Emergence of keratin 17 vs. loss of keratin 13: Their reciprocal immunohistochemical profiles in oral carcinoma in situ (original) (raw)
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The American journal of pathology, 1994
Simple epithelial keratins K7, K8, and K18 are present in no more than trace amounts in normal stratified squamous epithelial but have been reported in squamous cell carcinomas. With the aim of determining the level at which keratin synthesis is regulated in vivo, we have compared the expression of mRNA by in situ hybridization and protein by immunohistochemistry for K7, K8, and K18 in a series of normal, dysplastic, and malignant oral epithelia. In normal epithelia mRNAs for K7, K8, and K18 were present in basal and lower spinous cells but adjacent sections were generally negative for the respective proteins. In severe dysplasia there was irregular suprabasal extension of K8 and K18 mRNAs in all cases and their proteins were expressed in more than half of the cases. The carcinomas expressed K8 and K18 mRNAs homogeneously and were strongly reactive for these keratin proteins but K7 expression appeared reduced in malignancy. These results are consistent with the post-transcriptional ...
Head and Neck Pathology, 2010
K19 is an intermediate filament protein that has been investigated in oral squamous cell carcinoma (OSCC), but that has not been correlated with the amount of keratin produced within well-differentiated OSCC grade. The aim of the present study was to objectively analyze K19 immunoexpression in OSCC and to validate the utility of K19 in differentiation among grades of oral epithelial dysplasia (OED). Formalin-fixed tissues of 36 primary OSCC (22 well, 10 moderately, 4 poorly differentiated), 43 OED (23 mild, 8 moderate, 12 severe), and 11 normal oral epithelium (NOE) were included. K19 was immunostained using HRP-DAB method. The percentage of K19-positive area was found using color deconvolution program in ImageJ Ò image analysis system (public domain software,
Histopathology, 2011
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 downregulation 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.
Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma
Genetics and Molecular Research, 2015
Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the B.A. Coelho et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 15123-15132 (2015) expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.
Pattern of keratinization in oral squamous cells during carcinogenesis
Background: Oral carcinogenesis is a multi-step process. Broadly, oral squamous cell carcinoma (OSCC) can be well-, moderately- or poorly-differentiated, and either keratinizing or non-keratinizing. Most cases are moderately to poorly-differentiated. Precursor lesions (dysplasia) can be categorized into mild, moderate, or severe (carcinoma in situ).In the present study, the pattern of keratin expression in oral squamous cells during carcinogenesis is vividly analysed. Materials and Methods: Samples in the form of scraped and exfoliated cytosmear were collected from the affected sites of the clinically diagnosed 136 oral cancer patients and were immediately fixed in acetoalcohol (1:3). The wet fixed smears were stained by routine Papanicolaou’s staining protocol and Giemsa’s solution. Stained tissues were studied under the microscope. Results: Cytological pleomorphism is a unique feature observed during carcinogenesis. There appears to be a spectrum of degrees of keratinization rather than distinct types, and the degree of keratinization is reflected in the degree of packing and orientation of keratin filaments. It is presumed that alteration in the architectural regularity of the cell membrane is an important aspect of keratinization which leads to cytological pleomorphism during oral carcinogenesis. Conclusion: Pattern of keratinization alongwith cytological pleomorphism in exfoliated epithelial squamous cells has a practical utility in the diagnosis and early detection of oral cancer during carcinogenesis. Keywords: Carcinogenesis, Keratinization, Keratins, Oral squamous cell carcinoma.
Epithelial expression of keratinocytes growth factor in oral precancer lesions
Dental Research Journal, 2016
Background: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. Materials and Methods: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. Results: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. Conclusion: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated.
Contemporary Clinical Dentistry, 2013
Background: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). Aim: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. Materials and Methods: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI). Results: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant (P < 0.001). The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. Conclusion: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.
