Search

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.

Abstract 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

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]

The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis. The purpose of this study was to integrate data on the digital patterns of reticulin fiber scaffolding and the immune cell infiltrate, transcriptomic and epigenetic profiles in aggressive uterine adenocarcinoma (uADC), uterine leiomyosarcoma (uLMS) and their respective lung metastases, with the aim of obtaining key TME biomarkers that can help improve metastatic prediction and shed light on potential therapeutic targets. Automatized algorithms were used to analyze reticulin fiber architecture and immune infiltration in colocalized regions of interest (ROIs) of 133 invasive tumor front (ITF), 89 tumor niches and 70 target tissues in a total of six paired samples of uADC and nine of uLMS. Microdissected tissue from the ITF was employed for transcriptomic and epigenetic studies in primary and metastatic tumors. Reticulin fiber scaffolding was characterized by a large and loose reticular fiber network in uADC, while dense bundles were found in uLMS. Notably, more similarities between reticulin fibers were observed in paired uLMS then paired uADCs. Transcriptomic and multiplex immunofluorescence-based immune profiling showed a higher abundance of T and B cells in primary tumor and in metastatic uADC than uLMS. Moreover, the epigenetic signature of paired samples in uADCs showed more differences than paired samples in uLMS. Some epigenetic variation was also found between the ITF of metastatic uADC and uLMS. Altogether, our data suggest a correlation between morphological and molecular changes at the ITF and the degree of aggressiveness. The use of DP tools for characterizing reticulin scaffolding and immune cell infiltration at the ITF in paired samples together with information provided by omics analyses in a large cohort will hopefully help validate novel biomarkers of tumor aggressiveness, develop new drugs and improve patient quality of life in a much more efficient way.

Background: Prognosis of oral squamous cell carcinoma (OSCC) can be predicted by evaluating both clinicopathological parameters and molecular markers. Understanding the reasons of recurrence is important to increase the morbidity and mortality of the patient. Objectives: The objectives are to study the immunoexpression of p53 and Ki-67 in recurrent and non recurrent OSCC. And correlate the clinicopathological parameters among non-recurrent and recurrent OSCC to predict the prognosis of OSCC. Methods: Clinicopathological and immunoexpression of p53 and Ki-67 at the histologically negative margin (HNM) and invasive tumor front (ITF) were assessed in 50 cases of non-recurrent and recurrent OSCC. Overall survival and disease free survival was estimated. Statistical tests like Mann Whitney U test, t Test, Pearson correlation coefficient, Kaplan Meier curve and Log Rank test were used. Results: The Labelling Index (LI) of p53 and Ki-67 was marginally higher in recurrent than in non-recurrent OSCC cases. When compared with clinicopathologic parameters, non-recurrent OSCC cases showed no significance with p53 LI in margin and ITF except for site, muscle invasion, pattern of invasion (POI) and muscle invasion, whereas in recurrent OSCC cases p53 LI in HNM and ITF did not show any statistical significance except for duration. In both groups, OS and DFS was higher in patients with lesser LI while higher in the greater LI but more number of deaths occurred in this category respectively. Conclusion: To conclude p53 and Ki-67 positivity in the HNM and ITF of non-recurrent and recurrent OSCC was seen and thus can be an important marker for identification of high and low risk individuals.

Background: The invasive tumor front (ITF) of oral squamous cell carcinoma (OSCC) and the reactive changes in regional lymph nodes (RLNs) are believed to carry integral prognostic information about the tumor's invasive capacity and insight into host immune response, respectively.Aim: This study aims to evaluate the reactivity patterns of RLNs in relation to the tumor stage, grade and various histopathological parameters at the ITF of primary tumor, in an attempt to elucidate the nature of host-immune response to tumor.Materials and Methods: Pattern of invasion (POI) using Bryne's criteria, peritumoral inflammation, and status of connective tissue (CT) stroma of 50 OSCC cases, that underwent selective neck dissection were assessed at the ITF. Immunoreactivity patterns in corresponding 450 RLNs were assessed as proposed by Tsakraklides and Ioachim. Further, 97 metastatic lymph nodes (LNs) were evaluated for degree and pattern of tumor invasion. The datasets were subjected to the Chi-square analysis.Results: There was statistically significant association (P = 0.001) of Type III and Type IV POI as well as mild peritumoral inflammation (P = 0.024) with the advanced stages of OSCC as compared to early stages. Significant association was observed between LN reactivity pattern and tumor stage (P = 0.05), with metastatic nodes exhibiting germinal center predominance (97.9%) and lymphocyte predominance (69.1%) largely observed in nonmetastatic nodes. Majority of metastatic nodes showed Grade 3 invasion (54.7%) in the form of large islands (57.7%), whereas two (2.1%) nodes were totally effaced by tumor metastasis. Statistical significance was observed between CT stroma at ITF and degree of tumor invasion in metastatic LN (P = 0.001). POI also showed significant correlation with peritumoral inflammation (P = 0.002), CT stroma (P = 0.02), and LN reactivity pattern (P = 0.03).Conclusion: This study supports the presence of a strong immunological host-tumor relationship. [ABSTRACT FROM AUTHOR]

