Nerve growth factor beta/pro-nerve growth factor and their receptors in normal human oral mucosa

Nerve growth factor beta (NGF-beta) and its precursor proNGF are important for the differentiation and survival of neurons and dermal keratinocytes. The aim of this study was to determine the role that NGF might play in the differentiation and wound healing of oral mucosa. Cultured normal human oral mucosal keratinocytes expressed mRNA for NGF-beta/proNGF and for their receptors TrkA and p75(NTR). Lysates from cultured oral mucosal keratinocytes did not contain detectable amounts of mature 14-kDa NGF-beta but did contain several NGF proforms with molecular weights between 32 and 114 kDa. Culture medium from oral mucosal keratinocytes contained 75 kDa proNGF. The addition of NGF-beta significantly enhanced the proliferation of oral mucosal keratinocyte cultures and in vitro scratch closure. Immunostaining of biopsies from normal oral mucosa showed the presence of proNGF in all epithelial layers. NGF staining was observed in the granular and upper spinous cell layers. TrkA immunoreactivity was detected in basal and parabasal cells, with weak to moderate staining in spinous and granular cell layers. p75(NTR) staining was seen in basal cell layers. These findings indicate that NGF-beta/proNGF have mitogenic and motogenic effects on oral mucosal keratinocytes and therefore may aid in the healing of oral wounds. Differential expression of NGF and NGF receptors throughout the epithelium suggests a role in epithelial differentiation.     

Altered CD40 and E-cadherin expression – putative role in oral lichen planus

BACKGROUND: Oral lichen planus (OLP) is characterized among other features by apoptosis of basal keratinocytes. To identify potential regulatory mechanisms associated with basal cell apoptosis in OLP, we investigated the expression of CD40, CD40 ligand (CD40L), CD44 and epithelial (E)-cadherin. METHODS: Biopsies from 22 patients with OLP were investigated by immunohistochemistry for detection of CD40, CD40L, E-cadherin, CD44, Laminin-5 and Collagen IV, double-labelling for CD40 and CD3, and in situ mRNA hybridization for CD40 and CD40L. RESULTS: In actively diseased areas of OLP lesions, basal keratinocytes did not express CD40 and were focally E-cadherin-negative, in contrast to non-diseased areas and normal oral mucosa. Demonstration of intraepithelial T cells expressing CD40 and CD40L, indicates a potential role in inflammatory cell responses involved in the disease process of OLP. CONCLUSION: T cells may orchestrate inflammatory cell responses in OLP via CD40-CD40L interactions. As basal keratinocytes downregulate CD40, they may escape CD40-CD40L-induced apoptosis in OLP. On the other hand, loss of E-cadherin expression may contribute to epithelial basal cell destruction and T-cell migration into the epithelial compartment in OLP.     

Axl基因在口腔鳞状细胞癌中的表达及意义

目的检测Axl(Anexelekto)在口腔鳞状细胞癌中的表达,探索Axl与口腔鳞状细胞癌发生、发展的关系。方法免疫组织化学法(IHC)检测42例口腔鳞状细胞癌患者的癌组织(口腔癌组)及其相应的癌旁组织(癌旁组)Axl的表达状况。原代培养正常人口腔上皮细胞(HOEC),并培养1株永生化正常口腔角化上皮细胞系(NOK)及2株人舌鳞状细胞癌细胞系(UM1、UM2)。实时荧光定量聚合酶链反应(qRT-PCR)和蛋白免疫印迹分析(Western blot)检测上述4种细胞中的Axl的mRNA和蛋白的表达情况。结果 Axl在口腔鳞状细胞癌组织中的阳性表达率(61.9%)高于其相应的癌旁正常组织(26.2%),差异具有统计学意义(P<0.05),qRT-PCR和Western blot结果示在HOEC、NOK、UM2、UM1中Axl基因的mRNA表达和蛋白表达逐步增高,且在UM2、UM1中明显高于HOEC、NOK。结论 Axl在口腔癌组织及口腔癌细胞株中的表达较口腔正常组织和正常口腔上皮细胞者中高表达,提示Axl基因可能与口腔鳞状细胞癌的发生、发展相关。     

Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma – evidence for COX-2 induction by areca quid ingredients in oral keratinocytes

BACKGROUND: Elevated expression of cyclooxygenase (COX)-2 has been demonstrated in several human cancers. Whether COX-2 is up-regulated in areca quid (AQ) related oral squamous cell carcinoma (OSCC) is unknown and the potential of AQ ingredients to induce COX-2 expression has not been studied. METHODS: COX-2 expression was analyzed by immunohistochemistry and RT-PCR in oral tissues. The COX-2 mRNA and protein induction potential of AQ ingredients were analyzed by real-time RT-PCR and Western blotting in normal human oral keratinocyte (NHOK). RESULTS: COX-2 protein expression was significantly higher (P < 0.01) in OSCC (n = 27) as compared to their adjacent non-cancerous matched tissue (NCMT). COX-2 protein was nearly undetectable in control normal oral mucosa. The level of COX-2 mRNA was markedly elevated in 63% (12/19) of OSCC compared to NCMT. Hydroxychavicol induced COX-2 mRNA and protein expression in NHOK. CONCLUSIONS: COX-2 protein as well as mRNA expression were significantly enhanced in OSCC as compared to NCMT. Hydroxychavicol, a unique ingredient in AQ, induced COX-2 expression in NHOK, which highlighted early involvement of COX-2 in AQ-associated oral oncogenesis.     

Osteopontin (OPN) distribution in premalignant and malignant lesions of oral epithelium and expression in cell lines derived from squamous cell carcinoma of the oral cavity

The objectives of this study were to assess the immunolocalization of human osteopontin (OPN) in oral lesions and to identify human cell lines of oral squamous cell carcinoma (OSCC) origin that express OPN mRNA. OPN was localized using immunohistochemistry in the following oral specimens: normal epithelium (n=6), epithelial hyperplasia (n=4), epithelial dysplasia (n=28), carcinoma in situ (n=11) and squamous cell carcinoma (n=43). Cell lines UMSCC-1, MDA TU 138, MDA 686LN, SCC4, SCC9, SCC25, CAL 27 and MDA 1483 were characterized for OPN mRNA expression using Northern blotting. OPN was not detected in normal oral epithelium. Intracellular and intercellular immunore-activity was seen in 75% of hyperplasias, 57% of dysplasias, 54% of carcinoma in situ and 67% of squamous cell carcinomas. UMSCC-1 expressed high levels of OPN mRNA. We conclude that OPN protein is detectable in premalignant and malignant lesions arising from oral epithelium. UMSCC-1 may be a useful cell line in which to conduct in vitro studies designed to clarify the role of OPN in OSCC.     

Expression of p16 in oral cancer and premalignant lesions

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.
Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.
Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.
Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.     

Distribution and synthesis of type VII collagen in oral squamous cell carcinoma

The distribution of the basement membrane anchoring fibril component type VII collagen was studied in oral squamous cell carcinoma by using in situ hybridization and immunohistochemical methods. The expression of type VII collagen in oral normal mucosa, lichen planus and epithelial dysplasias was also investigated. In squamous cell carcinomas, the signals for type VII collagen raRNA were Socated exclusively in malignant peripheral cells in tumour islands and in fibro-blast-like cells among the stromal tissue. In normal buccal mucosa, type VII collagen mRNA expression was located in basal epithelial cells. In oral lichen planus and epithelial dysplasias, the signals for type VII collagen mRNA were also located in basal keratinocytes: however, the signal was especially strong in some epithelial cells. In oral squamous cell carcinomas, the linear immunohistochemical staining pattern of type VII collagen was noted surrounding partly squamous epithelial tumour cell islands, and a large number of tumour cells showed a cytoplasmic staining reaction using the type VII collagen antibody. Some fibroblast-like stromal cells also showed a positive immunostaining reaction. In conclusion, the results of this study indicate that a high synthesis level, but an impaired distribution of type VII collagen, are highly characteristic of squamous epithelial tumour cells.     

