Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Relationship between lip skin biophysical and biochemical characteristics with corneocyte unevenness ratio as a new parameter to assess the severity of lip scaling.

OBJECTIVE: Lip skin dryness and chapping are major concerns related to lip skin care in many populations. The distinctive features of lip skin, such as the low water-holding capacity and weak skin barrier, are strongly associated with these problems; however, few studies have examined lip skin characteristics and the mechanisms underlying these issues. This study was conducted to identify the biophysical properties of dry lip skin and molecular targets affecting lip skin physiology. METHODS: Skin hydration, transepidermal water loss and lip skin scaling were evaluated in 40 female subjects. Skin scaling was assessed as a percentage area divided into five categories (G0, G1, G2, G3 and G4) according to the thickness level of tape-stripped corneocytes. The activities and amounts of proteases, cathepsin D and bleomycin hydrolase were measured as markers for the desquamation process and skin hydration, respectively. RESULTS: Skin hydration showed a significantly positive correlation with the percentage area of evenly thin corneocytes (G0) and negative correlations with the percentage areas of slightly thick to severely thick corneocytes (G1-G4). The corneocyte unevenness ratio (CUR) was calculated by dividing the sum of the G1, G2, G3 and G4 values with the G0 value. The CUR was significantly negatively correlated with skin hydration, suggesting that CUR is a new parameter representing the severity of lip scaling. Subjects with lower hydration and higher CUR had higher bleomycin hydrolase activity and lower cathepsin D activity, respectively, than subjects with higher hydration and lower CUR. CONCLUSION: Our study revealed a correlation between lip skin hydration and severity of lip scaling and verified the association of protease activity with the hydration and chapping state of lip skin. These observations provide a basis for further studies of the persistent problem of lip skin dryness and chapping.

OBJECTIF: La sécheresse et la gerçure de la peau des lèvres sont des préoccupations majeures liées aux soins de la peau des lèvres chez de nombreuses populations. Les caractéristiques distinctives de la peau des lèvres, telles que la faible capacité de rétention d'eau et la faible barrière cutanée, sont fortement associées à ces problèmes ; cependant, peu d'études ont examiné les caractéristiques de la peau des lèvres et les mécanismes sous-jacents à ces problèmes. Cette étude a été menée dans le but d'identifier les propriétés biophysiques de la peau sèche des lèvres et les cibles moléculaires affectant la physiologie de la peau des lèvres. MÉTHODES: L'hydratation cutanée, la perte d'eau transépidermique et la desquamation de la peau des lèvres ont été évaluées chez 40 sujets de sexe féminin. La desquamation cutanée a été évaluée en tant que pourcentage de surface, divisée en cinq catégories (G0, G1, G2, G3 et G4) en fonction du niveau d'épaisseur des cornocytes sur la bande adhésive. Les activités et quantités des protéases, de la cathepsine D et de la bléomycine hydrolase ont été mesurées comme marqueurs du processus de desquamation et de l'hydratation cutanée, respectivement. RÉSULTATS: L'hydratation cutanée a montré une corrélation significativement positive avec le pourcentage de surface avec cornocytes uniformément minces (G0), et des corrélations négatives avec les pourcentages de surface avec cornocytes légèrement épais à très épais (G1-G4). Le rapport d'irrégularité des cornocytes (Corneocyte Unevenness Ratio, CUR) a été calculé en divisant la somme des valeurs de G1, G2, G3 et G4 par la valeur de G0. Le CUR était significativement corrélé négativement avec l'hydratation de la peau, ce qui suggère que le CUR est un nouveau paramètre représentant la gravité de la desquamation des lèvres. Les sujets avec une hydratation plus faible et un CUR plus élevé présentaient une activité de la bléomycine hydrolase plus élevée et une activité de la cathepsine D plus faible, respectivement, par rapport aux sujets avec une hydratation plus élevée et un CUR plus faible. CONCLUSION: Notre étude a révélé une corrélation entre l'hydratation de la peau des lèvres et la gravité de la desquamation des lèvres, et a vérifié l'association de l'activité de la protéase avec l'état d'hydratation et de gerçure de la peau des lèvres. Ces observations fournissent une base pour d'autres études sur le problème persistant de la sécheresse et de la gerçure de la peau des lèvres.

Actinic cheilitis: Morphometric parameters and its relationship with the degree of epithelial dysplasia.

