RESUMEN
The association of syringocystadenoma papilliferum (SCAP) with verrucous carcinoma (VC) of the skin in the same lesion is a rare, but well-documented event. Although human papillomaviruses (HPV) have been proposed to have an etiologic role in the development of the verrucous proliferations associated with SCAP, most of the immunohistochemical and molecular studies have failed to show the presence of their genomic material in these lesions. We report a series of four cases of SCAP associated with VC in anogenital lesions. In two of the cases, we demonstrated the presence of the BRAF V600E mutation by polymerase chain reaction and immunohistochemistry, both in the glandular and in the squamous component. No HPV-related histopathologic changes were found, nor could the presence of viral DNA be showed.
Asunto(s)
Carcinoma Verrugoso , Mutación Missense , Neoplasias Primarias Secundarias , Proteínas Proto-Oncogénicas B-raf , Neoplasias de las Glándulas Sudoríparas , Adenomas Tubulares de las Glándulas Sudoríparas , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Carcinoma Verrugoso/genética , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/patología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/genética , Neoplasias Primarias Secundarias/metabolismo , Neoplasias Primarias Secundarias/patología , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Neoplasias de las Glándulas Sudoríparas/genética , Neoplasias de las Glándulas Sudoríparas/metabolismo , Neoplasias de las Glándulas Sudoríparas/patología , Adenomas Tubulares de las Glándulas Sudoríparas/genética , Adenomas Tubulares de las Glándulas Sudoríparas/metabolismo , Adenomas Tubulares de las Glándulas Sudoríparas/patologíaRESUMEN
BACKGROUND: Mcm-2 is a biomarker belonging to Mcm family of proteins which has rarely been used in oral potentially malignant and malignant lesions of the verrucous type. The objective of this study is to assess the expression of Mcm-2 in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC) and Oral Squamous Cell Carcinoma (OSCC) and compare it with the clinicopathological characteristics. METHODOLOGY: A total of 70 formalin fixed paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by using the SPSS software. RESULTS: There was a significant difference in Mcm-2 expression with quantitative analysis among all the groups (pâ¯<â¯0.05). There was a significant progressive increase in nuclear Labelling Indices (nLI) from NM (49.08%), VC (60.45%), VH with Dysplasia (64.10%), and OSCC (89.22%). CONCLUSION: The findings suggest that Mcm-2 may be a sensitive proliferation marker in oral potentially malignant and malignant lesions which may be useful for differentiating between VH with/ without dysplasia, VC and OSCC.
Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Carcinoma Verrugoso/diagnóstico , Carcinoma Verrugoso/metabolismo , Hiperplasia/diagnóstico , Componente 2 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Neoplasias de la Boca/diagnóstico , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/patología , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Adhesión en Parafina , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The Akt/mTOR pathway is activated in many malignancies, including oral squamous cell carcinoma (OSCC). However, the role of the Akt/mTOR pathway in oral verrucous carcinoma (OVC), a low-grade variant of OSCC, remains unknown. Thus, the objective of this study was to investigate the activation level of important markers of the Akt/mTOR pathway in OVC and to compare the results with OSCC samples. METHODS: The expression of p-Akt (Thr308), p-Akt (Ser473), and p-RPS6 was evaluated by immunohistochemistry in 30 OSCC cases, 18 OVC cases, and 30 control cases (normal epithelium overlying fibromas). Statistical analysis was performed to determine the differences in protein expression between samples. RESULTS: All OVC cases were positive for p-Akt (Thr308), p-Akt (Ser473), and p-RPS6. There were significant differences in expression level of all studied proteins between OVC and control, as well as between OVC and OSCC. However, OVC showed significant lower staining scores than OSCC. CONCLUSIONS: Our findings demonstrate that the Akt/mTOR pathway is upregulated in OVC, indicating a role for this pathway in the development and progression of this malignancy.
