rates. We aimed study the expression of ANXA5 in oral squamous cell carcinoma (OSCC) and its diagnostic and prognostic values. Methods: 520 head and neck squamous cell carcinoma (HNSCC) patients in TCGA database and 124 OSCC patients in Nanjing stomatology hospital were enrolled in our study. Immunohistochemical analyses were performed using ANXA5 antibodies. Chi‐square test was used to analyze the clinicopathological features. Survival rates were determined using the Kaplan–Meier method and log‐rank test. Results: Our results showed significantly elevated ANXA5 at the gene and protein levels in HNSCC and OSCC compared to non‐tumor tissues. Histopathologically, ANXA5 was broadly present in OSCC tumor cells and fibroblast‐like cells but absent in tumor‐infiltrating lymphocytes, particularly at the invasive tumor front. Patients exhibiting high ANXA5 expression in these cells demonstrated poor differentiation, aggressive invasion patterns, and heightened lymph node metastasis risk, contributing to poorer postoperative outcomes. Remarkably, ANXA5 in fibroblast‐like cells emerged as an independent risk factor impacting survival in OSCC patients. Gene set enrichment analysis (GSEA) highlighted ANXA5's involvement in key pathways like epithelial‐mesenchymal transformation (EMT), TGF‐beta signaling, and hypoxia, which correlated with adverse clinical outcomes in OSCC. Conclusion: ANXA5 emerges as a significant prognostic biomarker for OSCC, potentially influencing its metastasis via the EMT pathway. [ABSTRACT FROM AUTHOR]

Background Tumor budding is defined as a single cell or a cluster of up to five tumor cells at the invasion front of all oral squamous cell carcinoma (OSCC) cases. Tumor budding is considered as a marker of many important events in oral carcinoma, including the epithelial-mesenchymal transition, invasion, metastasis, and for further prognosis. Methods A total of 30 clinically and histopathologically diagnosed cases of OSCC were retrieved from the archival of the Department of Oral Pathology and Microbiology. After assessing the sections for the presence of tumor budding (TB), it is further categorized into high-intensity TB and low-intensity TB. Results We found a strong association between lymph node metastasis and histopathological grading in the current study. There was no association between TB and a patient’s survival rate. Conclusions This study emphasizes the significance of tumor budding, its relevance to prognosis, and reproducibility, as well as the significance of its evaluation and incorporation into routine surgical pathology practice in the management of OSCC. As a result, we believe that tumor budding is a crucial factor in determining tumor behavior.

Background: Tumor budding (TB) is defined as a single cell or a cluster of up to five tumor cells at the invasion front of all oral squamous cell carcinoma (OSCC) cases. Tumor budding is considered a marker of many important events in oral carcinoma, including the epithelial-mesenchymal transition, invasion, metastasis, and for further prognosis. Methods: A total of 30 clinically and histopathologically diagnosed cases of OSCC were retrieved from the archival of the Department of Oral Pathology and Microbiology. After assessing the sections for the presence of TB, it is further categorized into high-intensity TB and low-intensity TB. Results: We found a strong association between lymph node metastasis, lymph node metastasis, and histopathological grading in the current study. There was no association between TB and a patient's survival rate. Conclusions: This study emphasizes the significance of tumor budding, its relevance to prognosis, and reproducibility, as well as the significance of its evaluation and incorporation into routine surgical pathology practice in the management of OSCC. As a result, we believe that tumor budding is a crucial factor in determining tumor behavior.