Actinic cheilitis (AC) is a potentially malignant lesion caused by chronic sun exposure. This study aimed to evaluate the relationship between the degree of epithelial dysplasia and morphometric findings in AC. Sixty-eight slides of AC cases were selected and classified according to the grade of epithelial dysplasia, following morphologic criteria of World Health Organization. For morphometric analysis, the slides were scanned and images were analyzed using Pannoramic Viewer software. We obtained vertical measurements of the parameters: thicknesses of the keratin layer, lamina propria and zone of solar elastosis in three selected fields. Thirty-seven (54.4%) of the analyzed cases were classified as none/mild dysplasia and 31 (45.6%) as moderate/severe epithelial dysplasia. Cases with a moderate/severe dysplasia exhibited a thicker layer of keratin (median = 0.055 mm) than none/mild dysplasia (median = 0.045 mm) (p = 0.033). No significant differences in the thicknesses of lamina propria and zone of solar elastosis were observed according to the grade of epithelial dysplasia. A positive significant correlation between keratin layer and lamina propria thicknesses was found (p = 0.019). Based on our findings, rigorous clinical follow-up should be recommended for patients whose histopathological examination shows a greater thickness of the keratin layer.

Expression of stem cell markers Nanog and Nestin in lip squamous cell carcinoma and actinic cheilitis.

Cancer stem cell (CSC) proteins have been observed in several lesions and are associated with tumor beginning, evolution, and resistance to treatment. OBJECTIVES: To investigate the presence of NANOG, NESTIN, and ß-tubulin in lip squamous cell carcinoma (LSCC), actinic cheilitis (AC), and normal epithelium (NE). MATERIALS AND METHODS: Thirty cases of LSCC, thirty cases of AC (both analyzed according to the WHO classification and AC according to the binary classification), and twenty cases of NE were submitted to an immunohistochemical study. RESULTS: NANOG was more expressed in the nuclei of AC compared to NE (p = 0.007), as well as in high-risk AC cases (p = 0.017) and well-differentiated LSCCs (no significance). There was an accumulation of nuclear NANOG from mild to moderate and severe ACs. NESTIN was significantly less present in NE compared to AC (p = 0.001) and LSCC (p = 0.003). There was a higher expression in severe dysplasia or high-risk AC and well-differentiated LSCC. These results indicate an upregulation of NANOG and NESTIN in the early stages of carcinogenesis. ß-tubulin was intensely present in all lesions. CONCLUSION: The results suggest an upregulation of NANOG and NESTIN in the biological behavior these diseases, mainly in the transformation from AC to LSCC.

Expression of cancer stem cell markers CD44, ALDH1 and p75NTR in actinic cheilitis and lip cancer.

PURPOSE: The aim of this work was to evaluate the expression of the cancer stem cell (CSC) markers CD44, ALDH1 and p75NTR in the ultraviolet-induced lesions actinic cheilitis (AC) and lip squamous cell carcinoma (LSCC), and to correlate it with p53 expression. METHODS: Immunohistochemistry was performed in 4 cases of normal lip (NL), 43 of AC and 20 of LSCC. RESULTS: All cases were positive for CD44, showing a membranous staining without differences between the groups. ALDH1 showed cytoplasmic staining and it was invariable amongst the grades of epithelial dysplasia and between AC and LSCC. p75NTR presented membranous/cytoplasmic staining in the basal and parabasal layer of NL and AC, while LSCC presented cytoplasmic staining in the peripheral layers of the tumor islands. p75NTR showed different expression amongst the dysplasia grades (p < 0.001) but no differences between AC and LSCC. p53 expression was similar amongst the dysplasia grades and between AC and LSCC. CD44, ALDH1 and p75NTR were unrelated amongst themselves and to p53 expression. CONCLUSIONS: CSC markers are expressed in potentially malignant and malignant lesions of the lip. Their expressions were invariable between AC and LSCC and unrelated to p53. p75NTR expression increased with the worsening of epithelial dysplasia grade.

Thioredoxin and metallothionein: Homeostasis-related proteins in lip carcinogenesis.

