In situ hybridization study of cytokeratin 4, 13, 16 and 19 mRNAs in human developing junctional epithelium

Cytokeratins (CKs) are now considered to be reliable markers for following the development and differentiation of epithelial tissue. We have investigated the pathway of differentiation in human developing junctional epithelium using monoclonal antibodies and two-dimensional gel electrophoresis of mcrodissected tissue to identify CK 19. CK 16. CK 14. CK 13. CK 6. CK 5. CK 4 in the junctional epithelium (JE) over partially erupted human teeth. The CK profile was similar to that of developing oral epithelia. suggesting that the junctional epithelium in teeth during eruption is of odontogenic origin. The present study used in situ hybridization to determine the distribution of the mRNAs of CKs 19. 16. 13 and 4 in human developing junctional epithelium and to examine the correlation between mRNAs and their encoded proteins. CK 19 mRNA was abundant in the basal cell layers of the primary junctional epithelium (PJE) but less concentrated in the suprabasal layers. CK16. 13 and 4 mRNAs were abundant in the basal cell layers of the PJE. Tlie parabasal cell layers reacted intensely to the cRNA probe complementary to CK16 mRNA. as were the reactions in the suprabasal cell layers of the PJE for the CK 13 and 4 probes. Our results demonstrate that the PJE express the genes encoding for CKs 16 and 4 that have been revealed previously only by electrophoresis. They therefore confirm that the PJE is a well-differentiated stratified epithelium with a complex unique phenotype that produces CKs specific for basal cells (CK 19), CKs associated with hyperproliferation (CK 16). and finally those associated with stratification (CKs 4 and 13). Only synthesis of CK 19 protein and mRNA are strictly parallel. CKs 4 and 13 mRNAs are present in basal and suprasal cells, while their encoded proteins were not. except for CK 13 in suprabasal cell layers of PJE. where the amount of its mRNAs was coincident with the expression of the protein.     

单层上皮细胞角蛋白在口腔粘膜癌变过程中的表达

目的：探讨单层上皮细胞角蛋白ＣＫ１８和ＣＫ１９作为口腔癌前病变标志的可能性。方法：用ＬＳＡＢ免疫组化染色方法检测ＣＫ１８和ＣＫ１９在福尔马林固定,石蜡包埋的口腔正常粘膜,上皮单纯增生,轻度上皮导演增生,中度上皮异常增生,重度上皮异常增生和口腔鳞癌组织中的分布和表达强度,光镜观察染色切片,结果用秩和检验分析。     

人牙龈结合上皮、口腔龈上皮及沟内上皮中细胞角蛋白的表达

目的 检测人牙龈上皮的细胞角蛋白(CK)谱，探讨结合上皮(JE)与口腔龈上皮(OE)、沟内上皮(SE)的不同。方法 5例人磨牙及前磨牙牙龈颊舌向石蜡切片，采用免疫组化SP法行CK5／6、7、8／18、10／13、16、17、19、20染色。结果 CK7、17在3种上皮中均无表达；CK5／6、20在3种上皮的基底上层(尤其是近表层)为弱阳性及阳性表达，基底层无表达；CK10／13、16在JE全层均有表达，在OE和SE仅限于基底上层，其中CK10／13为强阳性，CKl6为弱阳性及阳性；CK19在JE全层强阳性，在OE和SE仅限于基底层，JE和SE分界明显；CK8／18与CK19相似，只是表达较弱，近基底层的基底上层也有少量表达。结论JE是一种不同于OE和SE的特殊低分化上皮，CK19可作为JE的特征性标记物区别于OE和SE，CK10／13、16可用于体外培养的上述3种细胞的鉴别。     

Cytokeratin profile of the junctional epithelium in partially erupted teeth

This study uses cytokeratins (CK) as markers to investigate the phenotype of the junctional epithelium (JE) in partially erupted human teeth. The gingival samples, which were clinically healthy, were carefully dissected from the teeth. Cryostat sections were cut for histological staining, immunofluorescence microscopy and gel electrophoresis. Cytokeratins were extracted after microdis-section. The basal and suprabasal epithelial cell markers, cytokeratins 4, 5, 13, 14 and 19 were detected with specific monoclonal antibodies. They showed that the junctional epithelium in erupting teeth has a complex topography. The cytokeratin immunohistochemical profile distinguished between the primary junctional epithelium (CK 5, 14 and 19 in basal and suprabasal cells and CK 13 faintly stained throughout the suprabasal layers) and the adjacent epithelium that had the same cytokeratin profile as the sulcular epithelium (CK 5, 14 and 19 in basal cells and CK 4 and 13 intensively stained in the suprabasal cells). Extraction, two-dimensional electrophoresis and western blotting showed that this transitional JE during eruption also contained CK 6, 16 and perhaps CK 4. Thus, the JE in erupting teeth shows patterns of CK distribution that are very similar to that of developing oral epithelia.     