Keratins are cytoplasmic intermediate filament proteins preferentially expressed in epithelial tissues (Moll et al., 2008; Moll et al., 1982). They are subdivided into the type I acidic (K9-K28) and type II basic (K1-K8 and K71-K74) keratins (Schweizer et al., 2006). They are obligatory heteropolymers and are coexpressed in various epithelia in specific pairs consisting of one type I and one type II keratin (Coulombe and Omary, 2002; Fuchs and Weber, 1994). Epithelial tissues express different pairs of keratins depending upon the epithelial cell type and stage of differentiation (e.g. all stratified squamous epithelia express K5 and K14, whereas K8 and K18 are seen in all simple epithelia) (Coulombe and Omary, 2002). Keratin filaments are connected with cell adhesion complexes, such as hemidesmosomes and desmosomes, at the cell membrane (Green and Jones, 1996) and provide mechanical support to tissue architecture (Fuchs and Cleveland, 1998). At hemidesmosomes, keratin networks are associated with 4 integrin through plectin and dystonin (also known as BP230) (Borradori and Sonnenberg, 1996; Yang et al., 1996). In addition to their scaffolding function, keratins form complex signalling platforms and interact with various kinases, adaptors, receptors and apoptotic proteins, thus regulating and/or modulating associated signalling pathways (Paramio and Jorcano, 2002). K8 and K18 are expressed in all simple epithelial cells and execute various regulatory functions (Coulombe and Omary, 2002; Owens and Lane, 2003), which include modulation of protein localization, targeting, trafficking and synthesis (Coulombe and Omary, 2002; Omary et al., 2009; Owens and Lane, 2003). K8 and K18 expression is not observed in stratified adult epithelial tissues; however, these proteins are often aberrantly expressed in squamous cell carcinoma (SCC), where their expression is correlated with invasion and poor prognosis (
Expression of Keratin 75 (K6hf) in Oral Squamous Cell Carcinoma
Dental Medicine Research, 2011
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the head and neck region, afflicting about 300,000 patients worldwide each year. 1, 2 For many years, the 5-year survival rate of OSCC patients has remained relatively low, only approximately 50-60% 3, 4 and the rate is even lower in patients diagnosed at later stages. Although early diagnosis and efficient treatment are the keys to the prognosis of OSCC, up to date, specifi c biomarkers for early diagnosis and prognostic monitoring of OSCC are lacking. Cytokeratin is over-expressed in tumor tissue compared to normal oral mucosa. 5 7 Furthermore Keratin 13 (K13) is decreased in OSCC. 8 Therefore, these cytokeratin alterations may be used as diagnostic marker of OSCC. The type II keratin 75 (keratin 6hf; K6hf) has been described as being specifically expressed in the companion layer of the hair follicle 9 in human skin. This distinct compartment consists of a single layer of fl attened cells located at the interface between the outer root sheath, a stratifi ed epithelium contiguous with the epidermis, and the inner root sheath, a three-layered compartment located between the companion layer and hair shaft. 9 11 However, correlation of OSCC and K6hf remains unclear. In recent years, proteomics has emerged as a powerful technology to identify differential protein expressions associated with cancer development and progression. In particular, laser microdissection and LC/MS/MS method using tissue sections accompanied by both definitive diagnoses and known clinical outcomes provide a great opportunity for biomarker discovery. 12 15 In this study, we use this method and try to discover biomarker of OSCC. As a result, K6hf is identified
Head & neck, 2018
Background: Overexpression of keratin 17 (K17) is highly associated with poor prognosis in squamous cell carcinoma (SCC) of the cervix. This study was performed to (1) determine whether K17 may be a prognostic biomarker in head and neck squamous cell carcinoma (HNSCC) and (2) to establish if K17 expression is associated with human papillomavirus (HPV) status. Methods: Immunohistochemical staining was performed for K17 of oral, oropharyngeal, and laryngeal SCCs, and normal oropharyngeal mucosa. The HPV status was determined using polymerase chain reaction (PCR). Results: Elevated K17 expression was significantly associated with an overall decreased patient survival (P 5 .02) and, more specifically, in patients with oropharyngeal SCC (P 5 .01). When controlling for HPV status and tumor location K17 was still a significant predictor of survival (P 5 .01). Conclusion: Therefore, K17 is a novel prognostic biomarker of poor survival for patients with HNSCCs, controlling for anatomic site and HPV status.