OBJECTIVE: Thioredoxin (Trx) and metallothionein (MT) are involved in the development of some carcinomas; however, the role of these proteins in labial carcinogenesis has not yet been tested. The aims of the study were to evaluate and to correlate the immunoexpression of Trx and MT in actinic cheilitis, lip squamous cell carcinoma, and normal vermillion lip mucosa. DESIGN: Immunohistochemistry was undertaken for Trx and MT in samples of actinic cheilitis, lip squamous cell carcinoma, and normal lip mucosa. Qualitative and semi-quantitative evaluations were conducted. The proportion of stained cells, intensity of staining, and the cell compartment labeled were evaluated. A quickscore index was also calculated by multiplying the values of extension and intensity of nuclear and cytoplasmic staining, respectively, giving a maximum value of 9. Statistics were performed. RESULTS: A remarkable nuclear Trx staining was seen in normal lip mucosa and cheilitis, not in carcinoma (p<0.05). Cytoplasmic Trx expression was widely detected in all lesions (p>0.05). MT was broadly expressed in nuclei and cytoplasm of carcinoma, but not in normal lip mucosa and cheilitis (p<0.05). Quickscores were in accordance with the qualitative results. CONCLUSIONS: The current study showed a different immunopattern of Trx and MT between normal lip mucosa, actinic cheilitis and lip squamous cell carcinoma. The cellular compartment-based analyses evidenced differences that can be related to the proteins function. Considering the relevant roles of these proteins in cellular homeostasis, they seem to have an important role in lip carcinogenesis.

Evaluation of the efficacy of photodynamic therapy for the treatment of actinic cheilitis.

INTRODUCTION: Actinic cheilitis (AC) is a lip intraepithelial neoplasia, whose cells present alterations similar to those presented by invasive squamous cell carcinomas (SCCs). OBJECTIVE: To conduct clinical and laboratory evaluation by histopathology and immunohistochemistry of the efficacy of actinic cheilitis treatment using photodynamic therapy (PDT) with methyl aminolevulinate (MAL) and noncoherent red light. MATERIALS AND METHODS: Patients with actinic cheilitis detected by histopathological examination were submitted to two sessions of photodynamic therapy with a two-week interval between them. They were examined immediately after the sessions, four, six, and twelve weeks after beginning treatment when a new biopsy was carried out. Clinical histopathological and immunohistochemical parameters were evaluated before and after treatment. RESULTS: Of the 23 patients who underwent biopsy, 16 completed two photodynamic therapy sessions and the material of one patient was insufficient for immunohistochemistry. Complete clinical response was achieved in 62.5% (10 of 16 patients) and 37.5% still remained with clinical evidence of AC. In spite of this, no case of cure by histopathological analysis was found. There was no significant statistical change among the values of Ki-67, survivin, and p53 observed before and after treatment. CONCLUSION: Photodynamic therapy, as carried out in this trial, was not an efficacious therapeutic option for treating patients with actinic cheilitis included in this sample.

Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis.

BACKGROUND: The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. OBJECTIVE: To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. METHODS: We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. RESULTS: Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. CONCLUSION: This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis.

Optical diagnosis of actinic cheilitis by infrared spectroscopy.

Actinic cheilitis (AC) is considered a potentially malignant disorder of the lip. Biomolecular markers study is important to understand malignant transformation into squamous cell carcinoma. Fourier transform infra red (FT-IR) spectroscopy was used to analyze AC in this study. OBJECTIVES: The aim of the study was to evaluate if FT-IR spectral regions of nucleic acids and collagen can help in early diagnosis of malignant transformation. METHODS: Tissues biopsies of 14 patients diagnosed with AC and 14 normal tissues were obtained. FT-IR spectra were measured at five different points resulting in 70 spectra of each. Analysis of Principal components analysis (PCA) and linear discrimination analysis (LDA) model were also used. In order to verify the statistical difference in the spectra, Mann-Whitney U test was performed in each variable (wavenumber) with p-value <0.05. RESULTS: After the Mann-Whitney U test the vibrational modes of CO (Collagen 1), PO2 (Nucleic Acids) and CO asymmetric (Triglycerides/Lipids) were observed as a possible spectral biomarker. These bands were chosen because they represent the vibrational modes related to collagen and DNA, which are supposed to be changed in AC samples. Based on the PCA-LDA results, the predictive model corresponding to the area under the curve was 0.91 for the fingerprint region and 0.83 for the high wavenumber region, showing the greater accuracy of the test. CONCLUSIONS: FT-IR changes in collagen and nucleic acids could be used as molecular biomarkers for malignant transformation.

Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis

Abstract: Background: The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. Objective: To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. Methods: We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Results: Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. Conclusion: This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis.

