Malignancy Grading System Research Articles

Domain and Histopathology Adaptations–Based Classification for Malignancy Grading System

Accurate proliferation rate quantification can be used to devise an appropriate treatment for breast cancer. Pathologists use breast tissue biopsy glass slides stained with hematoxylin and eosin to obtain grading information. However, this manual evaluation may lead to high costs and be ineffective because diagnosis depends on the facility and the pathologists' insights and experiences. Convolutional neural network acts as a computer-based observer to improve clinicians' capacity in grading breast cancer. Therefore, this study proposes a novel scheme for automatic breast cancer malignancy grading from invasive ductal carcinoma. The proposed classifiers implement multistage transfer learning incorporating domain and histopathologic transformations. Domain adaptation using pretrained models, such as InceptionResNetV2, InceptionV3, NASNet-Large, ResNet50, ResNet101, VGG19, and Xception, was applied to classify the ×40 magnification BreaKHis data set into eight classes. Subsequently, InceptionV3 and Xception, which contain the domain and histopathology pretrained weights, were determined to be the best for this study and used to categorize the Databiox database into grades 1, 2, or 3. To provide a comprehensive report, this study offered a patchless automated grading system for magnification-dependent and magnification-independent classifications. With an overall accuracy (means ±SD) of 90.17%±3.08% to 97.67%±1.09% and an F1 score of 0.9013 to 0.9760 for magnification-dependent classification, the classifiers in this work achieved outstanding performance. The proposed approach could be used for breast cancer grading systems in clinical settings.

Malignant phyllodes tumors of the breast: the malignancy grading and associations with prognosis

This study aimed to correlate clinicopathological parameters with survival outcomes in a cohort of patients diagnosed with malignant phyllodes tumors (MPTs). We also analyzed the malignancy grade of MPTs and investigated the prognostic significance of the malignancy grading system. Clinicopathological parameters, malignancy grades, and clinical follow-up data of 188 women diagnosed with MPTs in a single-institution were analyzed. MPTs of the breast were grouped according to stromal atypia, stromal overgrowth, mitotic count, tumor differentiation, and necrosis. A Fleiss' kappa statistic was calculated to test the agreement between the pathologists for the grading of MPTs. Disease-free survival (DFS), distant metastasis-free survival (DMFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Cox regression was carried out to identify factors predictive of locoregional recurrence (LRR), distant metastasis (DM) and death. A total of 188 MPTs were classified according to the malignancy grading system: 88 (46.8%) as low grade, 77 (41%) as an intermediate grade, and 23 (12.2%) as high grade. Excellent agreement between pathologists for the grading of MPTs (Fleiss' kappa 0.807). In our study population, the occurrence of DM and death were associated with the malignancy grade of MPTs (P < 0.001). Based on the DFS curves, the presence of heterologous elements (P = 0.025) and younger age (P = 0.014) were independent prognostic indicators. Additionally, the malignancy grade retained independent prognostic significance for predicting DMFS and OS (P < 0.001 and P = 0.009). Higher malignancy grade, presence of heterologous elements, younger age, larger tumor size, and recent rapid tumor growth are poor prognostic factors for MPTs of the breast. The malignancy grading system may be generalized in the future.

Prognostic implications of malignancy grading of invasive fronts of oral squamous cell carcinoma.

Invasive front malignancy grading system in oral squamous cell carcinoma (OSCC) introduced by Bryne et al. is reported to be of prognostic significance in a number of studies conducted in Western countries. The aim of this study was to evaluate the prognostic significance of the modified Bryne's malignancy grading system and to compare it with the World Health Organization (WHO) grading system in the Indian population. The records of 50 patients diagnosed with primary OSCC were evaluated. Only large surgically resected specimens that had deep invasive fronts in the cut sections were selected. All hematoxylin and eosin-stained slides were analyzed by two grading systems: the WHO grading system and the Bryne's malignancy grading of the deep invasive fronts of OSCCs. Histopathologic grading in the invasive sites had highly significant prognostic value and had significant correlation with overall survival rate. The Kaplan-Meier survival curves showed that five years following therapy, the proportion of cases surviving with Bryne's scores lower or equal to 12 was 60.6% compared to only 17.6% for those with scores greater than 12. The drop in the survival curve of the patients with Bryne's scores greater than 12 was much steeper toward the end of the two years (nearly 16 months). In WHO Grades I and II, the survival rate was 48.9% and in Grade III, it was Nil. The histologically invasive areas may be the only prognostic indicator for the clinical behavior of OSCC and can be used to predict overall survival in patients.