Asunto(s)
Carcinoma Verrugoso/enzimología , Neoplasias de la Boca/enzimología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/patología , Femenino , Fibroma/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Proteína S6 Ribosómica/metabolismo , Regulación hacia ArribaRESUMEN
Alterations in cell membrane glycosylation play important role in oral carcinogenesis. The present study evaluated salivary sialylation changes i.e. total sialic acid (TSA), sialidase activity, linkage specific (α2-3 and α2-6) sialoproteins and sialyl transferase (ST) activity in controls, patients with oral precancerous conditions (OPC) and oral cancer. Subjects enrolled included 100 controls, 50 patients with OPC, 100 oral cancer patients, and 30 post treatment follow-ups. TSA was estimated by spectrophotometric method, sialidase activity by spectrofluorometric assay and linkage specific biotinylated lectins (α2-3: sambucus nigra agglutinin and α2-6: maackia amurensis agglutinin) were used to detect α-2,3 and α-2,6 STs and sialoproteins by ELISA and dot blot respectively. An increasing trend of salivary TSA/TP ratio, sialidase activity, α2-3 sialoproteins, α-2,3 and α-2,6 ST activities was observed from controls to patients with OPC to oral cancer patients and levels were significantly elevated in oral cancer patients as compared to the controls. Sialidase activity exhibited significant association with metastasis and infiltration. Sialidase activity, TSA/TP ratio, α-2,3 and α-2,6 ST activities were found to be higher in patients with metastasis as compared to patients without metastasis. A progressive increase in TSA/TP ratio, sialidase activity, α2-3 and α2-6 sialoproteins was observed from controls to early to advanced stage of the disease. Sialidase activity, α2-3 and α2-6 sialoproteins and ST activities were found to be decreased in complete responders; while levels were elevated in non-responders. The results documented utility of salivary sialylation endpoints, a non invasive tool in monitoring of oral carcinogenesis.
Asunto(s)
Carcinogénesis/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrugoso/metabolismo , Leucoplasia Bucal/metabolismo , Neoplasias de la Boca/metabolismo , Fibrosis de la Submucosa Bucal/metabolismo , Lesiones Precancerosas/metabolismo , Adolescente , Adulto , Anciano , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/diagnóstico , Carcinoma Verrugoso/genética , Carcinoma Verrugoso/patología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , Leucoplasia Bucal/diagnóstico , Leucoplasia Bucal/genética , Leucoplasia Bucal/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Ácido N-Acetilneuramínico/metabolismo , Neuraminidasa/genética , Neuraminidasa/metabolismo , Fibrosis de la Submucosa Bucal/diagnóstico , Fibrosis de la Submucosa Bucal/genética , Fibrosis de la Submucosa Bucal/patología , Lectinas de Plantas/química , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Sialiltransferasas/genética , Sialiltransferasas/metabolismoRESUMEN
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a serious health disease that can lead to a reduced quality of life or even death. It ranks sixth in terms of cancer expansion. It is one of India's primary causes of natural death. In OSCC such potentially malignant Disorders (PMDs) are precancerous lesions with such a high risk of progression. Tumor angiogenesis is a one of the basic biomarkers that may influence the proliferation of a precancerous lesion into the cancerous lesion. Tropomyosin receptor kinase B (TrkB), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) also play important roles in carcinogenesis by promoting angiogenesis. The construction of new vessels of blood from existing vasculature is referred as angiogenesis. AIM OF THE STUDY: To get deep insights of immunohistochemistry expression of VEGF, BDNF, and TRKB in oral epithelial dysplasia (OED), verrucous carcinoma (VC), and OSCC. MATERIAL AND METHODS: The study included 100 formalin-fixed paraffin-embedded tissue blocks from 20 cases of OED, 20 cases of VC, and 60 cases of OSCC [20 cases of well-differentiated oral squamous cell carcinoma (WD-OSCC), 20 cases of moderately differentiated oral squamous cell carcinoma (MD-OSCC), and 20 cases of poorly differentiated oral squamous cell carcinoma (PD-OSCC). The staining intensity and distribution of VEGF, BNDF, and TrkB were examined and statistically analyzed using analysis of variance (ANOVA), post hoc Bonferroni test, independent t-test, Pearson's Chi-square test, and Pearson's correlation coefficient test. RESULTS: The immunoexpression of VEGF, BDNF, and TrkB was found to be elevated in the order of OEDs, VC, and OSCC. The percentage of positive was highest in PD-OSCC, followed by MD-OSCC and WD-OSCC. CONCLUSION: Based on our findings, angiogenesis plays a significant role in tumor growth and metastasis. A substantial relationship was discovered between VEGF, BDNF, TrkB expression, and increases in vascularity throughout the transition from OEDs to VCs and OSCCs.