Evaluation of hypoxia, angiogenesis, and lymphangiogenesis in actinic cheilitis.

BACKGROUND: Actinic cheilitis is a potentially malignant condition caused mainly by chronic sun exposure. Here we aim to evaluate the role of hypoxia, angiogenesis, and lymphatic density in the clinical and morphological progression of a series of cases of actinic cheilitis. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate positivity to hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF)-C, and D2-40 in 40 cases of actinic cheilitis of the lower lip. RESULTS: The cases studied exhibited variable degrees of positivity to the markers. The median number of lymphatic vessels was 3.2, 2.4, and 3.0 in lesions showing no epithelial dysplasia (NED) and with mild (MED) and moderate (MOED) epithelial dysplasia, respectively. The median VEGF-C positivity index was 82.44% (NED), 92.74% (MED), and 82.83% (MOED), and the median HIF-1α positivity index was 11.57% (NED), 5.26% (MED), and 13.55% (MOED). No significant differences in lymphatic density or median VEGF-C and HIF-1α positivity indices were observed between histological grades or clinical presentations of actinic cheilitis (P > 0.05). CONCLUSIONS: Although representing early events in lip carcinogenesis, the present results suggest that hypoxia, angiogenesis, and lymphangiogenesis do not influence the morphological or clinical progression of actinic cheilitis.

Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer.

This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p > 0.05). Immunoexpression of p53 was higher in SCC than in AC (p < 0.001), while p21 expression was more observed in AC when compared to SCC group (p = 0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r = -0.30, p = 0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process.

Relevance of HLA-G, HLA-E and IL-10 expression in lip carcinogenesis.

HLA-G, HLA-E and IL-10 are molecules which can provide tumor immunosuppression as well as the capacity of evasion to the immune system host. This study set out to evaluate HLA-G, HLA-E and IL-10 expression in lip squamous cell carcinoma (LSCC) and in a potentially malignant disorder (actinic cheilitis - AC), correlating the expression of these proteins with the degree of epithelial dysplasia. Immunohistochemistry was undertaken to identify HLA-G, HLA-E and IL-10 in samples from patients with LSCC (n=20), AC (n=30) and healthy lip mucosa (control) (n=10). A semiquantitative scoring system was used for analysis. Differences between the groups were evaluated using the Pearson Chi-Squared test. The percentage of LSCC samples showing high immunoreactivity (IRS>2) for HLA-G, HLA-E and IL-10 (neoplastic/epithelial cells) and HLA-E (stroma/connective tissue) was significantly higher that of the control (P<0.05). A tendency for a progressive increase in the proteins analyzed was observed from the control to AC and to LSCC. The degree of dysplasia in the AC samples was not significantly associated with the proteins evaluated (P>0.05). The high expression of HLA-G, HLA-E and IL-10 in AC and LSCC reflects the capacity that these pathologies have for evasion and progression.

Loss of cytokeratin 10 indicates malignant transformation in actinic cheilitis.

OBJECTIVES: The aim of this study was to investigate the relationship the expression of cytokeratins (CK10 and CK13) and the cell proliferation index determined by Ki-67 of lip squamous cell carcinoma and actinic cheilitis with different degrees of dysplasia. MATERIALS AND METHODS: Forty-five paraffin-embedded actinic cheilitis with and without dysplasia and 20 lip squamous cell carcinoma were analyzed by immunohistochemistry using anti-human anti-CK10, anti-CK13, and anti-Ki-67 antibodies. RESULTS: The majority of actinic cheilitis showed immunopositivity for CK10 and CK13 with decrease or loss of expression in dysplastic areas. In lip squamous cell carcinoma of the lip, heterogeneous expression of CK13 and immunonegativity for CK10 were observed. There was a statistically significant difference between CK10 expression in lip squamous cell carcinoma and in actinic cheilitis with or without dysplasia (p < 0.001). The cell proliferation index was higher in actinic cheilitis with dysplasia and lip squamous cell carcinoma than in actinic cheilitis without epithelial dysplasia. A significant correlation was found between the intensity of the epithelial dysplasia and the cell proliferation index (p < 0.001). CONCLUSION: These results provide evidence that there is a downregulation of CK10 expression in dysplastic areas of patients with actinic cheilitis and in those with lip squamous cell carcinoma (LSCC) and that the index of cell proliferation, determined by Ki-67, is directly correlated with the intensity of the epithelial dysplasia. CLINICAL RELEVANCE: Altogether, these results suggest that CK10 expression and the epithelial cell proliferation index can help to identify malignant transformation in the lip region.

