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Abstract 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. © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
Resumo Introdução: Marcadores de proliferação têm um papel significativo no comportamento biológico dos tumores. A geminina é um inibidor conhecido do ciclo celular e da replicação do DNA e não foi relatada anteriormente em carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço. Objetivo: Investigar os marcadores de proliferação ki67, MCM2 e geminina em carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço. Método: Foram submetidos 40a casos de cada tumor à imunocoloração com ki67, MCM2 e geminina, seguida pela avaliação do índice de marcação.Também foram determinadas as razões MCM2/ki67 e geminina/ki67 e o teste t foi usado na análise estatística (p < 0,05). Resultados: Não houve diferença significativa no ki67 (p = 0,06) e no MCM2 (p = 0,46) entre carcinomas basocelulares e espinocelulares; no entanto, o índice de marcação da geminina foi significativamente maior no carcinomas espinocelulares em comparação ao carcinomas basocelulares (p < 0,001). Somente a razão geminina/ki67 mostrou diferença significativa entre os dois tumores, a razão mostrou números significativamente mais altos nos carcinomas espinocelulares (p = 0,015). Conclusões: A geminina pode ser considerada um fator efetivo na patogênese dos carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço e pode ser um dos elementos responsáveis pela diferença entre o comportamento biológico desses tumores.
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Objective To analyze the positive expression levels of p16 ( p16ink4a), cell cycle factor geminin and Ki-67 in low-grade squamous intraepithelial lesions ( LSIL),and to further explore the ability of these indicators to evaluate the progression of LSIL patients. Methods From January 2015 to June 2018,276 cervical specimens from Jiading District Central Hospital of Shanghai were retrospectively studied, and 148 LSIL patients were selected. According to the results of the second examination,LSIL patients were divided into three groups: (1) no lesion (natural regression) group 90 cases; (2) LSIL persistent group 38 cases; (3) high-grade Squamous Intraepithelial Lesion (HSIL) group 20 cases. Immunohistochemistry was performed on the first biopsy tissues and the relative positive ratios of p16, geminin and Ki-67 were calculated. Spearman correlation analysis identified the correlation between the above indicators and the progress of the disease; ROC curve was used to calculate the best diagnostic value of each indicator,and multivariate logistic regression analysis was included to explore the ability of the above indicators to assess the risk of patients progressing to HSIL. Results In the HSIL group, p16 ( 51. 26 ± 17. 15)%, geminin relative positive ratio ( 45. 92 ± 15. 70)% was higher than those in the LSIL group(( 43. 71 ± 11. 84)%, (21. 68± 14. 47)%) and regression group (( 17. 92 ± 9. 60)%, ( 0. 16 ± 0. 03)%) . The difference were statistically significant ( F＝2. 922, 2. 751, all P＜0. 05) . Spearman correlation analysis showed that the relative positive ratio of p16 ( r＝0. 27,P＝0. 014) and geminin ( r＝0. 44,P＜0. 001) presented a notable positive correlation with the progression of the disease. Under the ROC curve,the best diagnostic values of p16, geminin and Ki-67 were 38. 9%, 32. 5% and 18. 6%, respectively. Multivariate logistic regression analysis showed that the relative positive ratio of p16 was higher than 38. 9%(OR＝4. 366,P＝0. 006),and geminin was higher than 32. 5%( OR ＝ 5. 392, P ＝ 0. 011 ) had a higher risk of progression to HSIL. Conclusion p16 and geminin may be effective biomarkers for identifying patients with advanced LSIL.
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INTRODUCTION: Gingiva fibromatosis is a relatively rare condition characterized by diffuse enlargement of the gingiva, which is caused by expansion and accumulation of the connective tissue. OBJECTIVE: The aim of the present study was to investigate proliferative and apoptotic biomarker expression in normal gingiva and two forms of gingival fibromatosis. METHODS: Archived tissue specimens of hereditary gingival fibromatosis, gingival fibromatosis and dental abnormality syndrome and normal gingiva were subject to morphological analysis and immunohistochemical staining. The results were analyzed statistically. RESULTS: Proteins associated with proliferation were found in the nuclei of epithelial cells from the basal and suprabasal layers, whereas apoptotic proteins were detected in the cytoplasm of the upper layers of the epithelium. Increased expressions of minichromosome maintenance proteins 2 and 5 were observed in the gingival fibromatosis and dental abnormality syndrome samples. In contrast, geminin expression was higher in normal gingiva samples. No difference in the expression of apoptotic proteins was observed among the groups. CONCLUSION: Our findings support a role for augmented proliferation of epithelial cells within the overgrown tissues associated with gingival fibromatosis or dental abnormality syndrome. However, our data suggest that different biological mechanisms may account for the pathogenesis of different types of gingival fibromatosis.
Subject(s)
Female , Humans , Male , Cell Cycle Proteins/analysis , Epithelial Cells/chemistry , Fibromatosis, Gingival/metabolism , Nuclear Proteins/analysis , Tooth Abnormalities/metabolism , Biomarkers/analysis , Case-Control Studies , Cross-Sectional Studies , Epithelial Cells/pathology , Fibromatosis, Gingival/genetics , Fibromatosis, Gingival/pathology , Immunohistochemistry , Tooth Abnormalities/genetics , Tooth Abnormalities/pathology , /analysisABSTRACT
Geminin is a multifunctional protein which localizes in nucleus,it has complicated structural and functional domains.Geminin plays very important roles in cell proliferation,embryonic development,tumorigenesis and so on.Geminin affects cell proliferation through influence on the important events in cell cycle phases.There are many mechanisms by which Geminin can control DNA replication,inhibit centrosome over-duplication,promote G2/M phase progression,maintain proper cytokinesis.At different development stages,Geminin acts as an inhibitor or inducer in regulating embryonic development,especially in nervous system formation.Geminin also plays a regulative role in eye development and embryonic development through the interactions with homeobox genes or proteins Six3 and Hox,Geminin functions as a coordinator of cell proliferative and differentiative control.Recently,Geminin was found to have relationship with cancer,the study on the function of Geminin in cancer has been a meaningful aspect.Geminin can act as a marker to evaluate progression and prognosis in cancer.It may be a novel molecular target in therapy of cancer.The activity of Geminin is regulated by transcription level and post-transcription level,the post-transcriptional regulation of Geminin protein may take the main position.