Introduction: Pattern of invasion (POI) in scoring system of oral squamous cell carcinoma (OSCC) can predict local recurrence and overall survival rate. Argyrophilic nucleolar organizer region (AGNOR) counts are considered to reflect the biosynthetic and nucleolar activity of a cell and thus serve as an indicator of the rapidity of the cell cycle thereby indicating the proliferative index of the tumor. It is implied that higher tumor associated tissue eosinophilia (TATE) showed lesser venous invasion, lymph node metastasis and clinical recurrence. The aim of the study was to assess and evaluate the following criteria's: POI-1 to POI-4 as defined by Bryne et al. in OSCC, proliferative index by AgNOR stain and TATE with carbol chromotrope stain in OSCC, validity of POI by correlating the AgNOR proliferative index and TATE. Materials and Methods: Forty samples of formalin fixed paraffin embedded tissue blocks diagnosed of OSCC were taken for the study. Three sections were taken from a single block and then the tissues were stained differently with H & E Stain, AgNOR stain and Carbol chromotrope stain. First section stained with H & E was observed for POI and grading was done according to Bryne's criteria. The second and third sections were stained with AgNOR stain and Carbol chromotrope stain for proliferative index and TATE. One way analysis of variance was used to test the significance. Results: Mean AgNORs count increases gradually from type 1 to type 4, depicting the increase in the nucleolar proliferative index of the cells and was statistically significant. In the case of the mean eosinophilic count, type 1 shows the highest mean eosinophilic count and the count shows drastic decrease till type 3 and from type 3 to type 4 the decrease is more gradual and was statistically significant. Conclusion: The study validated that POI is a good predictor for prognosis and also can be included in grading OSCC along with routine histopathological criteria. [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: Prognosis of oral squamous cell carcinoma (OSCC) can be predicted by evaluating both clinicopathological parameters and molecular markers. Understanding the reasons of recurrence is important to increase the morbidity and mortality of the patient. Aims and Objectives: The objectives are to study the immunoexpression of p53 and Ki-67 in recurrent and non recurrent OSCC. And correlate the clinicopathological parameters among non-recurrent and recurrent OSCC to predict the prognosis of OSCC. Materials and Methods: Clinicopathological and immunoexpression of p53 and Ki-67 at the histologically negative margin (HNM) and invasive tumor front (ITF) were assessed in 50 cases of non-recurrent and recurrent OSCC. Overall survival and disease free survival was estimated. Statistical tests like Mann Whitney U test, t Test, Pearson correlation coefficient, Kaplan Meier curve and Log Rank test were used. Results: The Labelling Index (LI) of p53 and Ki-67 was marginally higher in recurrent than in non-recurrent OSCC cases. When compared with clinicopathologic parameters, non-recurrent OSCC cases showed no significance with p53 LI in margin and ITF except for site, muscle invasion, pattern of invasion (POI) and muscle invasion, whereas in recurrent OSCC cases p53 LI in HNM and ITF did not show any statistical significance except for duration. In both groups, OS and DFS was higher in patients with lesser LI while higher in the greater LI but more number of deaths occurred in this category respectively. Conclusion: To conclude p53 and Ki-67 positivity in the HNM and ITF of non-recurrent and recurrent OSCC was seen and thus can be an important marker for identification of high and low risk individuals. [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]