Asunto(s)
Biomarcadores de Tumor , Factor Neurotrófico Derivado del Encéfalo , Carcinoma de Células Escamosas , Carcinoma Verrugoso , Neoplasias de la Boca , Receptor trkB , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Pronóstico , Masculino , Carcinoma Verrugoso/patología , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/diagnóstico , Receptor trkB/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Femenino , Persona de Mediana Edad , Adulto , Anciano , Lesiones Precancerosas/patología , Lesiones Precancerosas/metabolismo , Glicoproteínas de Membrana/metabolismo , Inmunohistoquímica , Neovascularización Patológica/patología , Neovascularización Patológica/metabolismo , Mucosa Bucal/patología , Mucosa Bucal/metabolismoRESUMEN
AIMS: To assess the DNA content of cases of oral proliferative verrucous leukoplakia (PVL) and correlate the DNA ploidy findings with the expression of Mcm2, geminin, and Ki67, and with clinicopathological data. METHODS AND RESULTS: DNA quantification was performed by image cytometry using the ACIS III Automated Cellular Imaging System. Expression of Ki67, Mcm2 and geminin was determined by immunohistochemistry. There were 21 cases of PVL, the female/male ratio was 6:1, and the average age was 65.5 years. Seventeen patients (81.0%) did not report tobacco and alcohol consumption. Nine patients (42.9%) developed verrucous or squamous cell carcinoma. Levels of Mcm2 expression showed a positive correlation with increasingly severe epithelial changes (P = 0.03). Twenty patients had their DNA examined by ACIS III, and 19 (95%) showed aneuploidy. The frequency and severity of aneuploidy (P < 0.0001), the mean values of the DNA heterogeneity index (P < 0.0001) and the 5n-exceeding fractions (P = 0.0007) increased according to epithelial alterations. Abnormal DNA content was observed even in the more indolent lesions. CONCLUSIONS: Mcm2 expression and DNA ploidy analysis could be used to predict areas of malignant transformation. The clinicopathological findings associated with the immunohistochemical and DNA ploidy results support the distinct and aggressive profile of this entity.
Asunto(s)
Aneuploidia , Carcinoma Verrugoso/patología , Proteínas de Ciclo Celular/metabolismo , Leucoplasia Bucal/patología , Neoplasias de la Boca/patología , Proteínas Nucleares/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Verrugoso/genética , Carcinoma Verrugoso/metabolismo , Proliferación Celular , Transformación Celular Neoplásica , ADN de Neoplasias/genética , Femenino , Geminina , Humanos , Citometría de Imagen , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Leucoplasia Bucal/genética , Leucoplasia Bucal/metabolismo , Masculino , Persona de Mediana Edad , Componente 2 del Complejo de Mantenimiento de Minicromosoma , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: Nuclear localization of cyclin B1 is an indicator for cells undergoing mitotic division, and the overexpression has shown promising results as a good prognostic predictor for patients of squamous cell carcinoma (SCC). Cyclin B1 overexpression among histological grades of conventional oral squamous cell carcinoma (COSCC), as well as comparison with verrucous carcinoma (VC) has been less investigated. STUDY DESIGN: Immunohistochemical expression of cyclin B1 was compared with various clinicopathological features in 30 primary COSCC and 31 primary VC cases. RESULT: Cyclin B1 showed significant overexpression for some clinical features for both the variants of oral squamous cell carcinoma. In histopathological variants, statistical significance was observed among grades of COSCC, as well as COSCC and its grades with VC. The concomitant increase in cyclin B1 overexpression from VC to grades COSCC was observed. CONCLUSION: Our study findings draw attention to cyclin B1 overexpression is involved in early carcinogenesis, cell differentiation and tumor proliferation.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/patología , Ciclina B1/biosíntesis , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The role of human papillomavirus (HPV) infections in the development of verrucous carcinoma, a well-differentiated variant of squamous cell carcinoma with difficult differential diagnosis, is controversial in the literature. In this study, we analysed verrucous carcinoma from different origins for the presence and activity of a broad spectrum of HPV types, and carefully reviewed the histopathological features. A random series of 27 formalin-fixed, paraffin-embedded specimens of verrucous carcinoma was taken, representing the head and neck region (n=6), anogenital area (n=16) and extragenital skin region (n=5). After review of the histological slides, all samples were subjected to different polymerase chain reaction-based HPV detection techniques, together detecting a total of 83 HPV types, including both mucosal and cutaneous types. Histological revision was carefully performed. Lesions with keratinised papillae, blunt stromal invaginations and minimal cytological atypia were considered verrucous carcinoma. Condylomatous lesions with viral changes were defined as giant condyloma. Verrucous lesions that did not meet those criteria were classified as verrucous hyperplasia. Tumours with stromal infiltration were considered as invasive squamous cell carcinoma. Histological revision revealed that 13 out of 27 cases were verrucous carcinoma (one showing a double infection with HPV 35 and 45), 5 invasive squamous cell carcinomas, 5 verrucous hyperplasia (one with a double infection with HPV 4 and 8), 1 pseudoepitheliomatous hyperplasia and 3 giant condylomas. All three giant condylomas were low-risk HPV positive (HPV 6 and 11) and showed active mRNA transcription. None of the HPV-positive samples tested positive for diffuse p16(INK4A) staining. In conclusion, our results do not support a causal role of HPV in the development of verrucous carcinoma. Testing for LR-HPV, particularly HPV 6 and 11, may help in the differential diagnosis of lesions suspicious of verrucous carcinoma as those testing positive for LR-HPV most likely represent giant condylomas.
