Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma

Introduction: Oral verrucous carcinoma is a special form of well-differentiated squamous cell carcinoma which possesses specific clinical, morphologic and cytokinetic features that differ from other types of oral cancers and hence diagnosis requires immense experience in histopathology. Hence it is...

Full description

Bibliographic Details
Main Authors: M.K. Harishankar, A. Mathan Mohan, A. Vinod Krishnan, Arikketh Devi
Format: Article
Language:English
Published: Elsevier 2019-01-01
Series:Brazilian Journal of Otorhinolaryngology
Online Access:http://www.sciencedirect.com/science/article/pii/S1808869417301635
_version_ 1818347626283663360
author M.K. Harishankar
A. Mathan Mohan
A. Vinod Krishnan
Arikketh Devi
author_facet M.K. Harishankar
A. Mathan Mohan
A. Vinod Krishnan
Arikketh Devi
author_sort M.K. Harishankar
collection DOAJ
description Introduction: Oral verrucous carcinoma is a special form of well-differentiated squamous cell carcinoma which possesses specific clinical, morphologic and cytokinetic features that differ from other types of oral cancers and hence diagnosis requires immense experience in histopathology. Hence it is certainly important to distinguish such a lesion from other oral tumors as treatment strategies vary widely between them. Objective: In search of a critical diagnostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma, Notch4 receptor, one of the key regulatory molecules of the Notch signaling family has been aberrantly activated in the progression of several types of tumors. However its function in oral verrucous carcinoma remains unexplored. Thus the present study aims in determining the differential expression pattern of Notch4 in oral verrucous carcinoma and oral squamous cell carcinoma. Methods: Ten patients reported positive for oral cancer (5 patients with oral verrucous carcinoma and 5 patients with oral squamous cell carcinoma). Five normal tissue samples were also obtained and evaluated for clinicopathological parameters and immunohistochemistry, western blotting and real time polymerase chain reaction for Notch4 expression. Results: Our results reveal that the expression of Notch4 was considerably high in oral squamous cell carcinoma lesions compared to normal tissue, whereas in oral verrucous carcinoma, irrespective of the clinicopathological features, complete regulação descendente of Notch4 was observed. Conclusions: These preliminary findings strongly support the fact that Notch4 is downregulated in oral verrucous carcinoma and could be considered as a suitable prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma. This distinguishing marker can help in improving therapeutic options in patients diagnosed with oral verrucous carcinoma. Resumo: Introdução: O carcinoma verrucoso de cavidade oral é uma forma especial de carcinoma de células escamosas bem diferenciada que tem características clínicas, morfológicas e citocinéticas específicas que diferem de outros tipos de cânceres orais. Por essa razão, o diagnóstico requer grande experiência em histopatologia. Portanto, é certamente importante distingui-lo de outros tumores orais, pois as respectivas estratégias de tratamento variam muito. Objetivo: Em busca de um marcador de diagnóstico crítico na distinção entre o carcinoma verrucoso e o carcinoma de células escamosas de cavidade oral, o receptor Notch4, uma das principais moléculas reguladoras da família de sinalizadores Notch, foi ativado de maneira anormal na progressão de vários tipos de tumores. No entanto, sua função no carcinoma verrucoso permanece inexplorada. Assim, o presente estudo tem como objetivo determinar o padrão de expressão diferencial de Notch4 no carcinoma verrucoso e de células escamosas de cavidade oral. Método: Dez pacientes tiveram resultado positivo para câncer oral (cinco pacientes com carcinoma verrucoso e cinco pacientes com carcinoma de células escamosas) e cinco amostras normais foram também obtidas. Além da avaliação dos parâmetros clínico-patológicos, foram feitos análise imuno-histoquímica, Western Blot e reação de polimerase em cadeia em tempo real para a expressão de Notch4. Resultados: Nossos resultados revelam que a expressão de Notch4 foi consideravelmente alta em carcinomas de células escamosas em comparação com os tecidos normais, enquanto que no carcinoma verrucoso, independentemente das características clínico-patológicas, observou-se regulação descendente completa de Notch4. Conclusão: Esses achados preliminares apoiam fortemente o fato de que Notch4 estava regulado para baixo no carcinoma verrucoso oral e poderia ser considerado um marcador prognóstico adequado para distinguir entre carcinoma verrucoso e carcinoma de células escamosas de cavidade oral. Esse marcador distintivo pode ajudar a melhorar as opções terapêuticas em pacientes com diagnóstico de carcinoma verrucoso oral. Keywords: Oral verrucous carcinoma, Oral squamous cell carcinoma, Notch4, Prognostic marker, Palavras-chave: Carcinoma verrucoso oral, Carcinoma de células escamosas oral, Notch4, Marcador prognóstico
first_indexed 2024-12-13T17:37:09Z
format Article
id doaj.art-c80ccccf557d45889ca4e37c579a5764
institution Directory Open Access Journal
issn 1808-8694
language English
last_indexed 2024-12-13T17:37:09Z
publishDate 2019-01-01
publisher Elsevier
record_format Article
series Brazilian Journal of Otorhinolaryngology