Immunohistochemical study during healing of free palatal mucosa grafts on plastic-embedded samples

This immunohistochemical study describes changes in the histology and in the distribution of the basement membrane components laminin and collagen IV as well as of the cytokeratins (CK)1/2/10/11, CK5/6, CK13, CK14, CK17, CK19 during the take of free split mucosa (epithelial and connective tissue) transplants in humans up to 36 months post-operative. Histology showed a flattening of the epithelial layer within the first 2 weeks after grafting, followed initially by an increase (25-30 layers, week 6) and later on by a decrease of cell layers in the epithelium (15-20 layers, week 20). From that time onwards, clear stratification and reteridges as signs of differentiation were present. Up to day 14 of graft take, the linear staining patterns for laminin and collagen IV were interrupted, which was not observed at any later stage. During this early interval CK5/6, CK1/2/10/11, CK14 and CK17 were expressed in all epithelial layers. The reactions for CK5/6 and CK1/2/10/11 were less intensive. At 6 weeks, CK1/2/10/11 stained the intermediate and superficial layers, being consistent with findings after longer graft take. CK5/6 reacted in the basal and intermediate cell layers, and CK13, CK14 and CK17 reacted in all layers. In the following period up to week 20, CK5/6 were found in the parabasal cells of the intermediate cell layers and the basal cells. CK14 staining was confined to these cell layers too, but also showed some reaction in the superficial layers. CK13 and CK17 were still bound to all layers. At 7 months post-operative, CK5/6 and CK14 were seen in their typical localisation in the basal cell layer and the parabasal cells of the intermediate layers, CK17 was seen mainly in the intermediate layer and CK13 was seen in focal areas of all layers. Anti-CK19 reacted only with single basal and parabasal cells up to week 20. These results suggest that during healing of mucosal autografts there is a sequence of changes in the expression of cell biological differentiation markers that may involve an epithelio-connective tissue interaction before the typical patterns for the donor side were observed again on the gingiva or mucosa of the hard palate.     

Construction and characterization of human oral mucosa equivalent using hyper-dry amniotic membrane as a matrix

BackgroundHuman amniotic membrane(HAM) as a graft material has been used in various fields. Hyper-dry amniotic membrane (HD-AM) is a novel dried amniotic membrane that is easy to handle and can be preserved at room temperature without time limitation. The purpose of this study was to investigate the useful properties of HD-AM in reconstruction of the oral mucosa.MethodsHuman oral keratinocytes were isolated and seeded on HD-AM in serum-free culture system. Oral mucosa equivalent (OME) was developed and transplanted onto full-thickness wound on athymic mice. The wound healing was analyzed and the OME both before and after transplantation was analyzed with hematoxylin-eosin staining and immunohistochemicial staining for Cytokines 10 (CK10), Cytokines 16 (CK16), and Ivolucrin (IVL).ResultsOral keratinocytes spread and proliferated well on HD-AM. Two weeks after air-lifting, OME had formed with good differentiation and morphology. We confirmed immunohistochemically that the expression of CK10 was positive in all suprabasal layers, as was CK16 in the upper layers, while IVL was present in all cell layers. Three weeks after transplantation to athymic mice, the newly generated tissue had survived well with the smallest contraction. The epithelial cells of newly generated tissue expressed CK10 throughout in all suprabasal layers, IVL was mainly in the granular layer, and CK16 positive cells were observed in all spinous layer and granular layer but were not expressed in the mouse skin, all of which were similar to native gingival mucosa.ConclusionsThe OME with HD-AM as a matrix revealed a good morphology and stable wound healing. This study demonstrates that HD-AM is a useful and feasible biomaterial for oral mucosa reconstruction.     

Cytokeratin patterns of human oral mucosae in histiotypic culture.