Aims: Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological characteristics, and the individual histological characteristics of the tumors are poorly understood. Therefore, calculating the proportion of tumor cells in different regions that allow assessment of the prognostic outcomes for OSCC patients would be of great clinical significance. Methods and Results: We established an open‐source software‐based analytic pipeline that defines the inner tumor and invasive tumor front (ITF) in pancytokeratin‐stained whole slide images (WSIs) and quantifies the tumor‐stroma ratio (TSR) within the two regions. We applied this method to 114 patients with OSCC and predicted patient prognosis by the TSR. The proportion of tumor area in the inner tumor was generally higher than that in the ITF (p < 0.0001). TSR was an independent prognostic factor for overall survival (OS) (p = 0.016), disease‐free survival (DFS) (p = 0.026), and relapse‐free survival (RFS) (p = 0.037) in inner tumor, and TSR was an independent prognostic factor for OS (p = 0.00052), DFS (p = 0.035), and metastasis‐free survival (MFS) (p = 0.038) in the ITF. Tumor‐low status was associated with poorer prognosis. There was a significant correlation between the TSR and perineural invasion (PNI) in the inner tumor (p = 0.009). Conclusions: The histopathological characteristics of different regions of OSCC may be used to develop the potential prognostic markers. The TSR of the inner tumor is more targeted in predicting prognosis and accurately assesses the risk of PNI+. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a significant public health problem in India, accounting to 30% of all cancers with a worrying rise in incidence and related mortality. Invasive tumor front (ITF) of OSCC has been an area of histopathologic research interest, where parameters like tumor budding (TB), mode of invasion (MOI) and lymphocytic host response (LHR) are being evaluated extensively. Objectives: The aim is to study and evaluate the possible association of ITF histological parameters such as TB, LHR and MOI with known clinicopathological prognostic factors in cases of OSCC. Subjects and Methods: We reviewed and analyzed 69 cases of OSCC for routine clinicopathological parameters, TB, MOI and LHR for any significant correlation (P < 0.05 by Chi-square test) with each other and with outcome in cases where follow-up was available. Results: TB correlated significantly with histological grade, worst pattern of invasion (WPOI), Lymphnodal involvement (LNI), Lymphovascular invasion (LVI), Perineural invasion (PNI) and age; MOI correlated with WPOI, LNI, LVI and PNI; and LHR significantly correlated with WPOI, PNI, Tumor size (pT) and outcome. TB showed a strong correlation with MOI (P < 0.001) and LHR; and no significant association was noted between LHR and MOI. Among all the clinicopathological parameters, depth of invasion, pT, WPOI, PNI and LHR showed significant correlation with outcome. Conclusion: TB, MOI and LHR showed good correlation with established parameters and as they are easy and helps in prognostication, they should be included in routine histopathological reporting guidelines. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-β (TGF-β) exerts its versatile function (oncogenic or tumor suppressive role) during the carcinogenesis in tumor microenvironment-dependent manner. Considering the tumor heterogeneity, spatial and temporal distribution of TGF-β in oral squamous cell carcinoma (OSCC) remained to be elucidated.Methods: Formalin-fixed, paraffin-embedded sections derived from 73 patients with OSCC were immunostained, revealing expression patterns of TGF-β, both at the regions of tumor center (TC) and invasive tumor front (ITF).Results: The TGF-β levels on tumor cells, fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs) were comparable and showed to be cell-type-independent manner. Although TC regions harbored less positive staining of TGF-β than ITF in tumor cells (TGF-βTumor cell ) (89.0% vs 98.3%; P = 0.037), FLCs (TGF-βFLC ) (86.3% vs 96.6%; P = 0.043), and TILs (TGF-βTIL ) (83.6% vs 94.8%; P = 0.044), respectively, TGF-β at TC regions, not at ITF, correlated to poor clinical outcomes. At TC regions, patients with high TGF-βTumor cell had high recurrence rate, and patients with high TGF-βTIL showed inferior worst pattern of invasion. Of note, high TGF-βTumor cell at TC predicted shorter overall survival time, recurrence-free survival, and disease-free survival in patients with OSCC, whereas high TGF-βTIL had no association with survival time. Cox regression analyses indicated that tumor cell-derived TGF-β at TC was an independent risk factor for survival outcome in patients with OSCC.Conclusions: Tumor cell-derived TGF-β at TC regions, but not at ITF, could be a promising predictor for disease recurrence and poor prognosis of patients with OSCC. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has the worst prognosis and the highest immunogenic potential of all breast cancer subtypes. It is characterized by a lack of estrogen and progesterone receptors as well as HER2. A major component of the tumor microenvironment (TME) of TNBC is tumor-infiltrating lymphocytes (TILs). A chaperone heat shock protein 70 (HSP70) is involved in several pathways that enable tumour growth and progression, as well as in immune modulation. Immunohistochemical analysis of HSP70 expression in immune cells, as well as expression of immunosuppressive markers CTLA4 and PD-L1 and major TILs components: CD8, CD4 and Tregs were analyzed in the superficial and deep tumor layer of primary TNBC and compared with established clinicopathological parameters. Clinical data and surgical tissue samples from 68 TNBC patients who underwent initial surgery were included in the analysis and 36 control samples from benign breast tissue biopsies. A higher expression of TILs, CD4, CD8 and PD-L1 was found in the invasive tumor front (ITF), as compared to the tumor center (TC) (p < 0001). HSP70 positive immune cells (HSP70(+) IC) in TC were associated with adverse clinical and pathological markers: higher stage of disease (P = 0.013), higher grade (P = 0.05) and a higher pN status (P < 0.001). In addition, higher expression of HSP70(+) IC from TC was correlated with the higher expression of FOXP3(+)T cells both in ITF (N = 61, rho=0.42, p < 0.001) and in metastatic tissue from the draining lymph nodes (N = 13, rho=0.61, P = 0.026). Correlations between HSP70 immune cells expression and individual TILs components support the hypothesis of its active role in inducing immunosuppression and tumor progression. Routine determination of HSP70 expression, in immune cells of TC, may be of added value in the clinical decision-making process concerning axillary surgery. [ABSTRACT FROM AUTHOR]

