RESUMO
INTRODUCTION: Proliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck. OBJECTIVES: We aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas. METHODS: Forty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p<0.05). RESULTS: There was no significant difference in ki67 (p=0.06) and MCM2 (p=0.46) between cutaneous basal and squamous cell carcinomas; however, geminin LI was significantly higher in squamous cell carcinomas compared to cutaneous basal cell carcinomas (p<0.001). Only geminin/ki67 showed a significant difference between the two tumors with the ratio showing significantly higher numbers in squamous cell carcinomas (p=0.015). CONCLUSIONS: Geminin could be regarded as an effective factor in the pathogenesis of head and neck cutaneous cutaneous basal cell carcinomas and squamous cell carcinomas and may be one of the responsible elements in the difference between the biologic behavior of these tumors.
Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Geminina , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Biomarcadores Tumorais/análise , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Geminina/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer. METHODS: We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit. RESULTS: We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%). CONCLUSIONS: We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample.
Assuntos
Ciclina E/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Biópsia Líquida/métodos , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Citodiagnóstico/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/cirurgia , Lesões Pré-Cancerosas/virologia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia , Displasia do Colo do Útero/virologiaRESUMO
ABSTRACT Introduction/Background: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. Material and Methods: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. Results: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. Conclusion: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.
Assuntos
Humanos , Masculino , Feminino , Carcinoma de Células Renais/patologia , Antígeno Nuclear de Célula em Proliferação/química , Antígeno Ki-67/análise , Proliferação de Células , Componente 2 do Complexo de Manutenção de Minicromossomo/química , Neoplasias Renais/patologia , Imuno-Histoquímica , Variações Dependentes do Observador , Gradação de Tumores , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
This study aimed to assess the immunoexpression of cell proliferation markers (Ki-67 and Mcm-2) in oral tongue cancer, correlating it with patients' age and prognostic indicators. Sample was composed of 22 cases under 40 years and 22 over 50 years of age. Clinical staging and histological grade of malignancy were obtained. Cell proliferation was evaluated through labeling indices. Statistical analysis was performed (p<0.05 for statistical significance). Most young patients were stages III/IV (n=13/65 %) and most older patients were stages I/II (n=11/61.1 %) (p>0.05). Mean Ki-67-LI in young and older patients was 42.4 % and 44.15 %, respectively (p>0.05). Mean Mcm-2-LI was higher in older (63.6 %) than in young patients (55.75 %) (p<0.05). We found that young patients presented more aggressive lesions in comparison to older patients, however Mcm-2 expression was significantly higher in older than in young patients. SCC of tongue can be more aggressive in young patients, and this may not be related to cell proliferation. Our findings for Mcm-2 LI and Ki-67 LI suggests that Mcm-2 could be a more sensitive marker for cell proliferation.
Este estudio tuvo como objetivo evaluar la inmunoexpresión de marcadores de proliferación celular (Ki-67 y Mcm-2) en el cáncer de lengua oral, correlacionándolo con la edad de los pacientes y los indicadores pronósticos. La muestra estuvo compuesta por 22 personas menores de 40 años y 22 personas mayores de 50 años. Se identificaron los estadios clínicos y el grado histológico de malignidad. La proliferación celular se evaluó mediante índices de marcado. Se realizó análisis estadístico (p <0,05 para significación estadística). La mayoría de los pacientes jóvenes eran estadios III / IV (n = 13/65 %) y la mayoría de los pacientes mayores eran estadios I / II (n = 11 / 61,1 %) (p> 0,05). La media de Ki-67-LI en pacientes jóvenes y mayores fue 42,4% y 44,15%, respectivamente (p> 0,05). La media de Mcm-2-LI fue mayor en pacientes mayores (63,6 %) que en pacientes jóvenes (55,75 %) (p <0,05). Se encontró que los pacientes jóvenes presentaron lesiones más agresivas en comparación con los pacientes mayores, sin embargo la expresión de Mcm-2 fue significativamente mayor en pacientes mayores que en pacientes jóvenes. SCC de la lengua puede ser más agresivo en pacientes jóvenes, y esto no puede estar relacionado con la proliferación celular. Nuestros hallazgos para Mcm-2 LI y Ki-67 LI sugieren que Mcm-2 podría ser un marcador más sensible para la proliferación celular.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/imunologia , Antígeno Ki-67/metabolismo , Neoplasias Bucais/imunologia , Fatores Etários , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Imuno-Histoquímica , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Neoplasias Bucais/metabolismo , Prognóstico , Neoplasias da Língua/metabolismoRESUMO
INTRODUCTION/BACKGROUND: Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67. MATERIAL AND METHODS: n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers. RESULTS: Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis. CONCLUSION: Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.
Assuntos
Carcinoma de Células Renais/patologia , Proliferação de Células , Antígeno Ki-67/análise , Neoplasias Renais/patologia , Componente 2 do Complexo de Manutenção de Minicromossomo/química , Antígeno Nuclear de Célula em Proliferação/química , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Variações Dependentes do ObservadorRESUMO
Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors.