Application of EGFR, ki 67 and GFAP as a panel for the diagnosis and grading of astrocytomas

Background: Astrocytic tumors are the most common primary central nervous system tumors. WHO grading scheme is based on the presence or absence of the following four histological parameters using haematoxylin and eosin (H&E) staining: cellular atypia (WHO grade II), mitotic figures (WHO grade III), endothelial proliferation, and/or necrosis (WHO grade IV). Immunohistochemistry (IHC) has become an essential tool in diagnosis of brain tumors and helps in predicting the prognosis of certain brain including astrocytomas. Aim: Study the immunohistochemical expressions of (Epidermal growth factor receptor (EGFR), Ki67 and Glial fibrillary acidic protein (GFAP)) in different grades of astrocytomas. Materials and Methods: This study included 44 cases of astrocytomas classified as: 3 pilocytic astrocytomas, 6 diffuse low grade astrocytomas, 15 anaplastic astrocytomas and 20 glioblastoma multiforms. Immunohistochemical staining of all cases using EGFR, Ki67 and GFAP was done. Results: EGFR showed positive membranous and cytoplasmic expression in 33 (75%) cases, GFAP positive staining was detected in 38 (86.4%) of studied cases while all astrocytomas of different grades showed ki67 positivity with variable degrees with the mean ± SEM of Ki67 LI 17.76% ± 2.46. There was statistically significant relation between EGFR, Ki 67 and GFAP expression and tumor grade. Conclusions: EGFR, Ki 67 and GFAP should be used in combination as a panel side by side with established histological criteria of malignancy and WHO grading system for accurate diagnosis and grading of astrocytic tumors.

Computed Tomographic and Histopathological Characteristics of 13 Equine and 10 Feline Oral and Sinonasal Squamous Cell Carcinomas

Squamous cell carcinoma (SCC) is the most common equine sinonasal and feline oral tumour. This study aimed to describe the computed tomographic and histopathological characteristics of equine and feline SCC. Thirteen horses and 10 cats that had been histopathologically diagnosed with oral or sinonasal SCC and had undergone computed tomography (CT) of the head were retrospectively included in the study. CT characteristics of the mass and involved structures were noted. Histological examinations were evaluated according to a human malignancy grading system for oral SCC, which considered four grades of increasing aggressiveness. In horses, the masses were at the levels of the paranasal sinuses (n = 8), mandible (n = 3), tongue (n = 1), and nasal cavity (n = 1). In cats, the masses were at the levels of the maxilla (n = 4), mandible (n = 3), tongue (n = 1), and buccal region (n = 1) and were diffusely distributed (facial and cranial bones; n = 1). Masses in the equine paranasal sinuses showed only mild, solid/laminar, periosteal reactions with variable cortical destruction. However, maxillary lesions in cats showed severe cortical destruction and irregular, amorphous/pumice stone-like, periosteal reactions. CT revealed different SCC phenotypes that were unrelated to the histological grade. For morphologic parameters of the tumour cell population, a variability for the degree of keratinization and number of mitotic cells was noted in horses and cats. Concerning the tumour-host relationship a marked, extensive and deep invasion into the bone in the majority of horses and cats was seen. Most cases in both the horses and cats were categorized as histological grade III (n = 8); four horses and one cat were categorized as grade IV, and one horse and one cat were categorized as grade II. In this study, we examined the diagnostic images and corresponding applied human histopathological grading of SCC to further elucidate the correlations between pathology and oral and sinonasal SCC imaging in horses and cats.