In a three-dimensional culture model, oral epithelial differentiation was investigated ultrastructurally and biochemically for cytokeratin expression. Epithelia from the hard palate, gingiva and alveolar mucosa grown on freely floating collagen lattices populated with fibroblasts from homotypic origins, and fed with medium containing 10% delipidized fetal calf serum for 21 days before analysis, stratified and differentiated to basal cuboidal cells, polyhydral spinous cells and elongated superficial cells. The epithelium of palatal origin had non-nucleated superficial cells resembling orthokeratinized cells. The upper spinous cells had keratohyalin-like granules. The corresponding cells of gingival and alveolar mucosal origins retained their nuclei and had smaller numbers of keratohyalin-like granules. Basal cell keratins (CK 5 and 14) and those of hyperproliferation (CK 6 and 16) were consistently found in all epithelia. Furthermore, simple epithelial keratins (CK 18 and 19) were variably expressed by cells from different oral origins. In epithelial cells from the alveolar mucosa, CK 13 and 19 formed major bands, which correlates with their expression in vivo. In contrast, these polypeptides were either absent or formed minor bands in extracts of gingival and hard palatal cells. Although in small quantities, keratins of terminal differentiation (CK 1, 2, 10 and 11) were detected in gels prepared from palatal epithelia. This expression correlates with the higher morphological differentiation of these cells in this model. The model is of interest for studies of epithelial differentiation, as the differentiation markers of keratinized epithelia (CK 1 and 10) were expressed by cells from palatal origin, and those of non-keratinized epithelia (CK 4, 13 and 19) were prominent in cells from alveolar mucosal origin.     

Effect of snuff on cytokeratin expression in oral vestibular sulcus epithelium

Differences in the expression of cytokeratins (CK) in specimens obtained from snuff-affected oral epithelium of the maxillary vestibular sulcus and clinically normal sulcular epithelium were studied by indirect immunofluorescence staining with a panel of monoclonal antibodies (MAbs), CK 14, a marker of stratified squamous epithelium, was not seen expressed in 3/11 of the snuff user's specimens. Terminal differentiation markers, typical of ramified epithelia (CK 1, 9, 10 and 11). were detected suprabasally in the snuff user's keratosis but not in the normal control epithelium. The use of snuff seemed to change the CK staining pattern of the mucosa so that it resembles more that of a cornfield type of epithelium. Simple epithelial-type CK were included in the study in order to establish the CK profile of the snuff-induced keratosis, for comparison with normal and dysplastic lesions. MAb to CK 7 and 19 showed reactivity in the basal cells and suprabasally, whereas the monospecific MAb anti-CK 7 showed suprabasal staining both in the control and affected epithelia. By using MAbs, we found no immunoreactivity against CK 18 either in normal or affected epithelia, whereas we found suprabasal reaction (5/11) against CK 8 in the snuff user's epithelia. The two MAbs demonstrating the expression of CK 19, normally confined to the basal cells of the stratified squamous epithelium, showed variable patterns of expression both in basal cells and suprabasally in the snuff lesions. The results show that use of oral snuff causes some alterations in the CK expression pattern of the affected epithelium. Whether the alterations are indicative of a premalignant change is, however, uncertain. The results encourage further studies on the subject.     

Oral lichen planus: an immunohistochemical study of heat shock proteins (HSPs) and cytokeratins (CKs) and a unifying hypothesis of pathogenesis

The expression of heat shock proteins HSP60 and HSP70 and cytokeratins CK1/10 and CK7/18 were compared in epithelium of oral lichen planus (OLP) lesions and oral fibromas using an avidin-biotin-peroxidase complex (ABC) immunohistochemical method. An immunostaining intensity distribution (IID) index was developed to assess staining intensity and the proportion of positively stained cells in different layers of the epithelium. The expression of HSP60 in the basal layer was significantly higher in OLP than in fibromas. No difference in HSP70 expression was evident between OLP and fibromas. The expression of CK1/10 in the epithelial basal and suprabasal layers was significantly higher in OLP than in fibromas. There was no demonstrable staining for CK7/18 in either OLP or fibromas. A significant correlation was evident between the expression of HSP60 and CK1/10 in the basal epithelial cells in OLP. The findings support a role for HSP60 in the pathogenesis of OLP. A unifying hypothesis of the pathogenesis of OLP, involving two sequential immune reactions, is proposed.     

