Immunohistochemical Study of Differential Expressions of Cytokeratin-13, -14, -17 and p53 in Epithelial Dysplasia and Carcinoma of the Tongue

Abstract

In cancers of the oral cavity, high histological malignancy grade is associated with higher risk of cervical lymph nodes, lung and bone metastases, which have great impact on the prognosis. Furthermore, early detection of these cancers is desirable so that treatment can aim at conserving oral functions and improving prognosis. It is known that several percent of leukoplakia that develop in the tongue become cancerous. Leukoplakia is a clinical diagnostic term, and histopathologically most cases show hyperkeratosis with epithelial dysplasia or hyperkeratosis without epithelial dysplasia. On the other hand, difficulties in histopathological diagnosis of severe epithelial dysplasia and carcinoma in situ are often encountered. In recent years, immunohistochemical staining of cytokeratins (CK), p53 and Ki-67 for precancerous lesions and squamous cell carcinoma (SCC) of the oral cavity has been reported. However, few reports have applied a combination of several immunohistochemical stainings to diagnosis. In the present study, with the objective to achieve a higher precision in histopathological diagnosis, we conducted and compared the immunohistochemical stainings of CK13, CK17, CK14 and p53 in 10 cases each of hyperkeratosis without epithelial dysplasia, hyperkeratosis with epithelial dysplasia, carcinoma in situ, and SCC in the tongue. The following results were obtained. CK13 was positive in all 10 cases of hyperkeratosis without epithelial dysplasia, and negative in all cases of hyperkeratosis with epithelial dysplasia, carcinoma in situ, and SCC. CK17 was negative in all 10 cases of hyperkeratosis without epithelial dysplasia, and was positive in all 10 cases of hyperkeratosis with epithelial dysplasia as well as 10 cases of carcinoma in situ and 9 of 10 cases of SCC. CK14 was negative or positive only in the basal cell layer or a few rows of cells in spinous layer adjacent to the basal cell layer in cases of hyperkeratosis without epithelial dysplasia, but was positive in all the epithelial layers in all 10 cases of hyperkeratosis with epithelial dysplasia, and also positive in the tumor in all 10 cases each of carcinoma in situ and SCC. For p53, positive reaction was observed in some cells of the basal cell layer in 2 of 10 cases of hyperkeratosis without epithelial dysplasia, while high positive rates were found in hyperkeratosis with epithelial dysplasia (10 of 10 cases) and SCC (9 of 10 cases). On the other hand, only 5 of 10 cases of carcinoma in situ were positive for p53. In conclusion, although the histopathological diagnosis of epithelial dysplasia and carcinoma in situ is based on hematoxylin-eosin stained sections, immunostaining and evaluation of CK13, CK17, CK14 and p53 are useful as an adjunct to histopathological diagnosis.

Cytokeratin 13, Cytokeratin 17, Ki-67 and p53 Expression in Upper Layers of Epithelial Dysplasia Surrounding Tongue Squamous Cell Carcinoma

“…Malignance marker p53 is a protein encoded by the TP53 tumor-suppressor gene, and is associated with apoptosis, the cell cycle, and genetic homeostasis 13) . Immunohistochemical expression of p53 is also mainly observed in the basal and parabasal cell layers, and its levels are increase depending on the severity of oral epithelial dysplasia, similarly to Ki-67 levels 15,16) .…”

Multivariate analyses of Ki‐67, cytokeratin 13 and cytokeratin 17 in diagnosis and prognosis of oral precancerous lesions

“…Many studies have identified molecular markers for the pathological diagnosis or prognosis of oral atypical epithelium (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). For example, immunohistochemical detection of the proliferation marker Ki-67 and the squamous cell-differentiation markers cytokeratin 13 (CK13) and CK17 were reported to be useful for differentiating between OPL and reactive atypical epithelium (2,6,9,10,(15)(16)(17)(18)(19)(20)(21). CK13 is usually expressed in the normal oral epithelium but not in OPL, whereas CK17 is expressed in OPL, but not the normal oral epithelium.…”

“…Overall, studies assessing the diagnostic or prognostic potential of molecular markers are limited. In these studies (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), the reliability of immunohistochemical scoring methods, the rationale for selecting certain cutoff points for defining sensitivity or specificity, and ascertainment of the independent contributory role(s) of each molecular marker to diagnosis or prognosis have been controversial. In this study, we sought to assess the diagnostic values of Ki-67, CK13, and CK17 for high-grade dysplasia by using logistic regression analyses.…”

Immunohistochemical findings and differential diagnosis of papillary-type cutaneous verrucous carcinoma of the neck: A case report

“…However, the hypothesis that numerous immunohistochemical analyses are useful in the diagnosis of papillary-type cutaneous VC was confuted by the current study. CK13, 8 and 18 are reported to be useful markers in the diagnosis of squamous cell carcinoma in the head and neck region (13,15), and CK8 and 18 appear to be associated with the invasion and metastasis of squamous cell carcinoma (16). However, these CKs stained negatively in the neoplastic and surrounding healthy epidermal tissue of the present lesion, and, therefore, were not useful in the differential diagnosis of the present case.…”