Asunto(s)
Tumor de Buschke-Lowenstein/virología , Carcinoma Verrugoso/virología , Neoplasias de Cabeza y Cuello/virología , Infecciones por Papillomavirus/virología , Neoplasias Cutáneas/virología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Tumor de Buschke-Lowenstein/metabolismo , Tumor de Buschke-Lowenstein/patología , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , ADN Viral/análisis , Diagnóstico Diferencial , Femenino , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Adulto JovenRESUMEN
AIMS: To investigate the expression of microRNAs miR-21, miR-31, miR-203, miR-125a-5p and miR-125b and proteins phosphatase and tensin homologue (PTEN) and p63 in verrucous carcinoma (VC) of the head and neck. METHODS AND RESULTS: Thirty cases of VC, 50 cases of conventional squamous cell carcinoma (SCC) and 30 samples of normal epithelium of the head and neck were included. Real-time polymerase chain reaction and immunohistochemistry were used to analyse the expression of microRNAs and proteins, respectively. In comparison to normal epithelium, miR-21 was overexpressed in both VC and SCC and miR-31 was overexpressed in VC and in well- and moderately differentiated SCC. Levels of miR-203 were elevated in VC but unaltered or reduced in SCC, and levels of miR-125a-5p and miR-125b were reduced in VC but unaltered in SCC. PTEN was down-regulated in both VC and SCC, whereas p63 was down-regulated in VC but up-regulated in SCC. Differential expression of p63 in VC correlated inversely with the expression of miR-21 and miR-203. CONCLUSIONS: Differences between VC, SCC and normal epithelium in expression profiles of investigated molecules indicate their association with the pathogenesis and clinicopathological characteristics of VC. Our results suggest that some microRNAs and proteins, particularly miR-125b, miR-203 and p63, might be useful in the diagnosis of VC.
Asunto(s)
Carcinoma Verrugoso/genética , Carcinoma Verrugoso/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Fosfohidrolasa PTEN/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/patología , Estudios de Casos y Controles , Femenino , Expresión Génica , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
PURPOSE: Squamous cell carcinoma (SCC) is the most prevalent malignant neoplasm of the oral cavity and oral verrucous carcinoma (OVC) is a verrucous variant of SCC. The purpose of this study was to examine the clinical classification of OVC and see for any difference in the biological behavior between OVC and CSS. METHODS: OVC and SCC were divided into 5 groups: the exogenic type of OVC (eOVC), cystoid type of OVC (cOVC) and infiltrative type of OVC (iOVC); well differentiated SCC (wdSCC), and medium/poorly differentiated SCC (m/pdSCC). A normal mucosa (NM) group was also created and studied. Stereology was used to measure and describe the morphological parameters of the nucleus to cytoplasm ratio (Vnp), desmosomes, mitochondria, etc. Analysed were also the nucleus volume density (Vv), Vnp, desmosomes and intracellular desmosomes number density (Nv), which were observed by stereology. RESULTS: We noticed some statistically significant differences in the morphological parameters among the 6 groups including the Vv (p<0.05), the Vnp (p<0.05), the number density of desmosomes (p<0.05), and the Nv (p<0.05). CONCLUSION: This study provides a theoretical basis for the clinical diagnosis and therapy of OVC.
Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/clasificación , Carcinoma Verrugoso/patología , Neoplasias de la Boca/patología , Boca/patología , Adulto , Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrugoso/metabolismo , Desmosomas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Boca/metabolismo , Neoplasias de la Boca/metabolismo , Estadificación de Neoplasias , PronósticoRESUMEN
Human papillomavirus (HPV) has been cited as a possible initiating agent in the pathogenesis of oral cancer. However, the literature tends to be both controversial and inconclusive about the prevalence of HPV and its potential for proliferation in oral squamous cell carcinoma (SCC). The aim of this study was to investigate the cellular proliferation and the presence of HPV in SCC and verrucous carcinoma (VC). Forty-seven samples of SCC were selected and divided into three groups: 39 SCC, 8 VC, and 9 of normal mucosa (control-CT). Quantitative analyses of all groups showed a greater expression of PCNA, followed by Ki-67 and cyclin B1. A significant difference was observed in cyclin B1 expression in the SCC group compared with VC. PCNA, Ki-67, and cyclin B1 were statistically significant when comparing the SCC and CT groups. However, when SCC and VC were compared, there was no difference in Ki-67 expression. Our results showed that only cyclin B1 had an association with histological grade, and that poorly differentiated tumors presented a higher expression of cyclin B1. Therefore, considerable differences in the cellular proliferation between SCC and VC were observed, and no correlation with HPV was established, since all samples were negative for HPV.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Carcinoma Verrugoso/patología , Carcinoma Verrugoso/virología , Proliferación Celular , Neoplasias de la Boca/patología , Neoplasias de la Boca/virología , Anciano , Brasil , Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrugoso/metabolismo , Estudios de Casos y Controles , Ciclina B1/metabolismo , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Neoplasias de la Boca/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismoRESUMEN
BACKGROUND: Invasion and metastasis are two characteristics of malignant tumors, which perform by proteolytic destruction of the components of basement membrane (BM) and cell migration. The aim of this study was to evaluate the immunohistochemical (IHC) assessment of type IV collagen and laminin-332 γ2 (Ln-332 γ2) chain expression in well-differentiated oral squamous cell carcinoma (OSCC) and oral verrucous carcinoma (OVC), because these two lesions have same histopathologic findings whereas they have different biological behaviors. METHODS: Destruction of BM and cell migration were evaluated by IHC in 15 cases of epithelial hyperplasia with no dysplasia (A group), 15 cases of OVC (B group) and 15 cases of well-differentiated OSCC (C group). RESULTS: There was a significant difference in type IV collagen immunohistochemical staining between three groups, but there were no significant differences between B and C groups. Expression of Ln-332 γ2 chain was not detected in A group. Ln-332 γ2 chain labeling index had significantly difference between B and C groups. The number of Ln-332 γ2 chain immunostaining positive cells was less than 5% in B group and over than 5% in C group which there were significantly differences between these two groups. CONCLUSIONS: Isolated immunohistochemical study of type IV collagen does not clearly define that a lesion is invasive or non-invasive and evaluation of Ln-332 γ2 chain expression (cut-off 5%) may be useful as a marker for description of biological differences and diagnosis of OVC from well-differentiated OSCC, especially in doubtful cases.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrugoso/metabolismo , Moléculas de Adhesión Celular/biosíntesis , Colágeno Tipo IV/biosíntesis , Neoplasias de la Boca/metabolismo , Adulto , Anciano , Membrana Basal/patología , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/patología , Moléculas de Adhesión Celular/análisis , Movimiento Celular , Distribución de Chi-Cuadrado , Colágeno Tipo IV/análisis , Diagnóstico Diferencial , Epitelio/patología , Femenino , Humanos , Hiperplasia , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , KalininaRESUMEN
Verrucous hemangioma represents a rare congenital vascular proliferation that may be mistaken for angiokeratoma. Histopathological examination of a deep biopsy is necessary to confirm the diagnosis of verrucous hemangioma based on its involvement of the deep dermis and subcutaneous tissue. We present two cases of verrucous hemangioma and discuss the clinicopathologic and immunohistochemical findings.