Cytokeratins as epithelial differentiation markers in premalignant and malignant oral lesions

The keratin expression pattern in oral stratified epithelium is related to the cellular differentiation level. The normal pattern shows the keratin pair K5 and K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs associated with differentiating suprabasal cells. Monoclonal and polyclonal antibodies to individual keratins (K10, K13 and K14) were used in a two-color immunofluorescence staining method to study their coexpression in single cells. Altered keratin expression in premalignant and malignant lesions indicated abnormal differentiation. Monospecific keratin antibodies were suggested to be useful for evaluation of epithelial differentiation changes in oral dysplasias and oral squamous cell carcinomas.     

口腔粘膜疣状癌基膜的免疫组化和超微结构研究

目的 研究口腔粘膜疣状癌基膜Ⅳ型胶原与层粘连蛋白的表达、分布和超微结构改变。方法 采用免疫组化S－P法,分别检测16例疣状癌、10例鳞癌和9例中至重度不典型增生病例中Ⅳ型胶原与层粘连蛋白的表达,对表达结果作定量分析,并对3例疣状癌作电镜观察。结果 疣状癌基膜大多数较厚且保持完整（13／16）,电镜下观察基板在一些区域明显增厚。但炎症细胞较多的病例,基膜出现中断（3／16）。鳞癌和中至重度不典型增生基膜相对较薄,鳞癌基膜绝大多数不连续（9／10）,尤其在浸润的前沿或小条索状癌结构中,基膜基本中断或消失。中至重度不典型增生基膜大多数连续（6／9）。所有病例的癌巢周围间质中都可见炎症细胞浸润,疣状癌较鳞癌和中至重度不典型增生中浸润的淋巴细胞更为密集（P＜0．05）。在疣状癌中,上皮内炎症细胞浸润与其基膜完整呈正相关关系（P＜0．01）。结论 疣 状癌基膜较厚,较完整且结缔组织中有大量以淋巴细胞为主的炎症细胞浸润,可能与生物学行为有关。     

大鼠舌癌变细胞分化异常的表型特征——角蛋白谱分析

目的　阐明口腔癌变细胞分化异常的表型特征。方法　 L SAB免疫组化方法检测 69例 4-硝基喹啉 -1-氧化物 ( 4 NQO)口服诱发大鼠舌癌变各期组织分化标志角蛋白 ( CK) 10 ,13 ,14的表达。结果　随口腔癌变进展 ,CK14自基底层向上逐渐延伸至基底上层表达 ;基底上层 CK13表达逐渐减少 ;基底上层 CK10表达在癌前逐渐上升 ,成癌后则聚然下降。结论　口腔癌变是一种细胞分化异常疾病 ,该过程中角蛋白谱的变化是上皮细胞分化异常的主要表现     

Immunohistochemical study of the orthokeratinized odontogenic cyst: a comparison with the odontogenic keratocyst

OBJECTIVE: Orthokeratinized odontogenic cyst (OOC) is a developmental cyst that occurs in the maxilla and the mandible and is defined by the World Health Organization as the uncommon orthokeratinized type of odontogenic keratocyst (OKC). However, studies have shown that OOC has peculiar clinicopathologic aspects and biologic behavior when compared with other developmental odontogenic cysts, especially OKCs. Therefore, in this study, the immunohistochemical profile of the OOC was delineated and compared with that of the OKC. STUDY DESIGN: Twelve cases of OOC were submitted to a panel of antibodies composed of cytokeratins (10, 13, and 14) and extracellular matrix proteins: fibronectin, types I and III collagen, and tenascin. For comparative means, 12 cases of OKC also were submitted to the same panel of antibodies. RESULTS: The results obtained showed that OOCs expressed cytokeratin 10 and showed variable expression of cytokeratins 13 and 14. Fibronectin and collagen types I and III also were expressed in OOC in a fibrillar aspect. OKC showed only the superficial keratin layer positive to cytokeratin 10 and the basal and suprabasal layers with variable expression of cytokeratin 14, and cytokeratin 13 was present in the upper epithelial layers. The extracellular matrix proteins showed a nonfibrillar expression. Tenascin was immunoexpressed only in OKC. CONCLUSION: The immunohistochemical profile of the studied cysts clearly showed that OOC presents a well-formed cystic enveloping, whereas the OKC profile is compatible with a more aggressive biologic behavior.     

