Role of stromal myofibroblasts in the progression of oral lesions from dysplasia to invasive carcinoma (original) (raw)

Evaluation of myofibroblasts in superficial and deep layers of oral squamous cell carcinoma; an immunohistochemical study

Immunopathologia Persa, 2019

Introduction: Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity with a high mortality rate. Myofibroblast in the stroma of malignant tumor is one of the main factors that accelerates and modulates tumor progression and invasiveness. Objectives: The current study aimed to investigate the presence of myofibroblasts in reactive oral lesion and OSCC and to compare its staining in superficial and deep layers in different histological grades. Patients and Methods: The study included the archival tissues of 30 OSCCs and 30 oral reactive lesions. The myofibroblast was assessed in superficial and deep layers by immunohistochemical study of alpha smooth muscle actin (α-SMA). Data were analyzed by SPSS software using chi-square, Kruskal-Wallis, and Mann-Whitney U tests. P < 0.017 was considered to be statistically significant. Results: The results revealed that presence of myofibroblasts was significantly higher in OSCCs compared to oral reactive lesions (P = 0.0001). The results also showed that myofibroblasts presented more in the deep layers than in the superficial layers of OSCC (P = 0.0001). A statistically significant difference was observed in myofibroblasts among different histological grades of oral squamous cell carcinoma (P = 0.0001). Conclusion: The findings highlight that the presence of myofibroblast in the stroma, assessed by α-SMA, indicates tumor progression and invasiveness in the patients with OSCC.

Expression of Myofibroblasts in Oral Squamous Cell Carcinoma: An Immunohistochemical Study

The journal of contemporary dental practice, 2016

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignancy affecting the orafacial region and with a high mortality rate. The fact that stroma of the tumor modulates and facilitates the progression and metastasis of the malignancy has been shown in the past studies. The cells of the activated stroma that are responsible for the progression and metastasis of the tumor are the fibroblasts having smooth muscle properties. These myofibroblasts are said to secrete numerous inflammatory mediators and factors which are said to play a crucial role in tumor progression. Therefore, we evaluated the presence of myofibroblasts in OSCC, by immunohisto-chemistry using alpha smooth muscle actin (a-SMA) antibody. We evaluated a total of 50 biopsy specimens from the archives of the oral pathology, where 20 specimens out of 50 were of well-differentiated OSCC (WDOSCC), 20 were of poorly differentiated OSCC (PDOSCC), and 10 were of normal healthy controls. All the specimens were...

Myofibroblasts and Tumor Micro-environment in Oral Squamous Cell Carcinomas – A Histochemical and Immunohistochemical Analysis

Texila International Journal of Public Health, 2024

Oral squamous cell carcinoma is a multi-factorial disease and no single causative factor has been primarily held responsible. Its pathogenesis is a multistep process involving initiation, promotion and tumor progression. The tumor micro-environment, particularly the collagen characteristics, and mesenchymal cells like myofibroblasts are increasingly implicated. The present study aims to determine the myofibroblast distribution and stromal characteristics in different grades of oral squamous cell carcinoma. Total of 46 specimens of different grades of oral squamous cell carcinoma were selected from departmental archives and subjected to immunohistochemical evaluation of myofibroblasts using α-smooth muscle actin marker. Parallel sections were subjected to van gieson staining to determine the characteristics of the collagen of the tumor stroma. Statistical analysis was performed for comparison between the different grades of oral squamous cell carcinoma. 80% of squamous cell carcinoma specimens were positive for α-smooth muscle actin. Poorly differentiated carcinoma specimens consistently demonstrated higher concentration of α-SMA positive myofibroblasts and a dense stroma. There was a positive correlation between myofibroblasts and the stromal density. The interesting feature was the higher concentration of myofibroblasts in the stroma away from the tumor islands the results indicate that the effect of the myofibroblasts on the tumor stroma may play a role in the fundamental cellular processes essential for tumor progression. It is well known that TGF-β dependent accumulation of collagen type 1 in tumor microenvironment is related to increased tumor invasiveness. Therefore, myofibroblasts may play a role in tumor growth and invasion.