Assuntos
Ameloblastoma/metabolismo , Carcinoma/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Antígeno Ki-67/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Componente 3 do Complexo de Manutenção de Minicromossomo/metabolismo , Adolescente , Adulto , Idoso , Ameloblastoma/patologia , Carcinoma/patologia , Proliferação de Células , Criança , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Imuno-Histoquímica , Ameloblastoma , Ameloblastoma , Carcinoma , Carcinoma , Proliferação de Células , NEOPLASIAS DE LA CABEZA Y EL CUELLO , Metabolismo , NEOPLASIAS DE LA CABEZA Y EL CUELLO , Patologia , Antígeno Ki-67 , Componente 2 do Complexo de Manutenção de Minicromossomo , Biomarcadores TumoraisRESUMO
The aim of this comparative observational study was to compare the proliferative activity of dental follicles surrounding impacted maxillary canines and mandibular third molars. Following extraction, forty follicles of the impacted mandibular third molars and 40 follicles of the impacted maxillary canines were removed. Epithelial cell proliferative activity of these samples was assessed using immunohistochemical labeling for Ki-67, minichromosome maintenance 2 (MCM-2) protein and epithelial growth factor receptor (EGFR). Intensity and extent of Ki-67, MCM-2 and EGFR expressions were evaluated by a scoring formula. The lining epithelium of the maxillary canine follicles had mean scores of 4.65±0.27 for Ki-67, 1.25±0.33 for MCM-2 and 7.30±0.23 for EGFR which were not significantly different than those expressed in the mandibular third molar follicles (4.46±0.26 for Ki-67, 1.39±0.33 for MCM-2 and 7.21±0.20 for EGFR). The expression of Ki-67 and MCM-2 could not be detected in the epithelial remnants within the connective tissue in both groups. EGFR expression, detected in the epithelial remnants in both groups, was not significantly different (7.28±0.14 in the canine group as opposed to 7.21±0.16 in the third molar group). Based on these findings, it can be deduced that impacted mandibular third molars and maxillary canines carry similar risk of pathology development.
El objetivo fue comparar la actividad proliferativa de los folículos dentarios que rodean a dientes caninos maxilares y terceros molares mandibulares impactados. Luego de realizada la extracción dentaria, se removieron 40 folículos dentarios de los terceros molares mandibulares impactados y 40 de caninos maxilares impactados. Se evaluó la actividad proliferativa de las células epiteliales de estas muestras mediante marcaje inmunohistoquímico para Ki-67, para la proteína de mantenimiento minicromosoma 2 (MCM-2) y para el receptor del factor de crecimiento epitelial (EGFR). Se evaluó la intensidad y extensión de Ki-67, MCM-2 y las expresiones de EGFR mediante una fórmula de puntuación. El epitelio de revestimiento de los folículos correspondientes a los caninos maxilares presentaron valores promedios de 4,65±0,27 para Ki-67, 1,25±0,33 para MCM-2 y 7,30±0,23 para EGFR, que no fueron significativamente diferentes de los expresados en los folículos de terceros molares mandibulares (4,46±0,26 para Ki-67, 1,39±0,33 para MCM-2 y 7,21±0,20 para EGFR). La expresión de Ki-67 y MCM-2 no pudo ser detectada en los restos epiteliales dentro del tejido conectivo en ambos grupos. La expresión de EGFR, detectada en los restos epiteliales en ambos grupos, no fue significativamente diferente (7,28±0,14 en el grupo de los caninos, y 7,21±0,16 en el grupo de los terceros molares). Sobre la base de estos resultados, se puede deducir que la retención de terceros molares y caninos maxilares conlleva un riesgo similar para el desarrollo de patología.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Dente Impactado , Antígeno Ki-67/metabolismo , Saco Dentário/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Receptores ErbB/metabolismo , Imuno-Histoquímica , Dente Canino , Proliferação de Células , Estudo Observacional , Dente SerotinoRESUMO
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.
Assuntos
Aneuploidia , Carcinoma Verrucoso/patologia , Proteínas de Ciclo Celular/metabolismo , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Proteínas Nucleares/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Verrucoso/genética , Carcinoma Verrucoso/metabolismo , Proliferação de Células , Transformação Celular Neoplásica , DNA de Neoplasias/genética , Feminino , Geminina , Humanos , Citometria por Imagem , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Leucoplasia Oral/genética , Leucoplasia Oral/metabolismo , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Estudos RetrospectivosRESUMO
Evaluation of cell cycle using antibodies against nuclear proteins involved in regulating DNA replication has gained special interest in the effort to predict biologic behavior of benign and malignant tumors. The aim of this study was to analyze the expression of minichromosome maintenance 2, Ki-67, and geminin in oral nevi and melanomas. Expression of these cell proliferation markers was evaluated by immunohistochemistry in 49 oral melanocytic lesions, including 38 intramucosal nevi and 11 primary oral melanomas. The labeling index of each proliferation marker was assessed considering the percentage of cells expressing nuclear positivity out of the total number of cells, counting 1000 cells per slide. Minichromosome maintenance 2, Ki-67, and geminin were rarely expressed in intramucosal nevi, in contrast to oral melanomas, which showed high levels of these cell proliferation markers, particularly minichromosome maintenance 2, indicating it is a more sensitive marker in primary oral melanomas than Ki-67 and geminin. These results indicate that these markers may be involved in the pathogenesis of oral melanomas and could be eventually useful as an additional diagnostic tool for differential diagnosis of oral benign and malignant melanocytic lesions.