The treatment failure in Oral carcinoma patients is mainly due to recurrence leading to a poor prognosis. Genetically transformed cells in the adjacent mucosal area thought to be the reason for local recurrences and an invasive tumour front area is known to host the aggressive tumour cells. Hence, the study conducted to quantify and compare proliferative markers Ki-67 and MCM 2 antigens at the margins and invasive tumour front to predict recurrence and prognosis in Oral squamous cell carcinomas. The study involved paraffin tissue sections of 30 cases of recurrent, and 30 cases of non recurrent Oral squamous cell carcinomas were subjected to Immunohistochemical analysis at negative surgical margins and invasive tumour front (ITF). The mean labelling index (Li) of MCM 2 (Minichromosome Maintenance Protein 2) and Ki-67 was compared among the groups with ' t ' test to predict the recurrence and overall survival by Kaplan-meier curve and Log-rank test survival estimate. The Li of Ki-67 and MCM 2 were higher at negative margin and ITF of recurrent group compared to non recurrent OSCC group with statistically significant difference (P < 0.05) only with MCM 2. Li of MCM 2 at margin and ITF was a better predictor of overall survival than Ki-67. The overall survival was significantly lower in 43.95 months with Li of MCM 2 more than 48.2 at margin. MCM 2 is a novel marker at negative margins in predicting the recurrence and survival of Oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Vascular remodeling at the invasive tumor front (ITF) plays a critical role in progression and metastasis of triple negative breast cancer (TNBC). Therefore, there is a crucial need to characterize the vascular phenotype (i.e. changes in the structure and function of vasculature) of the ITF and tumor core (TC) in TNBC. This requires high-resolution, 3D structural and functional microvascular data that spans the ITF and TC (i.e. ∼4–5 mm from the tumor's edge). Since such data are often challenging to obtain with most conventional imaging approaches, we employed a unique "3D whole-tumor angiogenesis atlas" derived from orthotopic xenografts to characterize the vascular phenotype of the ITF and TC in TNBC. First, high-resolution (8 μm) computed tomography (CT) images of "whole-tumor" microvasculature were acquired from eight orthotopic TNBC xenografts, of which three tumors were excised at post-inoculation day 21 (i.e. early-stage) and five tumors were excised at post-inoculation day 35 (i.e. advanced-stage). These 3D morphological CT data were combined with soft tissue contrast from MRI as well as functional data generated in silico using image-based hemodynamic modeling to generate a multi-layered "angiogenesis atlas". Employing this atlas, blood vessels were first spatially stratified within the ITF (i.e. ≤1 mm from the tumor's edge) and TC (i.e. >1 mm from the tumor's edge) of each tumor xenograft. Then, a novel method was developed to visualize and characterize microvascular remodeling and perfusion changes in terms of distance from the tumor's edge. The angiogenesis atlas enabled the 3D visualization of changes in tumor vessel growth patterns, morphology and perfusion within the ITF and TC. Early and advanced stage tumors demonstrated significant differences in terms of their edge-to-center distributions for vascular surface area density, vascular length density, intervessel distance and simulated perfusion density (p ≪ 0.01). Elevated vascular length density, vascular surface area density and perfusion density along the circumference of the ITF was suggestive of a preferential spatial pattern of angiogenic growth in this tumor cohort. Finally, we demonstrated the feasibility of differentiating the vascular phenotypes of ITF and TC in these TNBC xenografts. The combination of a 3D angiogenesis atlas and image-based hemodynamic modeling heralds a new approach for characterizing the role of vascular remodeling in cancer and other diseases. • High-resolution CT-derived, 3D microvascular data from orthotopic early- and advanced-stage triple negative breast cancer (TNBC) xenografts were employed to simulate whole-tumor hemodynamics. • 3D morphological microvascular data were combined with soft tissue contrast from MRI as well as functional data generated in silico using the image-based hemodynamic modeling to generate a multi-layered "angiogenesis atlas". • This angiogenesis atlas enabled blood vessels to be spatially classified as belonging to the invasive tumor front (ITF) or tumor core (TC) for each xenograft. • The angiogenesis atlas enabled the 3D visualization of changes in tumor vessel growth patterns, morphology and perfusion within the ITF and TC. • We demonstrated the feasibility of differentiating the vascular phenotypes of ITF and TC in TNBC xenografts [ABSTRACT FROM AUTHOR]