Analysis of Expression of Myofibroblast in Oral Squamous Cell Carcinoma Cases: A Case-Control Study

Saudi Journal of Pathology and Microbiology, 2020

Background: In the past couple of decades, considerable importance has been given on the role of myofibroblasts (MFs) in tumour progression and prognosis. Myofibroblasts create a physical barrier between carcinoma cells and immune system of the: body against cancer. Hence; the present study was undertaken for assessing the expression of myofibroblast in oral squamous cell carcinoma cases and comparing it with healthy controls. Materials & Methods: A total of 20 biopsy specimens of oral squamous cell carcinoma and 20 healthy controls were enrolled in the present study. Complete demographic details and clinical data of all the specimens were obtained from data records. Two sections were obtained from each specimen: one for staining immune-histo-chemically using α-SMA antibody (alpha-smooth muscle actin antibody) and other for staining with haematoxylin and eosin. Criteria described by Etemad-Moghadam S et al were used for evaluating the expression of myofibroblast. Based on these criteria, staining index was graded as zero, moderate and high. Blood capillaries were taken as positive controls. Comparison was done in between the OSCC group and the control group. All the results were recorded in Microsoft excel sheet and were analysed by SPSS software. Results: In the OSCC group, 90 percent of the cases had high staining index of myofibroblast, while the remaining 10 percent of the cases had moderate staining index. In the control group, all the specimens showed negative staining index. While comparing statistically, it was observed that mean staining was significantly higher among OSCC group in comparison to the control group. Conclusion: Myofibroblast play a definitive role in the invasive behaviour of OSCC. Hence, it is suggested that myofibroblasts might be used as a stromal marker for observing the severity and progression of OSCC.

Quantitative Assessment of Myofibroblast in Severe Dysplasia, Microinvasion and Oral Squamous Cell Carcinoma: An Immunohistochemical Study

The Journal of Contemporary Dental Practice, 2013

Myofibroblast are essential for the integrity of human body by virtue of its role in wound healing and pathological organ remodeling. Myofibroblast is a universal cellular component in mammalian lesions, but not a typical component of normal untraumatized tissues. Therefore its presence in abundance in case of cancer is a matter of concern. Tumor microenvironment plays a pivotal role in tumor progression. These so called cancer associated fibroblast or myofibroblast are the major components and occur in stromal tissue during carcinogenesis processes. This study is a quantitative assessment of presence and distribution of myofibroblast in severe dysplasia, microinvasion and oral squamous cell carcinoma (OSCC).

Significance of myofibroblast appearance in squamous cell carcinoma of the oral cavity on the occurrence of occult regional metastases, distant metastases, and survival

International Journal of Oral and Maxillofacial Surgery, 2015

The aim of the present study was to assess the frequency of stromal myofibroblasts appearance, and to further clarify whether myofibroblasts influence tumor suppression or progression. Surgical resection specimens from 152 patients with cT1-T3N0 oral squamous cell carcinoma (OSCC) were analysed. Frequency of myofibroblasts within tumoral stroma was assessed immunohistochemically and compared with other clinically and histopathological factors. Immunohistochemical reaction for alpha-smooth muscle actin showed positive cells in stroma of 84.2% (n=128) of OSCC. Increased presence of myofibroblasts in the tumor stroma was significantly correlated with T stage (P = 0.019), presence of occult neck metastases (P < 0.001), regional recurrence (P = 0.037), and distant metastases (P = 0.008). There was also association between presence of myofibroblasts and patient's survival (P = 0.009). Presence of myofibroblasts was not associated with local recurrence, tumor cellular differentation, mode of invasion, and bone invasion. Results of this study suggest that myofibroblast proliferation facilitates tumour invasion, occurrence of occult neck disease and distant metastases. Survival rate was poorer in patients with abundant myofibroblasts. Further investigations on tumor-associated stroma at invasive front are needed in order to provide new diagnostic markers and therapeutic strategies.

An Immunohistochemical and Polarizing Microscopic Study of the Tumor Microenvironment in Varying Grades of Oral Squamous Cell Carcinoma

Journal of pathology and translational medicine, 2018

Invasion of epithelial cells into the connective tissue brings about massive morphological and architectural changes in the underlying stroma. Myofibroblasts reorganize the stroma to facilitate the movement of tumor cells leading to metastasis. The aim of this study was to determine the number and pattern of distribution of myofibroblasts and the qualitative and quantitative change that they cause in the collagen present in the stroma in various grades of oral squamous cell carcinoma (OSCC). The study was divided into two groups with group I (test group, 65 cases) consisting of 29 cases of well-differentiated squamous cell carcinoma, 25 moderately differentiated SCC, and 11 poorly differentiated SCC, and group II (control group) consisting of 11 cases of normal mucosa. Sections from each sample were stained with anti-α-smooth muscle actin (α-SMA) antibodies, hematoxylin and eosin, and Picrosirius red. Several additional sections from each grade of OSCC were stained with Masson's...

