Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas

Abstract

Background: This study aimed to compare the histological and immunohistochemical characteristics of ameloblastomas (AM) and ameloblastic carcinomas (AC).

Material and methods: Fifteen cases of AM and 9 AC were submitted to hematoxilin and eosin (H&E) and immunohistochemical analysis with the following antibodies: cytokeratins 5,7,8,14 and 19, Ki-67, p53, p63 and the cellular adhesion molecules CD138 (Syndecan-1), E-cadherin and β-catenin. The mean score of the expression of Ki-67 and p53 labelling index (LIs) were compared between the groups using the t test. A value of p<0.05 was considered to be statistically significant.

Results: All cases were positive for CKs 5, 14 and 19, but negative for CKs 7 and 8. CKs 5 and 19 were positive mainly in the central regions of the ameloblastic islands, while the expression in AC was variable in intensity and localization. CK14 was also variably expressed in both AM and AC. Ki-67 (P=.001) and p53 (P=.004) immunoexpression was higher in AC. All cases were positive for p63, but values were higher in AC. CD138 was mainly expressed in peripheral cells of AM, with a weak positivity in the central areas, while it was positive in most areas of ACs, except in less differentiated regions, where expression was decreased or lost. E-cadherin and β-catenin were weakly positive in both AM and AC.

Conclusions: These results shows that Ki-67, p53 and p63 expression was higher in AC as compared to AM, suggesting that these markers can be useful when considering diagnosis of malignancy, and perhaps could play a role in malignant transformation of AM. Pattern of expression of CKs 5 and 19 in AC were different to those found in AM, suggesting genetic alterations of these proteins in malignant cells. It was confirmed that CK19 is a good marker for benign odontogenic tumors, such as AM, but it is variably expressed in malignant cases.

Figure 1

Main immunohistochemical features in ameloblastoma: a. Ameloblastoma showing the nuclei of a few cells of the basal and suprabasal layers positive for Ki-67 (200X), b. Nuclear expression of p53 in AM, positive cells are evident, but the intensity of the staining is weak- arrows (200X), c. p63 immunostaining in ameloblastomas, showing epithelial islands intensely positive mainly in the peripheral cells, but many of the central cells also expressed this marker (200X), d. The central areas of the islands/cords were strongly positive for CK5, while the expression was weaker or negative on the peripheral columnar cells (200X), e. Follicular islands showing stronger expression in the central areas, but the basal layer was also positive. Arrow shows squamous metaplasia with cells weakly positive (200X), f. CK19 immunostaining in ameloblastoma, showing central cells intensely positive, with weak or negative expression in the basal and suprabasal layers (400X), g. Higher magnification of an epithelial island illustrating positiveness of CD138 mainly in the basal and suprabasal layers. Arrow shows squamous metaplasia, with peripheral cells exhibiting strong positivity, with the more central squamous cells loosening expression (400X), h. Central areas of an epithelial ameloblastic sheet showing positivity in cells presenting characteristics of squamous metaplasia (400X), i. Case of AM showing strong positiveness for β-catenin mainly in the peripheral columnar cells, loosing expression in some central cells. This strong staining was not common, as in most of the cases the labeling with β-catenin was weak or practically negative (200X).

Figure 2

Most cases of ameloblastic carcinoma involved the posterior mandible. This figure illustrates two unusual cases, one involving the anterior mandible and the other the left maxilla, a. Panoramic radiography showing irregular radiolucent lesion involving the anterior mandible causing tooth displacement, mobility and loss, b. AC of left maxilla affecting the alveolar ridge and extending into the palate. The perforation in the mucosa corresponds to a recent tooth extraction, c. Radiograph of the same case showing radiolucent image involving the left maxillary sinus and adjacent areas, including floor of the orbit.

Figure 3

Histological features of ameloblastic carcinoma, a. Epithelial islands with artefactual empty central spaces showing a follicular pattern, resembling an ameloblastic epithelium with columnar peripheral cells. The stroma is highly collagenized (H&E, 400X), b. Sheets of malignant epithelial cells showing a peripheral layer formed by columnar cells, with ameloblastic characteristics, including reversal nuclear polarization. Cellular pleomorphism and atypical mitosis are evident (H&E, 400X), c. Sheets of malignant epithelial cells showing a central area of necrosis (H&E, 200X). d, Islands of well-defined malignant epithelium, with flattened peripheral cells separated by collagenized stroma. The islands are frequently separated from the adjacent stroma, suggesting a poor adherence of epithelium/stroma adherence interface (H&E, 200X).

Figure 4

Main immunohistochemical features in ameloblastic carcinoma: a. Epithelial cells showing strong and high expression of Ki-67 in most of the cells (200X), b. Nuclear expression of p53 in AC, positive cells are evident, but the intensity of the staining is weak (200X), c. p63 immunostaining in ameloblastic carcinoma, with most of the nuclei strongly positive (200X), d. Strong and homogenous expression of CK5 in AC, both in the central and peripheral cells of the epithelial islands, with loss of expression in focal areas (200X), e. Neoplastic islands illustrating strong expression for CK14 in most cells, but loss of staining or weak expression in focal regions (200X), f. CK19 staining in ameloblastic carcinoma, showing strongly positive cells permeated by negative cells in both peripheral and central areas (200X), g. epithelial malignant sheet showing most cells with strong positivity for CD138 (400X), h. Case of AC strongly expressing E-cadherin in most of the cells; nevertheless, expression was variable in most cases, and some were negative (200X), i. Case of AC showing strong expression of β-catenin. In most cases it was weakly positive or negative (200X).