Phenotypic characterization of oral mucosa: what is normal?

Valach, Jaroslav; Foltán, René; Vlk, Marek; Szabó, Pavol; Smetana, Karel

doi:10.1111/jop.12556

Cited by 11 publications

(10 citation statements)

References 26 publications

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“…Previous reports have suggested that the downregulated expression of CK4 and CK13 in OSCC may cause morphological alterations in oral carcinogenesis and are relevant biomarkers of OSCC (8,21). The expression patterns of CK13, 4, 14, and 17 during the development of OSCC from oral precancerous lesions have also been investigated (22)(23)(24). The results of the present study were consistent with reports.…”

Section: Discussionsupporting

confidence: 92%

Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach

et al. 2018

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The current standard for the diagnosis of oral squamous cell carcinoma (OSCC) is based on the histologic examination of hematoxylin and eosin-stained sections; however, the discrimination among normal tissue, pre‑cancerous lesions and cancerous lesions can be difficult. The aim of the present study was to identify proteins with diagnostic significance in differentiating or predicting oral mucosal carcinogenesis. Proteomic profiling based on the laser capture microdissection of formalin-fixed, paraffin-embedded samples was performed, followed by liquid chromatography-tandem mass spectrometry (LC/MS) analysis. Immunohistochemistry (IHC) was used to evaluate the results. IHC of cytokeratins (CKs) was performed in neck dissection treatment cases. The accuracy rate and 95% confidence intervals (CIs) were used to evaluate the value of CKs as biomarkers of OSCC. A lymph node metastasis mouse model was used to validate the selected biomarkers. Among the proteins identified using LC/MS, several CKs exhibited significant differential expression patterns between the cancerous and para-cancerous tissues. The IHC results showed that negative staining of CK4 and CK10/13 distinguished cancerous from para-cancerous tissues with an accuracy of 90% (95% CI, 0.68-0.99) and 75% (95% CI, 0.51-0.91), respectively. Furthermore, the positive staining of CK14 and CK17 clearly distinguished cancerous from para-cancerous lesions with an accuracy of 100% (95% CI, 83-100%) and 90% (95% CI, 0.68-0.99), respectively. There was also CK14-positive staining in micro-metastases of lymph nodes in the clinical samples and in an animal model.

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Section: Discussionsupporting

confidence: 92%

Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach

et al. 2018

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“…Therefore, it has been used as a surrogate marker to rate the proliferation index particularly in the diagnosis for carcinogenesis [35]. Interestingly, there are indications regarding slightly different phenotype of oral and lip epithelium where Ki67 also may play a significant role [36]. The common functional significance of Ki67 still remains unclear both in healthy and in cleft affected tissue condition.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Cytokines and Proliferation Marker Ki67 in Cleft Affected Lip Tissue

et al. 2019

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Backgroundandobjectives: Cleft lip palate takes the second place among all anomalies. The complex appearance of cytokines and proliferation markers has still not been clarified despite their possible crucial role in cleft tissue. Therefore, the aim of work was the detection of appearance of pro- and anti-inflammatory cytokines and proliferation marker Ki67, and their inter-correlations in cleft affected lip (CAL). Materials and Methods: The lip material was obtained from 16 children aged before primary dentition during plastic surgery. Control was obtained from 7 non-CAL oral tissue. Tissues were stained for IL-1, IL-4, IL-6, IL-8, IL-10 and Ki67 immunohistochemically. Non-parametric statistic, Mann–Whitney and Spearman’s coefficient were used. Results: All cytokines positive cells were observed more into the epithelium. Statistically significant difference was seen between epithelial IL-1, IL-10, IL-8 and Ki67 positive cells and IL-10-, IL-4-containing connective tissue cells in comparison to the control. Strong positive correlation was detected in CAL epithelium between IL-10 and IL-8, IL-10 and IL-4, IL-10 and IL-1, IL-1 and IL-8, IL-1 and IL-4, IL-4 and IL-8, IL-8 and Ki67, IL-10 and Ki67, but moderate—in connective tissue between IL-1 and IL-10, IL-1 and IL-4. Conclusions: The CAL epithelium is the main source for the interleukins. Rich similar expression of IL-1 and IL-10 suggests the balance between pro-and anti-inflammatory tissue response on basis of dysregulated tissue homeostasis (increase of IL-8). The correlations between the different ILs-1, -4, -8, -10 in CAL epithelium seem to indicate the self-protection compensatory mechanism for intensification of local inflammatory-immune response without involvement of IL-6. The correlations between Ki67 and cytokines indicate the involvement of IL-8 and IL-10 in stimulation of cellular proliferation. IL-4 and IL-10 expression from CAL connective tissue simultaneously to IL-1, IL-4 and IL-10 inter-correlations there suggests the intensification of local immune response regulated probably by main pro-inflammatory cytokine—IL-1.

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“…Previous investigations have shown that epithelial expression of keratins is altered in OLP compared with normal oral mucosa and this can therefore affect the functions mentioned above: keratin 1 (K1)/keratin 10 (K10) , K14 , keratin 6 (K6)/keratin 16 (K16), and K19 are reported to be upregulated in OLP, whereas keratin 4 (K4) , K4/keratin 13 (K13) , keratin 5 (K5)/keratin 15 (K15) , and K19 are reported to be downregulated. Data on K8 and K18 expression in oral keratinocytes of normal oral mucosa are inconsistent, varying from reports of absence to sporadic presence . While K19 has been found to be downregulated in OLP , the pairwise expression of K8 and K18 in OLP has not been systematically studied.…”

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confidence: 98%

Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus

Schreurs

Karatsaidis

Balta

et al. 2020

European J Oral Sciences

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Keratins form intermediate filaments of the cytoskeleton in keratinocytes and have roles in cell structure, signaling, intracellular transport, and cell death. Oral lichen planus (OLP) is an oral inflammatory disease with derangements in basal keratinocytes and disruption of the basal membrane. Here, we focused on epithelial expression of keratins 8, 18, and 19 because these proteins are known to modulate cell death. Biopsies were taken from buccal oral mucosa of persons with normal oral mucosa (n = 10) or atrophic OLP (n = 10). Cultured normal oral keratinocytes (n = 4) showed expression of mRNA and protein for keratins 8, 18, and 19. Immunohistochemistry showed consistent staining for keratins 8 and 18 in basal keratinocytes of normal oral mucosa. In OLP, staining for keratin (K)8 was mostly negative and staining for K18 was weak. Keratin 19 was expressed irregularly in most biopsies of normal oral mucosa and not at all in OLP. Several mononuclear leukocytes in the cellular infiltrate showed membrane staining for K8 and K18. Positive staining for K16 confirmed partial collapse of the basal cell layer in OLP. The basal cell niche in OLP therefore appeared to be partly populated with keratinocytes demonstrating a higher degree of differentiation (K8− K18− K19− K16+); consequently, such areas may be more susceptible to the action of cell death factors released from the cell infiltrate as a result of lacking the protective, normal keratin present in the basal epithelial cell layer of normal oral mucosa.

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Phenotypic characterization of oral mucosa: what is normal?

Abstract: These results demonstrated oral epithelium phenotypic plasticity based on functional requirements of the microenvironment, which can be used in diagnosis.

Cited by 11 publications

References 26 publications

Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach

Screening diagnostic biomarkers of OSCC via an LCM-based proteomic approach

Characterization of Cytokines and Proliferation Marker Ki67 in Cleft Affected Lip Tissue

Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus

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