Isolation and characterization of myofibroblast cell lines from oral squamous cell carcinoma

Oncology Reports, 2011

Oral squamous cell carcinoma (OSCC) invasion is followed by several stromal events such as inflammatory and immune cell infiltration, neo-vascularization, fibroblast activation and occasionally myofibroblast emergence. Our previous studies demonstrated that myofibroblasts in the stroma of OSCC are associated with a more aggressive behavior, leading to shorter patient overall survival. Therefore, we evaluated whether OSCC-associated myofibroblasts have different characteristics compared to OSCC-associated fibroblasts. OSCC myofibroblast cell lines were isolated, cultured and characterized on the basis of the expression of specific isoform · of smooth muscle actin (·-SMA) and of the excessive production of type I collagen. To assess the proliferative potential of the cell lines, growth curves were constructed, whereas the production and activity of matrix metalloproteinases (MMP) were analyzed by ELISA and enzymography, respectively. Myofibroblast clones were positive for ·-SMA and vimentin, and negative for pan-cytokeratin and CD34. In long time cultures, Western blotting, flow cytometry and ELISA analysis revealed constant ·-SMA expression and elevated production of type I collagen. There were no differences on proliferative potential between fibroblast and myofibroblast clones, but myofibroblast cells secreted significantly higher levels of MMP-1, -2, -9 and -13. Furthermore, MMP-2 gelatinolytic activity was significantly higher in myofibroblast clones. The results of this study suggest that myofibroblasts may contribute to OSCC invasion through elevation of MMP synthesis.

Evaluation of myofibroblasts in oral squamous cell carcinoma using H1 calponin: An immunohistochemical study

Journal of oral and maxillofacial pathology : JOMFP

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. The purpose of this study was to evaluate and compare the presence of myofibroblasts in normal mucosa, early invasive carcinoma and different grades of OSCC. The study included the archival tissues of 18 OSCC of well, moderate and poorly differentiated grades, three early invasive carcinomas and five normal mucosa. Myofibroblasts were identified by immunohistochemical detection of h1 calponin. The percentage and intensity of h1 calponin were examined and positive immunostaining was observed in the myofibroblasts of all SCCs and early invasive carcinomas; however, these cells did not stain in the normal epithelium specimens. The presence of myofibroblasts was significantly higher in invasive pattern of OSCCs compared to normal mucosa cases (P < 0.070). A significa...

Comparative evaluation of the frequency of myofibroblasts between oral and cutaneous squamous cell carcinomas

Caspian Journal of Dental Research, 2016

Introduction: Differentiation of fibroblasts to myofibroblasts is an initial and very important event in tumor genesis. Myofibroblasts produce proteinases that stimulate invasion in cancers. Due to the more malignant potential of oral squamous cell carcinoma (OSCC) compared to cutaneous squamous cell carcinoma (CSCC) , the aim of the present study was to compare myofibroblasts between OSCC and CSCC to understand whether myofibroblasts can help more malignant potential of OSCC compared to CSCC or not. Materials &Methods: This cross-sectional study included 40 cases of OSCC and CSCC and 20 cases of normal skin and normal oral mucosa. Then, 4-micron sections of paraffin-embedded tissue blocks of studied groups were stained immunohistochemically with α-SMA antibody. Mean percentage of myofibroblasts was calculated in invasive fronts of OSCCs with CSCCs and also in normal samples and staining intensity of cells for α-SMA marker and distribution pattern of myofibroblasts were determined. Results: The differences of average percentage of myofibroblasts in OSCC and CSCC compared to normal groups were significant (Pvalue=0.007and Pvalue=0.003 respectively), but when we compared OSCCs and CSCCs, the difference was not significant. Also, there were no significant differences between OSCC and CSCC with regard to staining intensity and pattern. Conclusion: Different biologic behavior of OSCC compared to CSCC doesn’t depend on myofibroblasts and other factors can be involved.