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

BACKGROUND: There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. METHODS: Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). RESULTS: The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). CONCLUSION: There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm.

Pattern of galectins expression in actinic cheilitis with different risks of malignant transformation.

BACKGROUND: Actinic cheilitis (AC) is a chronic inflammatory lesion that in some situations can turn into squamous cell carcinoma of the lip. The molecular mechanisms involved in this process are not yet completely understood. This study aimed to investigate the expression pattern of galectins in actinic cheilitis according to the histopathological grading. METHODS: Immunoexpression of galectin-1, galectin-3, galectin-7, and galectin-9 was semiquantitatively analyzed in 65 cases of actinic cheilitis graded as low risk (n = 40) or high risk (n = 25) of malignant transformation. Association between the location of the galectins in the cellular compartments and histopathological grading was analyzed. RESULTS: Galectin-1 was mainly observed in the cell cytoplasm, and was elevated (score 3) in 60% of cases, regardless of the histopathological grade (P > 0.05). Galectin-3 expression was higher in high-risk group than in the low-risk group (P < 0.05), with a predominant expression in the cytoplasm and nucleus of low-risk (67.5%), and only in the cytoplasm of high-risk cases (60%) (P < 0.05). Galectin-7 expression did not show significant differences between low-risk and high-risk groups (P > 0.05). With respect to galectin-9, 89.2% of cases were positive, showing decrease in median of scores as there was an increase in histological grade (P < 0.001), with predominant expression in the nucleus and cytoplasm. CONCLUSIONS: This study is the first indication of galectins involvement in the pathogenesis and morphologic progression of actinic cheilitis, particularly galectin-3 and galectin-9.

Immunohistochemical expression of matrix metalloproteinase-1, matrix metalloproteinase-2 and matrix metalloproteinase-9, myofibroblasts and Ki-67 in actinic cheilitis and lip squamous cell carcinoma.

Matrix metalloproteinases (MMPs), myofibroblasts (MFs) and epithelial proliferation have key roles in neoplastic progression. In this study immunoexpression of MMP-1, MMP-2 and MMP-9, presence of MFs and the epithelial proliferation index were investigated in actinic cheilitis (AC), lip squamous cell carcinoma (LSCC) and mucocele (MUC). Thirty cases of AC, thirty cases of LSCC and twenty cases of MUC were selected for immunohistochemical investigation of the proteins MMP-1, MMP-2, MMP-9, α-smooth muscle actin (α-SMA) and Ki-67. The MMP-1 expression in the epithelial component was higher in the AC than the MUC and LSCC. In the connective tissue, the expression was higher in the LSCC. MMP-2 showed lower epithelial and stromal immunostaining in the LSCC when compared to the AC and MUC. The epithelial staining for MMP-9 was higher in the AC when compared to the LSCC. However, in the connective tissue, the expression was lower in the AC compared to other lesions. The cell proliferation rate was increased in proportion to the severity of dysplasia in the AC, while in the LSCC it was higher in well-differentiated lesions compared to moderately differentiated. There were no statistically significant differences in number of MFs present in the lesions studied. The results suggest that MMPs could affect the biological behaviour of ACs and LSCCs inasmuch as they could participate in the development and progression from premalignant lesions to malignant lesions.

STAG2 expression in oral cancer and potentially malignant lesions.

Oral cancer is a world health problem, and one of the highest incidence rates of oral cancer worldwide occurs in Brazil. STAG2 is part of the cohesin complex which is responsible for sister chromatid cohesion. STAG2 loss of expression was reported in a range of tumors, and STAG2 loss was found to cause chromosomal instability and aneuploidy in cancer cells. On the basis of these findings, we investigated STAG2 expression in oral cancer and potentially malignant lesions. We investigated STAG2 immunoexpression in oral cancer, lip cancer, oral leukoplakia, and actinic cheilitis, including complete clinical information. Normal oral mucosa samples were included as normal controls. STAG2 protein was highly expressed in all samples. We further tested STAG2 expression in gastric adenocarcinomas and glioblastomas, as these tumor types were previously shown to lose STAG2 expression. We found homogenous expression of STAG2 by these tumor cells. Our results suggest that STAG2 loss of expression is not a common event in oral carcinogenesis.