Proliferation and differentation markers in snuff-induced oral mucosal lesions

BACKGROUND: Regular use of snuff is known to cause whitish oral mucosal lesions of variable severity at the usual quid placement site. The main aim of this study was to elucidate cellular mechanisms involved in snuff-induced epithelial changes. METHODS: Expression patterns for markers of cell proliferation (PCNA, Ki-67), cell cycle regulation (p53, p21), keratin changes (pankeratin, CK18, CK19), cell stress (HSP 70) and collagen type IV in 14 snuff-induced oral mucosal lesions and 12 control samples were analyzed by immunohistochemistry (IHC). RESULTS: On light microscopy, all snuff-induced lesions were characterized by a hyperkeratinized and thickened epithelium. Some vacuolized cells, markers of cell degeneration, were frequently seen (in 9/14 of the samples) in the superficial layers in epithelia. Expression of PCNA and Ki-67 was found in a statistically significantly fewer cells in snuff-induced lesions (P < 0.001) than in the controls. This indicates that epithelia in snuff-induced lesions are not thickened as a result of increased cellular proliferation, but by protracted turnover of differentiating cells. Of cell cycle markers, p21 was found be up-regulated in 4/14 snuff-induced lesions, probably by p53-independent pathways. Only two snuff-induced lesions showed p53 positivity. However, the number of stained cells with p53 and p21 was not statistically different from that in controls. Expression of CK18, but not any alterations in CK19 expression, was seen in 5 of 14 snuff-induced lesions. Snuff also seems to stimulate the expression of collagen type IV, possibly by basal cells, as indicated by the thickened staining of the basal lamina. CONCLUSIONS: The findings of this study showing suppressed cellular proliferation and infrequent p53 dysfunction in snuff lesions may partly explain why dysplastic changes are seldom seen in mucosal lesions induced by the Scandinavian type of snuff.     

Vestibuloplasty: Porcine Collagen Matrix Versus Free Gingival Graft: A Clinical and Histologic Study

Background: A free gingival graft (FGG) is currently the gold standard for augmenting small areas of keratinized mucosa. The porcine collagen matrix (CM) represents an alternative to autologous tissue harvesting. This study aims to compare the CM versus FGGs for augmenting keratinized peri‐implant mucosa based on clinical and histologic evaluations. Methods: The study included 14 patients who underwent a vestibuloplasty with either a FGG from the palate (n = 7) or the CM (n = 7). An implant‐fixed vestibular retention splint was inserted for 30 days. Follow‐up examinations were performed at 4, 10, 30, and 90 days after surgery. Width of keratinized mucosa was measured in the region of each implant (days 10, 30, and 90). After 90 days, a biopsy was harvested for histologic and immunohistologic analyses. To characterize newly formed soft tissue, the authors stained for tissue‐and differentiation‐specific markers, cytokeratin (CK) 5/6, 13, and 14, to detect presence or absence of keratinization. Results: The groups showed similar healing, with increased peri‐implant keratinized mucosa. The CM group had overall significantly shorter operation times than the FGG group. Both groups showed similar overall shrinkage (32.98% CM versus 28.35% FGG). All biopsies showed a multilayered, keratinized, squamous epithelium. CKs 5/6 and 14 were detected in the basal and suprabasal layers, and spots of CK 13 were detected in the suprabasal layer. Conclusions: During the whole observation period, both groups showed comparable clinical and histologic outcomes. Within the limitations of the present study, CM seems to be a promising alternative for the regeneration of keratinized mucosa without tissue harvesting. Comparative long‐term studies are needed to investigate changes over time.     

口腔畸胎样囊肿临床病理与免疫组化研究

目的 分析31例口腔畸眙样囊肿的临床病理及免疫组化特点。方法 复习武汉大学口腔医学院1963至2003年病理档案资料及切片，31例符合Meyer的口腔畸胎样囊肿诊断标准。全部病例行组织学、组织化学和角蛋白免疫组织化学研究。结果 本组病例约占同期颌面部软组织囊肿的1．85％。31例中，儿童为27例，其中24例为先天性，男女比为1：0．55；口底和舌部分别为22例和8例；突出的临床特征为膨胀性生长；手术完整摘除，预后好。组织学观察该囊肿除复层鳞状上皮衬里外，还有呼吸道上皮和(或)胃肠上皮，其中8例含单层立方上皮。角蛋白免疫组化结果显示，AE1／AE3在4种上皮中均为阳性表达。AE1、CK8／18和CK7分别在少数复层鳞状上皮基底层和表层表达，所有复层鳞状上皮基底层表达CK19，而AE1、CK7、8／18和CK19在其余3种上皮中均呈阳性表达。CK16在4种上皮中均呈弱阳性表达，CK20仅在胃肠上皮呈阳性表达。结论 口腔畸眙样囊肿主要发生于儿童，口底和舌部为好发部位，镜下组织结构多样，角蛋白标记结果显示囊肿不同的上皮成分与机体相应部位的上皮表型相似，提示了衬里上皮的不同起源与分化。     