CD133在口腔扁平苔藓和口腔鳞状细胞癌中的表达及其临床意义

目的探究肿瘤干细胞标记物CD133在口腔正常黏膜、口腔扁平苔藓（OLP）及口腔鳞状细胞癌（OSCC）中的表达情况及临床意义,评估其作为OLP恶性转化的早期诊断指标、OSCC治疗干预靶标的临床价值,为进一步研究口腔黏膜癌变机制提供基础。 方法回顾性分析10例正常口腔黏膜、60例OLP、60例OSCC患者的临床资料,运用免疫组织化学技术检测各组病理组织中CD133表达情况,采用Mann-Whiney秩和检验比较各组间CD133表达差异,卡方检验统计分析CD133与各临床因素的关系。采用免疫组织化学技术和免疫印迹技术检测人口腔癌前病变细胞株（DOK）和人OSCC细胞株（CAL-27）中CD133的表达情况,t检验比较CD133在DOK与CAL-27细胞株中含量差异。 结果口腔正常黏膜、OLP、OSCC三组中,CD133的阳性率为0（0/10）、31.67%（19/60）、63.33%（38/60）,表达逐渐增强。CD133在口腔正常黏膜与OLP表达强度差异有统计学意义（Z=-2.046,P= 0.041）。CD133在OLP与OSCC表达强度差异具有统计学意义（Z=-3.777,P<0.001）。CD133在DOK中弱阳性表达,在CAL-27中阳性表达,DOK与CAL-27中CD133含量差异有统计学意义（t=-5.029,P= 0.001）CD133与OSCC的临床分期和淋巴结转移有关。 结论CD133作为评估OLP恶性转化潜能的指标及OSCC早期治疗干预靶标可能具有重要临床价值。     

Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma

J Oral Pathol Med (2010) 39 : 368–375 Background: Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously. Methods: To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan–Meier’s test. Results: Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients. Conclusions: These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC.     

The effect of cyclosporin on cell division and apoptosis in human oral keratinocytes

BACKGROUND AND OBJECTIVE: Gingival overgrowth (GO) is a side-effect of cyclosporin A (CsA) therapy and is characterised by enlargement of the gingiva with epithelial thickening and overproduction of extracellular matrix components. The pathogenesis of the epithelial thickening in GO remains obscure. The objective of the present study was to investigate the effects of CsA on the growth of oral epithelial cells in vitro and to test the hypothesis that CsA influences apoptosis in these cells. MATERIAL AND METHODS: Cyclosporin was cocultured with an immortalized normal human oral keratinocyte cell line (HOK-16B), an epitheloid cervical carcinoma cell line (HeLa) and primary oral keratinocytes. Cell division was quantified using a CyQUANT kit. Apoptosis was induced using tumour necrosis factor-alpha (TNF-alpha) and assayed by analysis of caspase-3 activity. Expression of the anti-apoptotic protein, Bcl-2, was measured by western blotting. RESULTS: CsA exhibited a dose- and time-dependent inhibition of cell division in all three keratinocyte cell cultures. Significantly, HOK-16B cells treated with high doses of CsA (10 alphag/ml) did not recover their proliferative capacity 3 d after withdrawal of CsA, indicating that CsA-induced inhibition of growth is not temporary. Concentrations of CsA that inhibited cell division (1 microg/ml) did not have any effect on constitutive or TNF-alpha -induced apoptosis or Bcl-2 expression in HOK-16B cells. CONCLUSION: CsA inhibits oral epithelial cell division and this effect is not associated with changes in apoptosis in these cells. The action of CsA on oral epithelial cells may be associated with a long-lasting stress signal, which might account for some of the pathological effects of this drug.     