Staging more important than grading? Evaluation of malignancy grading, depth of invasion, and resection margins in oral squamous cell carcinoma

ObjectivesThe present study evaluated the predictive value of staging and grading parameters concerning the presence of lymph-node metastases, overall survival (OS), and relapse-free survival (RFS) of patients with oral squamous cell carcinoma (OSCC).Materials and methodsHE-stains of 135 surgically treated (R0) primary OSCCs were analyzed using a both microscopic and software-based approach. Depth of invasion (DOI) and resection margins (RM) were measured, and each case was graded according to the malignancy grading system as described by Anneroth et al. and Bryne et al. on two different sites of the tumor (surface and invasion front; TS and IF).ResultsParameters that could be identified as significant predictors of OS and RFS were UICC cancer stage (p = 0.009 and p = 0.012); pT-stage as defined in the 7th edition (p = 0.029 and 0.015) and, after restaging using DOI, 8th edition (p = 0.023 and p = 0.005) of the TNM classification of malignant tumors; the presence of lymphonodular metastases (LM) (p = 0.004 and p = 0.011); degree of keratinization (p = 0.029 and p = 0.042); and pattern of growth (p = 0.029 and p = 0.024) at the TS after applying a binary scale for both parameters. Also, when directly comparing the most extreme subgroups (scores 1 and 4) of lymphoplasmacytic infiltration at the IF, there was a significant difference in OS (p = 0.046) and RFS (p = 0.005). Invasion of blood vessels (p = 0.013) and perineural invasion (p = 0.023) were significantly associated with a lower OS. Age lower than 60 years (univariate p = 0.029, multivariate p = 0.031), infiltration of lymphatic vessels (p = 0.003), infiltration of nerves (p = 0.010), pT-stage (8th edition) (p = 0.014), degree of keratinization at the IF (p = 0.033), and nuclear polymorphism at the IF (p = 0.043) after conversion to a binary scale were found to be significant prognostic parameters regarding the presence of LM. DOI evolved as a significant predictor for OS (p = 0.006), RFS (p = 0.003), and LM (p = 0.032) in metric and grouped analysis.ConclusionsThe current evaluation revealed depth of invasion as strongest histologic predictor of metastatic tumor growth, overall survival, and relapse-free survival in OSCC, confirming the current adaption of the T-classification. Other distinct histologic grading parameters investigated during this study can give valuable indications of a tumor’s potential aggressiveness, but the exact site, mode, and procedure need further exploration.Clinical relevanceIntegrating measurement of DOI also into the pretherapeutic staging process could aid in treatment planning.

Twist and E-cadherin deregulation might predict poor prognosis in lower lip squamous cell carcinoma

The aim of this study was to evaluate the expression of Twist and E-cadherin in lower lip squamous cell carcinoma (LLSCC) and their association with clinicopathologic parameters. Fifty-nine cases of LLSCC were analyzed by applying immunohistochemistry techniques in a semiquantitative manner. The systems proposed by Bryne etal., Brandwein-Gensler etal., and Almangush etal. were applied for analysis of the histopathologic malignancy grading system. Higher E-cadherin expression (general and membrane) was observed in cases presenting with disease-free survival after 5years of follow-up (P < .05). Higher Twist expression was observed in lesions classified as being in advanced stages, displaying recurrence, and having a high degree of malignancy. A significant negative correlation was detected between cytoplasmic Twist expression and membrane E-cadherin expression (P = .028). A statistically significant relationship was detected between high total Twist expression in tumors classified as high risk by Brandwein-Gensler etal., and no significant difference was observed among total, membrane, and cytoplasmic E-cadherin expressions in LLSCC cases and the 3 applied grading systems (P > .05). The results of the present study suggest the potential involvement of Twist and E-cadherin in the modulation of events related to worse prognoses in LLSCC cases.

Malignancy grading of invasive fronts of oral squamous cell carcinomas

Background: Clinical stage and pathology grading have consistently failed to predict survival in patients diagnosed with oral squamous cell carcinoma (OSCC). There is a need to develop a grading system that could have a predictive value in assessing the prognosis of patients with OSCC. The aim was to evaluate the prognostic significance of several parameters of the modified Bryne’s malignancy grading system. Methods: Malignancy grading of invasive fronts of 60 OSCCs from Sri Lankan subjects was undertaken using Bryne’s criteria. Results: Of the five morphological features assessed at the invasive fronts of the tumours, the range of scores derived for keratinization was low, and the host response in the stromal tissue was marked compared with reported series from European countries. There were no tumours scoring a malignancy grading under 9, regarded as tumours with a ‘good prognosis’. In logistic regression analysis among patient factors, age had a positive association on survival, and among tumour factors, the malignancy grading was significantly predictive of overall survival. Conclusions: Bryne’s malignancy grading is predictive of overall survival in patients with OSCCs.

