Oral Diseases (2015) 21, 755–761 doi:10.1111/odi.12343 © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd All rights reserved www.wiley.com
ORIGINAL ARTICLE
The prognostic value of histopathological grading systems in oral squamous cell carcinomas I Sawazaki-Calone1,2, ALCA Rangel1, AG Bueno3, CF Morais4, HM Nagai5, RP Kunz6, RL Souza1, L Rutkauskis1, T Salo2,7,8, A Almangush7,8, RD Coletta2 1
Oral Pathology and Oral Medicine, Dentistry School, Western Paran a State University, Cascavel; 2Department of Oral Diagnosis, 3 Piracicaba Dental School, University of Campinas, Piracicaba; ANATOM Anatomic Pathology Laboratory, Cascavel; 4APC Anatomic Pathology Laboratory, Cascavel; 5UOPECCAN Cancer Hospital, Cascavel; 6Oncology Center of Cascavel (CEONC), Cascavel, Brazil; 7Department of Diagnostics and Oral Medicine, Institute of Dentistry and Oulu University Hospital, University of Oulu, Oulu; 8 Institute of Dentistry, University of Helsinki, Helsinki, Finland
OBJECTIVE: This study evaluated the association of four histopathological grading systems (WHO grading system, malignancy grading of the deep invasive margins (MG), histological risk (HR) model, and tumor budding and depth of invasion (BD) model) with clinicopathological parameters and outcome of 113 oral squamous cell carcinomas to identify their roles in prognosis. METHODS: Demographic and clinical features were obtained from patients’ records. Sections from all paraffin-embedded blocks were evaluated according to the four grading systems. Demographic and clinical associations were analyzed using chi-square test, and correlations between the grading systems were established with the Spearman’s rank correlation test. Survival curves were performed with Kaplan–Meier method, and multivariate analysis based on Cox proportional hazard model was calculated. RESULTS: Significant associations with survival were observed for WHO grading system and BD model in the univariate analysis, but only the BD model was significantly associated with disease outcome as an independent prognostic marker. Age, tumor size, and presence of regional metastasis were also independent markers of reduced survival. CONCLUSION: A significant association between the BD model and outcome of OSCC patients was observed, indicating this new histopathological grading system as a possible prognostic tool. Oral Diseases (2015) 21, 755–761
Correspondence: Iris Sawazaki-Calone, Oral Pathology and Oral Medicine, Dentistry School, Western Parana State University, Rua Universitaria, 2069, Jardim Universitario, CEP: 85819-110, Cascavel, PR, Brazil. Tel: +55 45 33063933, Fax: +55 45 33244566, E-mail: [email protected] Received 3 December 2014; revised 17 March 2015; accepted 20 March 2015
Keywords: oral squamous cell carcinoma; histopathological grading system; survival analysis; prognosis; oral cancer
Introduction Clinical staging of the disease based on TNM classification and location of the tumor are routinely the main criteria for prognostication and treatment of oral squamous cell carcinomas (OSCCs) (Dissanayaka et al, 2012). However, variations in the treatment response and prognosis are high for OSCCs, with some patients presenting tumors at the same site and same clinical stage having prolonged survival, while others may die of metastasis rapidly. In the view of those difficulties, it has been proposed that a detailed histopathological grading of the tumors with specific histopathological scoring systems could help the clinicians in the individualization of treatment and in prognostication of patients with OSCC (Anneroth et al, 1987; Bryne et al, 1992; Brandwein-Gensler et al, 2005; Almangush et al, 2015). The first histopathological grading system for OSCCs was developed by Broders in 1920 (Broders, 1920), which was later adopted for the World Health Organization (WHO) (Barnes et al, 2005). This system takes into account the degree of keratinization of the tumor, levels of cellular and nuclear pleomorphism, and presence of mitotic activity. Later on, many other histopathological grading systems have been proposed for OSCCs in the last century. The malignancy grading of the deep invasive margins (MG) proposed by Bryne and collaborators (Bryne et al, 1992) is a system that scores the degree of keratinization, nuclear polymorphism, pattern of invasion, and lymphoplasmacytic infiltration only in the most invasive areas. This grading system has been used for prognostication and therapeutic determination of OSCCs with satisfactory results (Kurokawa et al, 2005; Gueiros et al, 2011). Similarly, the histological risk (HR) model proposed by Brandwein-Gensler et al (2005) is based on the
Histopathological grading systems in oral cancer
I Sawazaki-Calone et al
756
evaluation of surgical specimens using three histopathological parameters: worst pattern of invasion (WPOI), lymphocytic host response (LHR), and perineural invasion (PNI). This model showed significant predictive power for recurrence and overall survival for OSCCs (BrandweinGensler et al, 2010; Vered et al, 2010a,b; Lindenblatt et al, 2012; Li et al, 2013; Sinha et al, 2015). Recently, Almangush et al (2015) introduced the BD model, which is based on two parameters: tumor budding (B) and depth of tumor invasion (D) in millimeters. Tumor budding, defined as the presence of a single cancer cell or small cluster of