Characteristics of a cancerous cell line, HIOEC-B(a)P-96, induced by benzo(a)pyrene from human immortalized oral epithelial cell line

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial region. The mechanism of carcinogenesis of OSCC is still unclear. In vitro study on OSCC cell lines, especially derived from immortalized oral epithelial cells, is a very useful strategy to understand the mechanism of carcinogenesis. Based on our previous human immortalized oral epithelial cell (HIOEC) line, obtained from normal oral epithelial cells by transfection of HPV16 E6/E7 gene, a new cancerous cell line, HIOEC-B(a)P-96 (HB96), was established from the HIOEC by induction with benzo(a)pyrene. The characteristics of the HB96 cells such as cell morphology, ultrastructure, proliferation ability, invasion ability, and tumorigenesis were studied. The HB96 cells lost contact inhibition with uncontrolled cell division and obvious cell overlap, they were polygonal in shape and ununiform in size with increased ratio between nucleus and plasma. Increased proliferative ability and invasion ability were confirmed by the cell proliferation analysis and cell invasion assay, respectively. The tumorigenicity of well to moderately differentiated squamous cell carcinoma was confirmed in the nude mice experiments pathologically. Increased expression of HPV16 E6/E7 proteins and obvious correlation with decreased expression of p53 and Rb proteins was also confirmed by Western blotting. Thus, this HB96 cell line induced by benzo(a)pyrene from the HIOEC line is a useful tool to study the mechanism of carcinogenesis of OSCC in vitro for future genomic and proteomic analyses. It is also the first in vitro cancerous cell line of OSCC in China derived from immortalized oral epithelial cells.     

Aberrant expression of Smad4, a TGF-beta signaling molecule, in oral squamous cell carcinoma

Although carcinogenesis of oral squamous cell carcinoma (OSCC) has been studied by many investigators in the past decade, the available evidence about its molecular mechanism is inconclusive. The objective of the present study was to compare expression of Smad4, a signaling molecule of the transforming growth factor beta (TGF-beta) pathway, between OSCC and normal oral mucosa. We assayed expression of Smad4 in OSCC and normal oral mucosa by performing immunohistochemistry using paraffin-embedded tissue samples. We also compared expression of Smad4 protein between OSCC lines and normal oral keratinocytes, using Western blot analysis. Smad4 expression was observed in only 60% of OSCC tissue samples, whereas it was observed in 82% of normal oral mucosa samples. Reduced Smad4 expression was clearly observed in all OSCC lines, compared with normal oral keratinocytes. These findings suggest that aberration of the TGF-beta pathway, as indicated by a reduction or absence of Smad4 expression, promotes carcinogenesis of OSCC.     

Immunohistochemical evaluation of Fhit protein expression in oral squamous cell carcinomas

The expression of Fhit (fragile histidine triad) protein in oral squamous cell carcinoma (OSCC) and adjacent oral epithelium was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded blocks of 32 cases of OSCC. Rabbit polyclonal anti-GST-Fhit antiserum at 1:600 was used, after antigen enhancement in a microwave pressure cooker, in a saturated lead thiocyanate solution. This antiserum has been shown specifically to detect human Fhit by immunohistochemistry at dilutions up to 1:10,000. The Fhit protein expression was evaluated using both the intensity and extent of staining. Normal stratified squamous epithelium showed strong positivity, especially in the stratum spinosum and areas of keratinisation. Basal and parabasal cells were negative or expressed low levels of Fhit relative to the squamous epithelium. Mild and moderate epithelial dysplasia showed Fhit expression in the superficial layers, while Fhit expression was absent from severely dysplastic lesions. A reduction or loss of Fhit expression was found in 21 (66%) of the OSCC. The alterations in Fhit protein expression in OSCC, and not in normal tissues, are consistent with the proposal that Fhit inactivation plays a role in oral carcinogenesis.     

