Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections

Abstract

Immunohistochemical loss of keratin (K)13 is one of the most valuable diagnostic criteria for discriminating carcinoma in situ (CIS) from non-malignancies in the oral mucosa while K13 is stably immunolocalized in the prickle cells of normal oral epithelium. To elucidate the molecular mechanism for the loss of K13, we compared the immunohistochemical profiles for K13 and K16 which is not expressed in normal epithelia, but instead enhanced in CIS, with their mRNA levels by in-situ hybridization in formalin-fixed paraffin sections prepared from 23 CIS cases of the tongue, which were surgically removed. Reverse transcriptase-PCR was also performed using RNA samples extracted from laser-microdissected epithelial fragments of the serial paraffin sections in seven of the cases. Although more enhanced expression levels for K16 were confirmed at both the protein and gene levels in CIS in these seven cases, the loss of K13 was associated with repressed mRNA levels in four cases, but not in the other three cases. The results suggest that the loss of K13 is partly due to its gene repression, but may also be due to some unknown post-translational events.

Evaluation of Superficial Oral Squamous Cell Malignancy Based on Morphometry and Immunoexpression of Cytokeratin 13 and Cytokeratin 17

“…Ohkura et al [18] reported that CK13 expression levels were lower in oral squamous cell carcinoma and severe epithelial dysplasia than in mild and moderate epithelial dysplasia, and several additional studies have since reported that CK13 expression decreases with increasing severity of epithelial dysplasia [12,13,19]. The mechanism of CK13 expression has not yet been fully elucidated, but Ida-Yonemochi et al [15] suggested that K13 might be posttranscriptionally regulated by repression of gene translation in oral keratinocytes. A similar relationship between CK13 expression and malignant potential has been reported in uterine cervical [23] and oesophageal epithelia [24].…”

“…A multitude of studies have found significant relationships between malignancy and the expression levels of CK13 and CK17, indicating that combined assessment of CK13 and CK17 expression status might be a highly reliable diagnostic test to identify malignant transformation of oral epithelial dysplasia and oral squamous cell carcinoma [11,12,13,14,15,16,17,18,19,20]. However, it was previously unknown whether the expression status of CK13 or CK17 correlates with the morphological signs of atypia in superficial oral squamous cells collected by oral exfoliative cytology.…”

“…Recent molecular and immunohistochemical studies have shown that cytokeratin 13 (CK13) and cytokeratin 17 (CK17) are useful biomarkers for oral malignant lesions and are valuable adjuncts to conventional histological evaluation [11,12,13,14,15,16,17,18,19,20]. …”

Impact of Daily Using Alcohol-containing Mouthwashes on Tongue, Cementum, and Enamel Surface; In vitro and In vivo Studies

“…Recent research shows that long-term use of alcohol-containing mouthwashes may lead to rapid atrophy of different types of papillae, disturbance of metabolic enzymes in oral cavity, and vascular insufficiency [25]. In addition, evidence indicates that regular alcohol consumption induces sever changes of oral mucosal cells due to substantial alteration of epidermal growth factor receptors (EGFR) and loss of keratin 13 proteins [26][27][28]. This clearly implies that alcohol showed a higher capacity to eliminate the lipid components of the cell barriers in the oral cavity, which surround the cellular granules at the epithelial spinous layer [6].…”

Heterogeneous and abnormal localization of desmosomal proteins in oral intraepithelial neoplasms

“…Cytokeratin is a helpful diagnostic marker for evaluation of cellular differentiation in tumors (4), and cytokeratins 13 and 19 in particular are useful for diagnosis or biological characterization of oral precancerous lesions or carcinomas in situ in squamous epithelium (5,6). However, the distribution of cytokeratin differs among the various types of oral mucosa, such as those overlying the tongue and the gingiva, and thus shows a degree of heterogeneity.…”