Immunohistochemical expression of p53 and its clinicopathological correlation with modified Anneroth's histological grading system.

Introduction and Objectives:Oral squamous cell carcinoma (OSCC) is an epithelial neoplasm generally beginning as focal overgrowth of altered stem cells near the basement membrane, moving upward and laterally, replacing the normal epithelium. Histopathological grading has been used for many decades in an attempt to predict the clinical behavior of oral squamous cell carcinoma. In the present study, Forty biopsies were studied for histological grading and p53 expression. The p53 expression was studied in relation to clinical parameters such as age, sex of patient and site of tumors. Relation between histological grade of malignancy and p53 protein expression was analysed. All cases were classified according to Anneroth's histological malignancy grading system (1987).Materials and Methods:40 cases of OSCC were assessed for clinical parameters, Anneroth's histological grading and immunohistochemically stained with p53 protien.Statistical Analysis:The results obtained were analyzed using Spearman's Co-relation.Observations and Results:The positive expression of p53 was found in 62% of carcinomas studied. Positivity of p53 showed correlation with histological grade of malignancy and with individual parameters like degree of keratinization, nuclear polymorphism, number of mitoses and lymphoplasmacytic infiltration while showed a negative correlation with pattern of invasion.Conclusion:Our study showed a significant correlation between parameters of tumor cell population, lymphoplasmacytic infiltration and p53 expression. A significant association between high grade of malignancy and p53 overexpression and insignificant correlation of p53 with age, sex of the patient and site of the tumor was found.

Prognostic efficacy of nuclear morphometry at invasive front of oral squamous cell carcinoma: an image analysis microscopic study.

Background. Oral cancer is revisited on a pathologist perspective with advanced imaging technique. Objective. The present study assessed the new malignancy grading system at tumor proper (TP) and Bryne's grading system at invasive tumor front (ITF), morphometric features using software, to clarify their associations with prognosis of oral cancers. Methods. Histologically confirmed oral squamous cell carcinoma (OSCC) with 5-year follow-up was assessed morphometrically using image analysis at TP and ITF, correlated with the prognosis of patient. Results. On comparison of grading systems, a moderate agreement between both (Bryne and Anneroth) was seen. Among all histological parameters, we noted inverse correlation between degree of mitosis at invasive front and decrease in lymphoplasmacytic infiltrate at ITF with increase rate of recurrence and event of death. An increase in nuclear area, diameter, and perimeter along with decrease circularity in advancing OSCC was seen. Correlation of parameters showed higher values for maximum nuclear diameter, perimeter, and circularity at TP and ITF with recurrence. Conclusion. This study, while limited in sample size, concluded that a combined assessment of clinical TNM staging, histopathological grading system {excluding the parameter “mitotic activity” (due to its inverse relation)}, and nuclear morphometry at the ITF are better prognosticators. This combination proved to be an accurate predictive factor in eliciting the varied molecular characteristics of tumor heterogeneity.

New malignant grading system for hepatocellular carcinoma using the Sonazoid contrast agent for ultrasonography

The ultrasonography contrast agent Sonazoid provides parenchyma-specific contrast imaging (Kupffer imaging) based on its accumulation in Kupffer cells. This agent also facilitates imaging of the fine vascular architecture in tumors through maximum intensity projection (MIP). We examined the clinical utility of the malignancy grading system for hepatocellular carcinoma (HCC) using a combination of 2 different contrast-enhanced ultrasonography images. We studied 121 histologically confirmed cases of HCC (well-differentiated, 45; moderately differentiated, 70; poorly differentiated, 6). The results of Kupffer imaging were classified as (1) iso-echoic pattern or (2) hypo-echoic pattern. The MIP patterns produced were classified into one of the following categories: fine, tumor vessels were not clearly visualized and only fine vessels were visualized; vascular, tumor vessels were visualized clearly; irregular, tumor vessels were thick and irregular. Based on the combined assessment of Kupffer imaging and the MIP pattern, the samples were classified into 4 grades: Grade 1 (iso-fine/vascular), Grade 2 (hypo-fine), Grade 3 (hypo-vascular), and Grade 4 (hypo-irregular). The distribution of moderately and poorly differentiated HCCs was as follows: Grade 1, 4% (1/24); Grade 2, 52% (15/29); Grade 3, 85% (44/52); and Grade 4, 100% (16/16). The grading system also predicted portal vein invasion in 72 resected HCCs: Grade 1, 0% (0/4); Grade 2, 13% (1/8); Grade 3, 23% (11/48); and Grade 4, 67% (8/12). This new malignant grading system is useful for estimation of histological differentiation and portal vein invasion of HCC.