Background: Recent studies have indicated that although malignant cells at the invasive tumor front, bare morphological resemblance to the cells at central portion of the tumor, their molecular character differs significantly. E-cadherin is a cell-cell adhesion molecule that connects epithelial cells. This study attempts to correlate the E-cadherin expression at the invasive tumor front with tumor differentiation along with its clinico-pathological parameters. Materials and Methods: Immunohistochemical staining with E-cadherin was carried out on archival cases of primary oral squamous cell carcinomas (n = 30). The E-cadherin expression at the invasive tumor front was analyzed and was linked to clinico-pathological parameters including patient prognosis. Results: The downregulation of E-cadherin expression at the invasive tumor edge when compared with patient's prognosis yielded a significant correlation (P = 0.041) but its correlation with the degree of differentiation determined was not significant (P = 0.27). Also, its association with tumor size and lymph node status was negative. Conclusions: Loss of E-cadherin expression at the invasive tumor front is an important event in the progression of oral squamous cell carcinomas. Tumors with a loss of expression of E-cadherin are those which had a poor prognosis [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) 40: 545–551 Background:  Tumor budding is a readily detectable histopathological feature and has been recognized as an adverse prognostic factor in several human cancers. However, the prognostic value of tumor budding in tongue squamous cell carcinoma (TSCC) has not been reported. The purpose of this study was to assess the correlation of tumor budding with the clinicopathologic features, and the known molecular biomarkers (E‐cadherin and Vimentin), as well as to evaluate its prognostic significance for TSCC. Methods:  Archival clinical samples of 230 patients with TSCC were examined for tumor budding. Immunohistochemistry analyses were performed to examine the expression of E‐cadherin and Vimentin. Statistical analyses were carried out to assess the correlation of tumor budding with clinicopathologic parameters and patient survival. The potential association between tumor budding and alterations of E‐cadherin and Vimentin expression was also assessed. Results:  Of the 230 TSCC cases examined, tumor budding was observed in 165 cases (71.7%), with a mean tumor bud count of 7.5 (range from 1 to 48 buds). High‐intensity budding (≥5 tumor buds) was observed in 111 cases (48.3%). Statistical analysis revealed that tumor budding was associated with tumor size (P < 0.05), differentiation (P < 0.05), clinical stage (P < 0.05), lymph node metastasis (P < 0.01), and correlated with reduced overall survival. In addition, significant associations were observed among tumor budding and the deregulation of E‐cadherin (P < 0.001) and Vimentin (P < 0.001). Conclusions:  Tumor budding, which associates with epithelial–mesenchymal transition, is a frequent event and appears to be an independent prognostic factor in TSCC. [ABSTRACT FROM AUTHOR]

Malignant tumor of oral cavity account for approximately 30% of all head and neck cancers and 95% of these are Oral Squamous Cell Carcinoma (OSCC). Patients with OSCC can die from failure to control the primary lesion or regional lymph node metastases. An analysis of the prognostic factors in addition to tumor, node, metastases (TNM) staging or the histopathological grading is important for predicting the prognosis and achieving a high-survival rate in these patients. The invasive tumorfront(ITF) has been defined as the most progressed, 3 to 6 tumor cell layers or detached tumor cell groups at the advancing edge of the OSCCs. The ITF frequently shows a lower degree of differentiation, migration, apoptosis and a higher grade of cellular dissociation in comparison with other parts of the tumor. The histological features of OSCC may widely differ from area to area within the same tumor and it is believed that the most useful prognostic information can be deduced from the invasive tumor front, where the deepest and presumably most aggressive cells reside. Numerous molecular events of significance for tumor spread, such as gain and loss of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation, budding and initiation of angiogenesis occur at the tumor-host interface or invasive front. This poster will discuss the significant pathologic changes occurring at the ITF and its importance in early detection and prognosis in OSCCs. [ABSTRACT FROM AUTHOR]