XIAP、XAF1在口腔鳞癌癌周角质形成细胞中的表达与定位

目的：明确人口腔鳞癌癌周角质形成细胞中XIAP与XAF1的表达与定位情况。方法：对人口腔鳞癌癌周角质形成细胞进行体外培养,间接免疫荧光染色结合激光共聚焦显微镜检测细胞中XIAP和XAF1蛋白的表达与亚细胞定位。结果：XIAP在口腔鳞癌癌周角质形成细胞中呈强阳性表达,胞浆和胞核均有分布,以胞核荧光染色更强。而XAF1主要分布于细胞核内,尤以核膜和核仁染色较强。结论：在口腔黏膜癌变过程中XIAP可能通过过度表达和亚细胞定位的变化而发挥重要的抗凋亡作用,而XAF1表达强度未发生明显变化,不能有效拮抗XIAP的作用。     

口腔鳞状细胞癌中趋化因子受体CCR7的表达及其与颈部淋巴结转移的关系

目的 探讨趋化因子受体CCR7在口腔鳞状细胞癌中的表达及在口腔鳞癌颈淋巴结定向转移中的作用.方法 应用免疫组化、反转录聚合酶链反应(RT-PCR)和Western blotting等方法检测85例口腔鳞状细胞癌组织以及口腔鳞癌细胞系Tca8113和腺样囊性癌细胞系(adenoid cysticcareinoma,ACC-M)中CCR7的表达,分析CCR7表达与口腔鳞癌临床病理参数之间的关系.比较Tca8113和ACC-M对淋巴结的黏附能力,以及CCR7抗体对其黏附能力的影响.结果 66%(56/85)的口腔鳞癌组织存在CCR7的阳性表达,其中淋巴结转移组的CCR7阳性表达率明显高于无淋巴结转移组(P=0.015).RT-PCR和Western blotting检测结果也证实,CCR7在口腔鳞癌中有阳性表达.Tca8113细胞系对淋巴结的黏附能力明显高于ACC-M细胞系,并且能够被CCR7抗体有效阻断.结论 趋化因子受体CCR7在口腔鳞癌的发生发展及淋巴结转移中起着重要的作用.     

血管细胞粘附分子-1在口腔鳞状细胞癌中的表达及其与血管生成的关系

目的 观察口腔鳞状细胞癌组织中血管细胞粘附分子-1（vascular cell adhesion molecule-1，VCAM-1）的表达与定位及其与微血管密度（microvessel density，MVD）间的关系，探讨VCAM-1在口腔鳞状细胞癌血管生成中的意义。方法 用免疫组化二步法检测48例口腔鳞状细胞癌组织和10例正常口腔粘膜组织中VCAM-1和CD31表达并计数微血管密度（MVD）。结果 VCAM-1蛋白主要定位于肿瘤细胞的胞膜和胞浆以及血管内皮细胞；VCAM-1在口腔鳞状细胞癌组织中的表达率显著高于正常口腔粘膜组织（P〈0．01）；口腔鳞状细胞癌组织的MVD值显著高于正常口腔粘膜组织（P〈0．01），MVD值与肿瘤浸润深度和有无淋巴结转移密切相关（P〈0．01）；VCAM-1表达阳性组MVD值显著高于VCAM-1表达阴性组（P〈0．01），且VCAM-1表达与MVD呈正相关（P〈0．01）。结论 VCAM-1在口腔鳞状细胞癌组织中的高表达可能在肿瘤的浸润和转移中起重要作用，并与肿瘤血管生成有关。     

Identity of TUNEL-positive cells in the oral buccal epithelium of normal mucosa and lichen lesions

BACKGROUND: In situ detection of DNA fragmentation by TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick end labeling (TUNEL) is a widely used technique to identify apoptotic cells in the terminal phases of cell death. Several studies have shown that there are statistically increased numbers of TUNEL(+) cells within the epithelium of oral lichen (OL). It was suggested that this indicates an increased rate of apoptosis among basal and suprabasal keratinocytes in OL epithelium. The aim of this study was to identify the TUNEL(+) cells in the epithelium of erythematous (ERY) OL and normal oral mucosa (NOM). METHODS: Sections of biopsies from NOM and ERY OL were processed for TUNEL combined with immunostaining for pan-cytokeratin or for cell markers specifically expressed by different leukocytes. RESULTS: In NOM, TUNEL(+) keratinocytes were almost exclusively seen in the outermost epithelial layers. This labeling was absent in ERY OL. In the basal and lower spinous layers, more TUNEL(+) cell nuclei were seen in ERY OL as compared with NOM, in accordance with previous studies. The present observations show, however, that only very few of these cells were keratinocytes, but rather were CD4(+) lymphocytes and CD68(+) macrophages. There was no difference between the numbers of TUNEL(+) keratinocytes in basal and lower spinous layers in ERY OL and NOM epithelium. No intraepithelial CD8(+) lymphocytes, Langerhans cells, or mast cells were found to be TUNEL(+). CONCLUSION: The findings indicate that the pathologic changes in ERY OL epithelium cannot be explained by increased prevalence of terminal keratinocyte cell death identified by TUNEL.     