Asunto(s)
Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/patología , Hemangioma/metabolismo , Hemangioma/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Niño , Preescolar , Dermis/metabolismo , Dermis/patología , Humanos , MasculinoRESUMEN
Verrucous carcinoma (VC) of the skin is relatively rare. The author reports 5 Japanese cases of VC of the skin. The age ranged from 63 to 91 years with a median of 70 years. The locations were hand in 1 case, lip in 1, face in 1, and foot sole in 2. The size ranged from 0.8 cm to 30 mm with a median of 1.5 cm. Grossly, all the cases showed elevated verrucous tumors. Histologically, the tumors were composed of squamous epithelial cells with minimal cellular atypia arranged in a verrucous pattern. One case showed koilocytosis. Neutrophilic abscesses were seen in 3 cases. Microinvasion was recognized in 2 cases. Focus of less differentiated squamous cell carcinoma was seen in the VC in 1 case. Actinic karatosis or squamous cell carcinoma in situ contiguous to VC was seen in 1 case. Definite precedent lesions were not recognized in any of the cases. Immunohistochemically, VCs of the skin were negative for human papilloma virus antigens in the 2 cases examined. p53 protein was expressed in all the VCs and accentuated in the basal and microinvasive parts. The Ki-67 antigen was also expressed in all the VCs, and it was mainly observed in the basal and microinvasive areas. These findings suggest that (1) VC of the skin can occur in any skin sites, (2) VC of the skin can transform into less differentiated squamous cell carcinoma, and (3) VC of the skin may be associated with squamous cell carcinoma in situ.
Asunto(s)
Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/patología , Queratosis Actínica/patología , Neoplasias Cutáneas/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrugoso/metabolismo , Femenino , Humanos , Queratosis Actínica/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Primarias Múltiples , Neoplasias Cutáneas/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
The epithelium adjacent to an oral squamous cell carcinoma is at risk of undergoing precancerous changes. Even after such changes occur, however, the adjacent epithelium remains histologically similar to normal mucosa. We investigated five argyrophilic nucleolar organizer region (AgNOR)-related features in samples of oral verrucous carcinoma (VeCa) and their corresponding adjacent lining epithelium (adj. VeCa). Morphometric characteristics of AgNORs in oral adj. VeCa and oral VeCa were compared to normal mucosa epithelium, squamous cell carcinoma and oral mucosa epithelium adjacent to squamous cell carcinoma findings that we published earlier. Although adj. VeCa and normal oral mucosa were histologically similar, total AgNOR volume differentiated adj. VeCa from normal oral mucosa, but revealed no significant difference between VeCa and adj. VeCa. Total AgNOR volume/nuclear volume discriminated VeCa from adj. VeCa and normal oral mucosa. Certain AgNOR parameters provide a complementary tool for discriminating VeCa from adj. VeCa and normal oral mucosa, and also for detecting incipient malignant changes in epithelium adjacent to VeCa. Use of the AgNOR technique is cost-effective, because it can be performed on paraffin sections.
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Carcinoma Verrugoso/metabolismo , Epitelio/metabolismo , Neoplasias de la Boca/metabolismo , Región Organizadora del Nucléolo/fisiología , Adulto , Anciano , Biomarcadores de Tumor , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16(INK4A) and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16(INK4A) and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16(INK4A) and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16(INK4A) expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.
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Biomarcadores de Tumor/análisis , Carcinoma Verrugoso/patología , Proteínas de Ciclo Celular/biosíntesis , Infecciones por Papillomavirus/complicaciones , Neoplasias del Pene/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/virología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Humanos , Inmunohistoquímica , Antígeno Ki-67/biosíntesis , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Neoplasias del Pene/metabolismo , Neoplasias del Pene/virología , Reacción en Cadena de la Polimerasa , Proteína de Retinoblastoma/biosíntesis , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
Verrucous carcinoma of the esophagus (VCE) is a rare variant of squamous cell cancer, with a puzzling clinical, etiological, and molecular profile. The etiological involvement of human papillomavirus (HPV) in the cancer's natural history is controversial. This study considers 9 cases of VCE, focusing on patients' clinical history before surgery, histologic phenotype, immunophenotype (epidermal growth factor receptor [EGFR], E-cadherin, cyclin D1, p16, and p53 expression), HPV infection, and TP53 gene mutational status (exons 5-8). Using 3 different molecular test methods, not one of these cases of VCE featured HPV infection. The only case with synchronous nodal metastasis was characterized by a TP53 missense point mutation in association with high EGFR and low E-cadherin expression levels. In conclusion, HPV infection is probably not involved with VCE, while TP53 gene mutation, EGFR overexpression, and E-cadherin loss might fuel the tumor's proliferation and lend it a metastatic potential.