ORIGINAL ARTICLE
The prognostic value of histopathological grading systems in oral squamous cell carcinomas I Sawazaki-Calone1,2, ALCA Rangel1, AG Bueno3, CF Morais4, HM Nagai5, RP Kunz6, RL Souza1, L Rutkauskis1, T Salo2,7,8, A Almangush7,8, RD Coletta2 1
Oral Pathology and Oral Medicine, Dentistry School, Western Paran a State University, Cascavel; 2Department of Oral Diagnosis, 3 Piracicaba Dental School, University of Campinas, Piracicaba; ANATOM Anatomic Pathology Laboratory, Cascavel; 4APC Anatomic Pathology Laboratory, Cascavel; 5UOPECCAN Cancer Hospital, Cascavel; 6Oncology Center of Cascavel (CEONC), Cascavel, Brazil; 7Department of Diagnostics and Oral Medicine, Institute of Dentistry and Oulu University Hospital, University of Oulu, Oulu; 8 Institute of Dentistry, University of Helsinki, Helsinki, Finland
OBJECTIVE: This study evaluated the association of four histopathological grading systems (WHO grading system, malignancy grading of the deep invasive margins (MG), histological risk (HR) model, and tumor budding and depth of invasion (BD) model) with clinicopathological parameters and outcome of 113 oral squamous cell carcinomas to identify their roles in prognosis. METHODS: Demographic and clinical features were obtained from patients’ records. Sections from all paraffin-embedded blocks were evaluated according to the four grading systems. Demographic and clinical associations were analyzed using chi-square test, and correlations between the grading systems were established with the Spearman’s rank correlation test. Survival curves were performed with Kaplan–Meier method, and multivariate analysis based on Cox proportional hazard model was calculated. RESULTS: Significant associations with survival were observed for WHO grading system and BD model in the univariate analysis, but only the BD model was significantly associated with disease outcome as an independent prognostic marker. Age, tumor size, and presence of regional metastasis were also independent markers of reduced survival. CONCLUSION: A significant association between the BD model and outcome of OSCC patients was observed, indicating this new histopathological grading system as a possible prognostic tool. Oral Diseases (2015) 21, 755–761
Correspondence: Iris Sawazaki-Calone, Oral Pathology and Oral Medicine, Dentistry School, Western Parana State University, Rua Universitaria, 2069, Jardim Universitario, CEP: 85819-110, Cascavel, PR, Brazil. Tel: +55 45 33063933, Fax: +55 45 33244566, E-mail: [email protected] Received 3 December 2014; revised 17 March 2015; accepted 20 March 2015
Keywords: oral squamous cell carcinoma; histopathological grading system; survival analysis; prognosis; oral cancer
Introduction Clinical staging of the disease based on TNM classification and location of the tumor are routinely the main criteria for prognostication and treatment of oral squamous cell carcinomas (OSCCs) (Dissanayaka et al, 2012). However, variations in the treatment response and prognosis are high for OSCCs, with some patients presenting tumors at the same site and same clinical stage having prolonged survival, while others may die of metastasis rapidly. In the view of those difficulties, it has been proposed that a detailed histopathological grading of the tumors with specific histopathological scoring systems could help the clinicians in the individualization of treatment and in prognostication of patients with OSCC (Anneroth et al, 1987; Bryne et al, 1992; Brandwein-Gensler et al, 2005; Almangush et al, 2015). The first histopathological grading system for OSCCs was developed by Broders in 1920 (Broders, 1920), which was later adopted for the World Health Organization (WHO) (Barnes et al, 2005). This system takes into account the degree of keratinization of the tumor, levels of cellular and nuclear pleomorphism, and presence of mitotic activity. Later on, many other histopathological grading systems have been proposed for OSCCs in the last century. The malignancy grading of the deep invasive margins (MG) proposed by Bryne and collaborators (Bryne et al, 1992) is a system that scores the degree of keratinization, nuclear polymorphism, pattern of invasion, and lymphoplasmacytic infiltration only in the most invasive areas. This grading system has been used for prognostication and therapeutic determination of OSCCs with satisfactory results (Kurokawa et al, 2005; Gueiros et al, 2011). Similarly, the histological risk (HR) model proposed by Brandwein-Gensler et al (2005) is based on the
Histopathological grading systems in oral cancer
I Sawazaki-Calone et al
756
evaluation of surgical specimens using three histopathological parameters: worst pattern of invasion (WPOI), lymphocytic host response (LHR), and perineural invasion (PNI). This model showed significant predictive power for recurrence and overall survival for OSCCs (BrandweinGensler et al, 2010; Vered et al, 2010a,b; Lindenblatt et al, 2012; Li et al, 2013; Sinha et al, 2015). Recently, Almangush et al (2015) introduced the BD model, which is based on two parameters: tumor budding (B) and depth of tumor invasion (D) in millimeters. Tumor budding, defined as the presence of a single cancer cell or small cluster of