spelling doaj.art-c80ccccf557d45889ca4e37c579a57642022-12-21T23:36:53ZengElsevierBrazilian Journal of Otorhinolaryngology1808-86942019-01-018511116Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinomaM.K. Harishankar0A. Mathan Mohan1A. Vinod Krishnan2Arikketh Devi3SRM University, School of Bioengineering, Department of Genetic Engineering, Kattankulathur, IndiaKarpaga Vinayaga Institute of Medical and Dental Sciences, Department of Oral and Maxillofacial Surgery, Oral Cancer Foundation, Kancheepuram, IndiaKarpaga Vinayaga Institute of Medical and Dental Sciences, Department of Oral and Maxillofacial Surgery, Oral Cancer Foundation, Kancheepuram, IndiaSRM University, School of Bioengineering, Department of Genetic Engineering, Kattankulathur, India; Corresponding author.Introduction: Oral verrucous carcinoma is a special form of well-differentiated squamous cell carcinoma which possesses specific clinical, morphologic and cytokinetic features that differ from other types of oral cancers and hence diagnosis requires immense experience in histopathology. Hence it is certainly important to distinguish such a lesion from other oral tumors as treatment strategies vary widely between them. Objective: In search of a critical diagnostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma, Notch4 receptor, one of the key regulatory molecules of the Notch signaling family has been aberrantly activated in the progression of several types of tumors. However its function in oral verrucous carcinoma remains unexplored. Thus the present study aims in determining the differential expression pattern of Notch4 in oral verrucous carcinoma and oral squamous cell carcinoma. Methods: Ten patients reported positive for oral cancer (5 patients with oral verrucous carcinoma and 5 patients with oral squamous cell carcinoma). Five normal tissue samples were also obtained and evaluated for clinicopathological parameters and immunohistochemistry, western blotting and real time polymerase chain reaction for Notch4 expression. Results: Our results reveal that the expression of Notch4 was considerably high in oral squamous cell carcinoma lesions compared to normal tissue, whereas in oral verrucous carcinoma, irrespective of the clinicopathological features, complete regulação descendente of Notch4 was observed. Conclusions: These preliminary findings strongly support the fact that Notch4 is downregulated in oral verrucous carcinoma and could be considered as a suitable prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma. This distinguishing marker can help in improving therapeutic options in patients diagnosed with oral verrucous carcinoma. Resumo: Introdução: O carcinoma verrucoso de cavidade oral é uma forma especial de carcinoma de células escamosas bem diferenciada que tem características clínicas, morfológicas e citocinéticas específicas que diferem de outros tipos de cânceres orais. Por essa razão, o diagnóstico requer grande experiência em histopatologia. Portanto, é certamente importante distingui-lo de outros tumores orais, pois as respectivas estratégias de tratamento variam muito. Objetivo: Em busca de um marcador de diagnóstico crítico na distinção entre o carcinoma verrucoso e o carcinoma de células escamosas de cavidade oral, o receptor Notch4, uma das principais moléculas reguladoras da família de sinalizadores Notch, foi ativado de maneira anormal na progressão de vários tipos de tumores. No entanto, sua função no carcinoma verrucoso permanece inexplorada. Assim, o presente estudo tem como objetivo determinar o padrão de expressão diferencial de Notch4 no carcinoma verrucoso e de células escamosas de cavidade oral. Método: Dez pacientes tiveram resultado positivo para câncer oral (cinco pacientes com carcinoma verrucoso e cinco pacientes com carcinoma de células escamosas) e cinco amostras normais foram também obtidas. Além da avaliação dos parâmetros clínico-patológicos, foram feitos análise imuno-histoquímica, Western Blot e reação de polimerase em cadeia em tempo real para a expressão de Notch4. Resultados: Nossos resultados revelam que a expressão de Notch4 foi consideravelmente alta em carcinomas de células escamosas em comparação com os tecidos normais, enquanto que no carcinoma verrucoso, independentemente das características clínico-patológicas, observou-se regulação descendente completa de Notch4. Conclusão: Esses achados preliminares apoiam fortemente o fato de que Notch4 estava regulado para baixo no carcinoma verrucoso oral e poderia ser considerado um marcador prognóstico adequado para distinguir entre carcinoma verrucoso e carcinoma de células escamosas de cavidade oral. Esse marcador distintivo pode ajudar a melhorar as opções terapêuticas em pacientes com diagnóstico de carcinoma verrucoso oral. Keywords: Oral verrucous carcinoma, Oral squamous cell carcinoma, Notch4, Prognostic marker, Palavras-chave: Carcinoma verrucoso oral, Carcinoma de células escamosas oral, Notch4, Marcador prognósticohttp://www.sciencedirect.com/science/article/pii/S1808869417301635
spellingShingle M.K. Harishankar
A. Mathan Mohan
A. Vinod Krishnan
Arikketh Devi
Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
Brazilian Journal of Otorhinolaryngology
title Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
title_full Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
title_fullStr Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
title_full_unstemmed Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
title_short Downregulation of Notch4 – a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
title_sort downregulation of notch4 a prognostic marker in distinguishing oral verrucous carcinoma from oral squamous cell carcinoma
url http://www.sciencedirect.com/science/article/pii/S1808869417301635
work_keys_str_mv AT mkharishankar downregulationofnotch4aprognosticmarkerindistinguishingoralverrucouscarcinomafromoralsquamouscellcarcinoma
AT amathanmohan downregulationofnotch4aprognosticmarkerindistinguishingoralverrucouscarcinomafromoralsquamouscellcarcinoma
AT avinodkrishnan downregulationofnotch4aprognosticmarkerindistinguishingoralverrucouscarcinomafromoralsquamouscellcarcinoma
AT arikkethdevi downregulationofnotch4aprognosticmarkerindistinguishingoralverrucouscarcinomafromoralsquamouscellcarcinoma