Changes in oral cytokeratin expression in HIV-infected subjects with long-term use of HAART

Oral Diseases (2012) 18 , 793–801 Objectives: The objectives of this study were to determine (i) the expression of oral cytokeratins (CKs) among human immunodeficiency virus (HIV)‐infected subjects compared with non‐HIV controls, (ii) the oral CK expression in the subjects with highly active antiretroviral therapy (HAART) compared with those without HAART, and (iii) factors associated with the expression of oral CKs. Materials and methods: Oral tissues from buccal mucosa were obtained by punched biopsy in HIV‐infected subjects with and without HAART, and non‐HIV individuals. The samples were processed for immunohistochemical studies of CK1, CK13, CK14, CK16, and involucrin. The staining intensity was scored and recorded. Logistic regression analysis and multi‐way ANOVA test were performed. Results: The expression of CK13, CK14, and CK16 was found to be significantly different between HIV‐infected subjects and non‐HIV individuals (P < 0.05). The expression of those CKs was also significantly different between those who were and were not on HAART (P < 0.05). No significant difference between the groups was observed regarding CK1 and involucrin. Conclusions: Oral epithelial cell differentiation as marked by the CK expression is affected by HIV infection and use of HAART. CKs may be the useful biomarkers to identify HIV‐infected subjects who are at risk of malignant transformation of the oral mucosa because of HIV infection and HAART.     

An altered keratinocyte phenotype in oral submucous fibrosis: correlation of keratin K17 expression with disease severity

Oral submucous fibrosis (OSF) is characterized by abnormal collagen metabolism in the submucosal connective tissue. Its influence on the overlying epithelium is not known but about 14% of OSF cases undergo malignant transformation to squamous cell carcinoma indicating association with abnormality of the epithelium. Here, we have defined the keratin expression profile, by immunohistochemistry and quantitative image analysis, using a panel of 22 anti-keratin monoclonal antibodies on 28 OSF samples. We observed an increase of K1 and K10 in the suprabasal layers, induction of K6 in the basal layer and complete loss of K19 in the epithelium. Furthermore, there was increased K17 expression in the suprabasal layers, which correlated with disease severity. In a subset of the most severe OSF cases (14%), K17 expression was completely lost in the basal layer which might define them to be at most risk to undergo malignant transformation. There was no detectable expression of K8, K18, K7 and K9 and the expression of K4, K13, K14, K15 and K16 did not change in OSF. We propose that the altered keratin profiles could be useful as histological diagnostic markers and provide important insights into the pathogenesis of the disease and its predisposition to malignancy.     

口腔粘膜癌变过程中细胞角蛋白CK10和CK13的变化

目的：探讨细胞角蛋白ＣＫ１０和ＣＫ１３在口腔粘膜癌变过程的各阶段组织中的分布和表达强度。方法：用ＬＳＡＢ免疫组化染色方法对口腔正常粘膜、上皮单纯增生、上皮异常增生和口腔磷癌切片进行染色,光镜观察。结果：正常颊粘膜和口底舌腹粘膜基底上层ＣＫ１０表达阴性,ＣＫ１３表达强阳性;上皮过度不全角化时,ＣＫ１０表达可为阳性,ＣＫ１３表达减少;上皮过度正角化时,ＣＫ１０在基底上层呈强阳性表达,ＣＫ１３表达进一步减少甚至缺失。随上皮异常增生程度加重,基底上层细胞ＣＫ１０和ＣＫ１３表达减少甚至缺失。在口腔浸润癌中,不管分化程度如何,ＣＫ１３均表达阴性,而ＣＫ１０在分化较好的癌细胞及癌巢中呈阳性表达。结论：ＣＫ１３表达减少或缺失可作为口腔癌前病变诊断的辅助指标,ＣＫ１０可为口腔癌的分化程度及其预后判定提供帮助。