Malignancy grading is no better than conventional histopathological grading in small squamous cell carcinoma of tongue and floor of mouth: retrospective study in 128 patients

There is an ongoing debate about the predictive value of histopathological parameters in oral cancer. In the past decades, the emphasis was on the possible added value of the so-called malignancy grading system. In a retrospective study on 128 previously untreated patients with a T1 or T2 squamous cell carcinoma of the tongue and the floor of the mouth, the value of the classical Broders' grading system and the malignancy grading system were compared with regard to various outcome measures such as regional metastasis, local recurrence and 5-year survival. The results show that neither of the histological grading systems has a strong predictive value and that none is superior to the other.

Matrix Metalloproteinase-19 is a Predictive Marker for Tumor Invasiveness in Patients with Oropharyngeal Squamous Cell Carcinoma

To evaluate the expression of matrix metalloproteinase-19 (MMP-19) in oropharyngeal squamous cell carcinoma along with its association with structural features of invasiveness. To investigate whether MMP-19 expression correlates with lymphatic or systemic metastasis and prognosis in patients who have received definitive radiotherapy. The histological evaluation of the invasive front was based on Bryne's malignancy grading system. We correlated the immunohistochemical expression pattern with morphological parameters which characterize tumor invasiveness such as keratinization, nuclear polymorphism, invasion pattern, and the host inflammatory response. Local immunoreactivity for MMP-19 was positively correlated with tumor invasiveness as reflected in its structural characteristics and the degree of nuclear polymorphism, and negatively correlated with the inflammatory response of the host. No correlation existed between MMP-19 expression and clinicopathological features (TNM stage, grade of differentiation) or a patient''s outcome and prognosis. This latter finding probably reflects the unique change for MMPs from high immunoreactivity within healthy tissue areas and non-invasive tumor parts, through absence in the least invasive neoplastic regions, to strong re-expression at a highly invasive front of the same tumor. Our findings indicate that MMP-19 can be used as a marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma.

Matrix metalloproteinase-19 is a predictive marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma.

To evaluate the expression of matrix metalloproteinase-19 (MMP-19) in oropharyngeal squamous cell carcinoma along with its association with structural features of invasiveness. To investigate whether MMP-19 expression correlates with lymphatic or systemic metastasis and prognosis in patients who have received definitive radiotherapy. The histological evaluation of the invasive front was based on Brynes malignancy grading system. We correlated the immunohistochemical expression pattern with morphological parameters which characterize tumor invasiveness such as keratinization, nuclear polymorphism, invasion pattern, and the host inflammatory response. Local immunoreactivity for MMP-19 was positively correlated with tumor invasiveness as reflected in its structural characteristics and the degree of nuclear polymorphism, and negatively correlated with the inflammatory response of the host. No correlation existed between MMP-19 expression and clinicopathological features (TNM stage, grade of differentiation) or a patient''s outcome and prognosis. This latter finding probably reflects the unique change for MMPs from high immunoreactivity within healthy tissue areas and non-invasive tumor parts, through absence in the least invasive neoplastic regions, to strong re-expression at a highly invasive front of the same tumor. Our findings indicate that MMP-19 can be used as a marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma.

Análise da imunoexpressão do PCNA e p53 em carcinoma de células escamosas oral: correlação com a gradação histológica de malignidade e características clínicas