Immunohistological evaluation of Ki-67, p63, CK19 and p53 expression in oral epithelial dysplasias

BACKGROUND: Oral squamous cell carcinoma develops through a multistep of genetic mutations, and the process can be morphologically recognized as oral epithelial dysplasia. To evaluate the hypothesis that distributional alterations of proliferating and stem cells may be a useful index to estimate the grading and development of epithelial dysplasia, we examined the distribution patterns according to stratified cell layers. METHODS: Sixty-two oral dysplasia cases according to the histological grades were immunohistologically examined and the nuclear expression of Ki-67 and p63 antigens was counted according to epithelial layers as labeling index. RESULTS: The Ki-67 labeling index in the basal and suprabasal layers and that of p63 in the basal layer showed a significant difference between low- and high-grade groups of epithelial dysplasia. CONCLUSION: The architectural alteration of proliferating cell and stem cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of oral epithelial dysplasias.     

VEGF、EGFR、p16在唇癌与口腔鳞癌中的表达及临床意义

目的 检测血管内皮生长因子（vascular endothelial factor,VEGF)、表皮生长因子受体（epidermal growth for receptor,ERFR)及p16在唇癌及口腔鳞癌组织中的表达分布特征，探讨其在癌发生发展中的作用及临床病理意义，为唇癌及口腔鳞癌的抗血管生成治疗提供临床病理学依据。方法 应用免疫组化LSAB法检测69例唇癌及口腔鳞癌组织中VEGF、EGFR，p16蛋白的表达及变化。结果 唇癌及口腔鳞癌VEGF、EGFR,p16蛋白表达率分别为71．01％、46．37％及28．98％。不同部位唇癌及口腔鳞癌组织间VEGF、GEFR、p16阳性表达率差异无显著性（P＞0．05）；VEGF在唇癌及口腔鳞癌与非瘤组织中的阳性表达率分别为71．01％、10．00％，二者差异有显著性（P＜0．05）；VEGF、EGFR、p16在唇癌及口腔癌组织中的阳性表达无明显相关（P＞0．05）。结论 唇癌及口腔鳞癌组织中VEGF、EGFRp16之间蛋白表达无相关；VEGF在非瘤组织与唇癌及口腔鳞癌中的表达率差异有显著性；VEGF在唇癌及口腔鳞癌发生发展中起重要作用，可作为有用的标志物。     

Immunohistochemical evaluation of expression of cytokeratin 19 in different histological grades of leukoplakia and oral squamous cell carcinoma.

Recent progress in understanding the biology of keratins together with the development of monoclonal antibodies to individual keratin proteins provide the foundation for studying the keratin expression in normal and pathological oral epithelia. Cytokeratin (CK) alterations have been reported in carcinomas and these have been associated with specific aspects of tumour behaviour. Immunohisto-chemistry with monospecific CK19 antibody was used to study the expression pattern in normal mucosa, dysplasias, and oral squamous cell carcinomas (OSCC). In non-keratinzed normal mucosa, CK19 was detected in the basal cell layer, while in dysplasias (diagnosed in H and E stained sections, mild-severe) stained strongly for CK 19 in the basal and supra basal cell layers indicating layer specificity for CK 19 expression. In OSCC, in the number of CK19 labelled cells increased from well to poorly differentiated tumour. Thus the results of the present study indicate an alteration in synthesis of keratin proteins when exposed to carcinogens.