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Carcinoma Verrugoso/virología , Neoplasias Esofágicas/virología , Infecciones por Papillomavirus/virología , Adulto , Anciano , Cadherinas/metabolismo , Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/patología , Receptores ErbB/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma, occurring mostly in oral mucosa. To clarify the role of human papillomavirus (HPV) in VC tumorigenesis, we investigated localization and genotypes of HPV and p53 expression in oral VC. METHODS: We studied paraffin-embedded specimens of 23 VCs and 10 control non-neoplastic lesions in oral mucosa. To investigate HPV infection, HPV genotypes and p53 expression, we respectively employed in situ hybridization (ISH), sequence analysis following short PCR fragment-PCR assay and immunohistochemistry. RESULTS: Of the 23 VC specimens, 11 (48%) had HPV-DNA (detectable by PCR), and 6 (26%) had intranuclear HPV in the upper portion of the squamous epithelium (detectable by ISH). Nine of the 11 PCR-positive specimens showed multiple infections with low- and high-risk HPVs. No HPV-16 infection was detected. Although HPV-6 and HPV-18 were frequently detected by PCR, no HPV could be found in control specimens by ISH. p53 expression was inversely correlated with HPV infection. CONCLUSION: Thus, multiple infections with low- and high-risk HPVs and their rapid replication during hyperkeratinization may participate in the histogenesis of oral VC. Oral VC tumorigenesis may involve the inactivation of p53, which is associated with HPV infection.
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Carcinoma Verrugoso/metabolismo , Carcinoma Verrugoso/virología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/virología , Infecciones por Papillomavirus/complicaciones , Proteína p53 Supresora de Tumor/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Verrugoso/patología , Estudios de Casos y Controles , Niño , ADN de Neoplasias/genética , ADN Viral/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Genotipo , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidad , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/patogenicidad , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Mucosa Bucal/virología , Neoplasias de la Boca/patología , Infecciones por Papillomavirus/diagnóstico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Verrucous carcinoma, a variant of well-differentiated squamous cell carcinoma, is usually described in the literature as arising in the oral cavity, skin, and larynx. The reports on verrucous carcinoma arising in the genital tract, usually originating in the vagina, vulva, or uterine cervix, are few. Verrucous carcinoma arising in the ovary has not been previously reported. In this article, a unique hybrid carcinoma, a large aggressive verrucous carcinoma in combination with squamous carcinoma of the left ovary and synchronously occurring with a squamous cell carcinoma in the endometrium, is presented. This unique case of a hybrid carcinoma includes the first-known case of this type of carcinoma involving the ovary. The negative cervical evaluation findings, together with the histologic patterns of the tumors in the uterus and the ovary, support the conclusion that these 2 carcinomas are synchronous, one arising in the left ovary and the other arising in the uterus.
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Carcinoma de Células Escamosas/patología , Carcinoma Verrugoso/patología , Neoplasias Endometriales/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma Verrugoso/metabolismo , Diverticulitis/patología , Neoplasias Endometriales/metabolismo , Femenino , Reflujo Gastroesofágico/patología , Humanos , Hipertensión/patología , Neoplasias Primarias Múltiples/metabolismo , Neoplasias Ováricas/metabolismo , Taquicardia Supraventricular/patologíaRESUMEN
BACKGROUND: Verrucous carcinoma (VC) should be considered a distinct clinicopathologic entity different from the more common oral squamous cell carcinoma (OSCC) because of its unique biological behavior. Best way to understand the behavior of these carcinomas is to study them by means of molecular methods, especially in tumor progression tests and Bcl-X is an important antiapoptotic member of the Bcl-2 family and is one of the newest and most useful markers to determine the aggressiveness of many carcinomas. The relationship between this Bcl-X protein and carcinomatous behavior toward it is not studied extensively, which we attempted to evaluate using immunohistochemical analysis in selected carcinomas of the head and neck region. METHOD: We studied Bcl-X protein expression in sections of thirty OSCC and ten VC samples and correlated this with tumor differentiation. RESULTS: There was a significant difference in cytoplasmic staining of Bcl-X expression with statistical analysis (P < 0.005) for VC and OSCC when compared as a group. No significance was seen among the different histological grades of OSCC and when compared with VC individually. CONCLUSION: The significant result between OSCC and VC suggests that their biologic course is comparable and can be helpful in differentiating them with each other for establishment of a better treatment protocol.