OBJETIVO: Analisar a imunoexpressão das proteínas PCNA e p53 em carcinoma de células escamosas oral (CCEO) vislumbrando verificar uma possível correlação entre o escore de malignidade e os dados clínicos dos pacientes. MÉTODOS: Selecionou-se 14 casos de CCEO e classificando-os de acordo com uma adaptação do sistema de gradação histológica de malignidade proposto por Anneroth, Batsakis, Luna, enquadrando-se 7 casos como baixo escore de malignidade (Grupo I) e 7 casos como alto escore (Grupo II). As informações dos pacientes foram coletadas através de fichas clínicas e os dados tabulados. Realizou-se, então, o estudo imuno-histoquímico utilizando anticorpos monoclonais anti-PCNA e anti-p53, obtendo-se o índice de positividade (IP) em cada caso. RESULTADOS: Identificou-se um IP médio ao PCNA de 56,0% no Grupo I e 83,8% no Grupo II. Com relação à p53 o IP médio no Grupo I e no Grupo II correspondeu, respectivamente, a 41,2% e 41,4%. A análise estatística demonstrou correlação significativa entre o índice de células PCNA positivas e o escore de malignidade. Nenhuma outra correlação foi observada. CONCLUSÕES: O maior número de células PCNA positivas correlacionou-se com elevado escore de malignidade em CCEOs, sugerindo maior atividade proliferativa nestas lesões, entretanto, tal correlação não se estabeleceu quando da análise da imunoexpressão da p53.

Clinical-pathological parameters in squamous cell carcinoma of the tongue.

The correlation between TNM classification and histological scores of malignancy, and the correlation of these parameters with the prognosis was evaluated in 16 cases of squamous cell carcinoma of the tongue. The cases were selected from the files of "Dr. Luiz Antônio" Cancer Hospital, Natal, RN, Brazil. After analysis of the patients' records, the data concerning TNM classification and prognosis (in a 5-year-follow-up) were obtained. All cases were classified according to the histological malignancy grading system proposed by Anneroth et al. [Scand Dent Res 1987;95:229-249]. There was no correlation (r = 0.3083) between TNM classification and histological scores of malignancy. There was significant correlation (r = 0.7206) between TNM classification and prognosis, but there was no correlation between the histological scores of malignancy and the prognosis. It was concluded that TNM classification is an important prognostic indicator of squamous cell carcinoma of the tongue.

Collagen type I expression in squamous cell carcinoma of the oral cavity

An analysis of the extracellular matrix at the invasive front of squamous cell carcinoma of the oral cavity may improve the understanding of tumour cell matrix interactions during malignancy growth. Alterations in collagen I expression may influence cellular invasion and metastasis. In this work, 23 cases of squamous cell carcinoma were submitted to the Anneroth's malignancy grading system. H. E. and sirius red staining were used. Immuno-histochemical expression of collagen type I protein was observed in different malignancy scores. As a result, it was observed that the extracellular matrix in squamous cell carcinoma of the oral cavity shows different patterns of collagen I expression in low and high scores of malignancy.

Predictive value of malignancy grading systems, DNA content, p53, and angiogenesis for stage I tongue carcinomas.

AIM: To assess the clinical value of malignancy grading systems compared with nuclear DNA content, protein p53, and angiogenesis for predicting recurrence of stage I (UICC, 1987) tongue carcinomas. METHODS:...

Is the invasive front of an oral carcinoma the most important area for prognostication?

The prognosis for patients with oral squamous cell carcinomas is difficult to predict. There is therefore a great need for more reliable prognostic markers which will be of help in the treatment decisions. In this review I present a hypothesis which suggests that molecular and morphological characteristics at the invasive front area of various carcinomas may reflect tumour prognosis better than other parts of the tumour. It is now known that several molecular events of importance for tumour spread like gains and losses of adhesion molecules, secretion of proteolytic enzymes, increased cell proliferation and initiation of angiogenesis occur at the tumour-host interface (invasive front). Consequently, our group has recently developed a simple morphological malignancy grading system that restricts the evaluation to the deep invasive front area of the tumour. Several studies have shown that this system is a significantly better predictor of prognosis than traditionally used morphological systems. All studies performed so far show that invasive front grading is a valuable supplement to clinical staging, suggesting that it should be introduced into the clinic.

P53 in biopsies of oral squamous cell carcinoma. A comparative study with a malignancy grading system

The relationship between the histological grading of malignancy and p53 protein expression was studied in 40 biopsies of oral squamous cell carcinomas. An immunohistochemical analysis was carried out using the streptavidin method preceded by a treatment with citric acid in a microwave oven. All cases were classified according to the histological malignancy grading system proposed by Anneroth et al. (Scandinavian Journal of Dental Research 1987, 95, 229-249). The expression of p53 was found in 62.5% of the carcinomas studied. Positivity of p53 staining showed a correlation with the histological grade of malignancy and with the degree of keratinisation, nuclear polymorphism and number of mitoses.