Background and objective The invasive tumor front (ITF) refers to cells or invasive nests in the junctional region of a tumor and its host. The ITF contains the most invasive cells of a tumor, and has a high prognostic value in carcinoma. The aim of this study is to investigate the epithelial-mesenchymal transformation phenotype in ITF cells of lung squamous cell carcinoma (SCC), and analyze the relationship between clinicopathological features and clinical outcomes of patients. Methods Semiquantitative immunohistochemistry was used to examine the expression of epithelial markers (E-cadherin and β-catenin) and mesenchymal marker (vimentin) in 104 lung SCC tumor tissues. Results A decrease in E-cadherin expression in ITF cells was observed in 56 of 104 (53.8%) tumors from patients. This result was markedly lower than that of non-ITF cells, which eventually developed metastatic tumors and were also associated with death (P=0.04). Vimentin expression was observed in 44 of 104 (42.3%) ITF cells, which was much higher than that of non-ITF cells. The downregulation of E-cadherin and overexpression of vimentin were associated with tumor invasive pattern, lymphatic metastasis, and poor prognosis (P

Abstract: Aim: The aim of the present study was to: (a) analyze the nature of collagen with respect to cohesive and discohesive invasive tumor front (ITF) of oral squamous cell carcinoma (OSCC); (b) analyze the clinicopathological correlation with the nature of collagen at the ITF of OSCC; and (c) correlate the nature of collagen with Broder's and Bryne's histological grading system of OSCC. Methods: Tissue sections of 29 OSCC with ITF were stained with hematoxylin‐eosin and picrosirius red staining for evaluation under a polarized microscope. Results: Tumors with a cohesive front had a thick collagen fiber, are predominantly organized, red‐yellow in color, well packed, and show strong birefringence (P<.005). A gradual change in the nature of the collagen fiber was observed in the discohesive tumor front, where the collagen fibers were thin, disorganized, yellow‐orange to green‐yellow in color, loosely packed, and with weak birefringence (P<.005). Conclusion: A cohesive tumor front with organized collagen fibers prevents tumor invasion and metastasis. As it is inhibits an increase in tumor size, it is associated with the initial stage of tumor (I & II), whereas in a discohesive tumor front, the fibers might enhance the movement of tumor cells, resulting in invasion and metastasis. [ABSTRACT FROM AUTHOR]

Introduction: Oral squamous cell carcinoma (OSCC) accounts 94% of all malignant lesions in the oral cavity. In the assessment of OSCC, nowadays the WHO grading system has been followed widely but due to its subjectivity, investigators applied the sophisticated technique of computer-assisted image analysis in the grading of carcinoma in larynx, lungs, esophagus, and cervix to make it more objective. Aims and Objectives: Access, analyze, and compare the cellular area (CA); cytoplasmic area (Cyt A); nuclear area (NA); nuclear perimeter (NP); nuclear form factor (NF); and nuclear-cytoplasmic ratio (N/C) of the cells in different grades of OSCC. Materials and Methods: Fifty OSCC cases were obtained and stained with hematoxylin and eosin which were graded according to the WHO classification. The sections were subjected to morphometric analysis to analyze all the morphometric parameters in different grades of OSCC and subjected to one-way ANOVA statistical analysis. Results: CA and Cyt A decreased from normal mucosa with dedifferentiation of OSCC. The NA and NP increased in carcinoma group when compared to normal mucosa but decreased with dedifferentiation of OSCC ( P < 0.05). NF had no significance with normal mucosa and different grades of OSCC ( P > 0.05), while N/C ratio increased from normal mucosa through increasing grades of OSCC, reaching the highest value in poorly differentiated squamous cell carcinoma ( P < 0.05). Conclusion: Both cellular and nuclear variables provide a more accurate indication of tumor aggressiveness than any single parameter. Morphometric analysis can be a reliable tool to determine objectively the degree of malignancy at the invasive tumor front. [ABSTRACT FROM AUTHOR]

Aim: Studies reveal that invasive tumor front may be the best field for quantification of proliferative and apoptotic markers. The current study assessed the expression of Ki-67 antigen and p53 protein at invasive tumor front of oral squamous cell carcinoma (OSCC) and correlated the immunostaining with the histologic grades of malignancy. Materials and Methods: A total of 80 slides sample was prepared for the study, one each from ten normal oral mucosa cases and two each from 30 OSCC cases. The OSCC patients were biopsied along invasive tumor front, and samples were immunohistochemically analyzed for the expression of both Ki-67 antigen and p53 protein. Results: Of the total 30 OSCC cases, the expression of p53 was found positive in 20 cases (66.6%), while Ki-67 expression was found positive in 21 cases (70%). All the cases in the control group were negative. A higher p53 and Ki-67 expression were seen in OSCC group as compared to normal mucosa. On comparing the control group with various grades of OSCC a statistically significant result was obtained. Conclusion: Higher and statistically significant expression was noted for both p53 and Ki-67 antigen. The results emphasize the potential of Ki-67 and p53 as biomarkers of carcinogenesis in OSCC. Ki-67 expression was comparatively higher when compared with p53 except in poorly differentiated squamous cell carcinoma and signifies actively proliferating malignant cells at invasive tumor front.

