Down-regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia: a clue for histopathogenesis

• Published in: Histopathology Vol. 58; no. 4; pp. 531 - 542
• Main Authors: Sakamoto, Kei, Aragaki, Tadanobu, Morita, Kei-ichi, Kawachi, Hiroshi, Kayamori, Kou, Nakanishi, Shoichi, Omura, Ken, Miki, Yoshio, Okada, Norihiko, Katsube, Ken-ichi, Takizawa, Toichiro, Yamaguchi, Akira
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2011; Blackwell
• Subjects: Biological and medical sciences; Biopsy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cell Line; Cloning, Molecular; cytokeratin; Dermatology; Down-Regulation - genetics; Epithelial Cells - metabolism; Epithelial Cells - pathology; epithelial dysplasia; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); keratin; keratin 13; keratin 4; Keratin-13 - genetics; Keratin-13 - metabolism; Keratin-4 - genetics; Keratin-4 - metabolism; Male; Medical sciences; Mouth Mucosa - pathology; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Oligonucleotide Array Sequence Analysis; oral mucosa; Otorhinolaryngology. Stomatology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; squamous cell carcinoma; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Cytokeratin; Skin disease; Squamous cell carcinoma; Dysplasia; Basal cell carcinoma; Oral cancer; Stomatology; oral mucosa; Mucosa; Oral administration; Malignant tumor; Oral squamous cell carcinoma; Keratin; Anatomic pathology; Regulation(control); keratin 13; keratin 4; Oral cavity disease; epithelial dysplasia; Cancer
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2011.03759.x

Sakamoto K, Aragaki T, Morita K‐i, Kawachi H, Kayamori K, Nakanishi S, Omura K, Miki Y, Okada N, Katsube K‐i, Takizawa T & Yamaguchi A
(2011) Histopathology58, 531–542
Down‐regulation of keratin 4 and keratin 13 expression in oral squamous cell carcinoma and epithelial dysplasia: a clue for histopathogenesis
Aims:  This study aimed to identify relevant keratin subtypes that may associate with the pathogenesis of oral epithelial neoplasms.
Methods and results:  Expression of all the keratin subtypes was examined by cDNA microarray analysis of 43 oral squamous cell carcinoma (OSCC) cases. Immunohistochemical expression of the major keratins was examined in 100 OSCC and oral epithelial dysplasia (OED) cases. Many changes in keratin expression were observed and, significantly, consistent down‐regulation of keratin 4 (K4) and K13 expression was observed. Aberrant expression of K4 and K13 was associated with morphological changes in the affected oral epithelium. Experiments with cell cultures transfected with various keratin subtypes suggested that alterations in keratin subtype expression can cause changes in cell shape and movement.
Conclusions:  Aberrant expression of K4 and K13, which are the dominant pair of differentiation‐related keratins in oral keratinocytes, indicates dysregulation of epithelial differentiation in OSCC and OED. These keratins, especially K4, may be useful for pathological diagnosis. We propose that the aberrant expression of K4 and K13 and concomitant up‐regulation of the other keratins may be one of the causative factors for morphological alterations in the affected epithelium.