Raf-1 kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, suppresses metastasis in a number of cancer types, including colorectal carcinoma (CRC); thus, RKIP downregulation significantly contributes to CRC invasiveness and metastatic potential. However, our previous study demonstrated that RKIP-positive tumors in CRC patients are predictive of hepatic colorectal metastases (HCMs). Based on the previous finding that the ERK pathway can be activated independently of RKIP, we hypothesized that RKIP-expressing HCMs may express significant levels of phosphorylated ERK (pERK). Thus, the present study evaluated the expression of RKIP and pERK in 68 HCM tissue samples using immunohistochemistry. RKIP expression was positive in 22 (32.4%) of the 68 samples, seven (31.8%) of which exhibited nuclear pERK immunoreactivity exclusively at the invasive tumor front. Furthermore, pERK expression at the invasive front was significantly associated with recurrent HCM following hepatic resection, and pERK expression observed at the invasive front of RKIP-expressing HCMs indicated that the activation of the ERK pathway may also be involved in the invasive process of these tumors, despite the presence of RKIP. A strong association between pERK expression and the presence of recurrent HCM may indicate that the ERK pathway is important in the metastatic recurrence of RKIP-positive HCM. [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]

Background: The invasive front is presumed to contain the most aggressive subpopulation of tumor cells that ultimately invade, spread locally and metastasize. Studying the histopathological grading of the tumor/ tissue interface at the invasive front may help in developing the treatment plan., Objectives: The aim of this study was to check the reliability of the tumor/tissue interface in predicting lymph node metastasis in oral squamous cell carcinoma (OSCC) of the tongue by evaluating the following: the histopathological grading of hematoxylin and eosin (H&E)-stained excision biopsy specimens according to the modified version of Broder's classification system; and the invasive tumor front (ITF) with the modified version of Bryne's grading system. The study also aimed at studying the lymph nodes for metastases and comparing these histopathological grading systems and lymph node metastases., Material and Methods: All retrospective and prospective cases from the archives of the Department of Oral Pathology and Microbiology of the A.B. Shetty Memorial Institute of Dental Sciences (ABSMIDS), NITTE University in Mangalore, India, collected during the period from 2012 to 2014 were considered for histopathological grading., Results: This study found a significant association between the modified version of Bryne's ITF grading system and lymph node metastases whereas the widely used modified version of Broder's classification failed to show any statistical significance. Only the multifactorial malignancy grading of the deep invasive margins of OSCC proved to be of high prognostic value., Conclusions: The study found that the degree of keratinization, nuclear polymorphism, the pattern of invasion, and the host response showed significant variation at the invasive front of the tumor as compared to superficial parts, which makes Bryne's grading system more reliable than Broder's grading system.

Extramural venous invasion (EMVI) is prognostic for colorectal cancer; however, veins are only detected partially by normal perpendicular preparation. Therefore, reported findings are conflicting and standardization is required. A total of 239 resection specimens were examined by tangential preparation of the extramural veins at the invasive tumor front. Average follow-up was 39 months. The relationship of EMVI to metachronous hematogenic metastasis (MHM) was evaluated. With this method, a high prevalence of EMVI beginning in stage II is apparent. In stage I, 66% of patients with EMVI developed MHM; in stage II, 25%; and in stage III, 49%. In stage III, the number of tumor-invaded veins is crucial. In the absence of detection of EMVI, MHM occurred in 1 of 29 patients in stage II and in 2 of 13 patients in early stage III. By tangential sectioning at the invasive tumor front, we found a high incidence of EMVI beginning in stage II, which increases with tumor stage. Especially in stages II and III, the correct determination of absent EMVI has a high negative predictive value for MHM. In stage I, EMVI defines a patient group with increased risk for MHM. The quantification of EMVI is an important issue for standardization., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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]