Predictability in Diabetic Nephropathy

ABSTRACT Possible association between several variables and the prognosis of nephropathy was investigated in 23 insulin-dependent diabetics with established diabetic nephropathy. Age at onset and duration of diabetes, blood pressure and metabolic control were among these variables. In the mean observation period of 27 months, end-stage renal disease (ESRD) developed in 11 patients. Nine patients died, including six with progression to ESRD, mainly of cardiac disease. Age, duration of diabetes, insulin requirement, blood pressure and glycosylated hemoglobin concentration showed higher values in the patients with progression to ESRD, but no difference was statistically significant. During the observation time, however, blood pressure was less well controlled in the patients who developed ESRD. The deterioration rate of renal function showed wide interindividual variation. In each patient, however, the decline seemed to follow a linear regression course. The results suggest that, in the absence of dependable prognostic factors, regular individual monitoring of glomerular filtration rate can provide a reliable predictive estimate of the progression rate.     

肾素-血管紧张素系统与血管再生的研究进展

肾素-血管紧张素系统在维持水、电解质平衡及血压方面起重要作用,近年来随着对肾素-血管紧张素系统认识的加深,发现肾素-血管紧张素系统不仅参与高血压,心肌梗死,心力衰竭等疾病的病理生理过程,还可通过影响血管内皮生长因子从而在血管再生方面起重要的调节作用。现就肾素-血管紧张素系统在血管再生方面的作用做一综述。     

Constant Glomerular Filtration Rate in Diabetic Nephropathy

ABSTRACT. Twenty-one patients with diabetes of type I and diabetic nephropathy with reduced glomerular filtration rate (GFR) were followed prospectively with regard to GFR, proteinuria, blood pressure and glucosylated haemoglobin (HbA₁). All patients were on antihypertensive treatment. The mean rate of decline in GFR was only 0.38 ml/month = 4.6 ml/year. In one third of the patients, GFR remained constant at a reduced level for at least 24 months. Mean plasma clearance of ⁵¹Cr-EDTA in this group was 48.3±14.6 ml/min/1.73 m² body surface at entry and 48.0±13.6 at the time of evaluation. The patients with constant GFR had significantly less proteinuria and lower systolic as well as mean arterial pressure during the study than patients with falling GFR. They also had significantly lower mean HbA₁ and fewer very high HbA₁ values than patients who deteriorated. The data thus indicate that a combination of good metabolic control and effective blood pressure control may strongly delay the progression of renal insufficiency in diabetic nephropathy. They also show that low degree of proteinuria is a marker of good prognosis.     

Rethinking the Renin-Angiotensin System and Its Role in Cardiovascular Regulation

Angiotensin-converting enzyme (ACE) plays a pivotal role in the renin-angiotensin system (RAS) and ACE-inhibitors are widely used in several clinical conditions, including hypertension and heart failure. Recently, a homologue of ACE, ACE₂ has been discovered. Both ACE and ACE₂ are emerging as key enzymes of the RAS, where ACE₂ may play a role as negative regulator of ACE. Moreover, ACE₂ appears to be an important enzyme outside the classical RAS, as it hydrolyzes apelins, dynorphin A 1-13, des-Arg-bradykinin and other peptide substrates. The precise interplay between tissue ACE, ACE₂, and their substrates and by-products are presently still unclear.ACE-inhibitors reduce angiotensin II formation and bradykinin degradation, but do not inhibit ACE₂ activity. Moreover, ACE-inhibitors differ in their affinity for tissue ACE, and it has been suggested that tissue ACE affinity might be responsible for some of the beneficial properties of these drugs. ACE-inhibitors also increase nitric oxide availability, and activate several kinases that may regulate protein synthesis by interacting with the nucleus of the cells (outside-in signaling). The outside-in signaling may also be activated by bradykinin itself. Although, the precise significance of the outside-in signaling is still unclear, this new role of ACE-inhibitors may represent a discriminant factor versus angiotensin II receptors antagonists.This mini review will summarize some new aspects concerning the recently discovered biological functions of RAS and in particular of ACE, ACE₂ and ACE-inhibitors in cardiovascular system.     

Renal function after intravitreal administration of vascular endothelial growth factor inhibitors in patients with diabetes and chronic kidney disease

The present study aimed to determine whether intravitreal administration of vascular endothelial growth factor inhibitors is associated with deterioration of renal function, as seen with systemic administration, in patients with diabetes and chronic kidney disease. Estimated glomerular filtration rates before and after 160 intravitreal injections of vascular endothelial growth factor inhibitors (aflibercept, bevacizumab or ranibizumab) were compared in 69 patients with diabetes and with a baseline estimated glomerular filtration rate <60 mL/min/1.73 m². We also determined the incidence of acute kidney injury. The data showed no significant difference in the estimated glomerular filtration rate before and after vascular endothelial growth factor inhibitor administration in all patients and in patient subgroups based on each inhibitor. Furthermore, no episodes of acute kidney injury occurred. In conclusion, intravitreal administration of vascular endothelial growth factor inhibitors is unlikely to be associated with a deterioration of renal function in patients with diabetes and chronic kidney disease.     

Metabolic and Blood Pressure Monitoring in Diabetic Renal Failure

ABSTRACT. In a prospective study of eight patients with type I diabetic renal failure, metabolic and blood pressure monitoring was evaluated during progression to end-stage renal disease (ESRD). The mean observation time was 37 months. The mean glomerular filtration rate (GFR) fell significantly (from 33 to 16 ml/min) implying a mean deterioration rate of 0.57 ml/min/month. This rate showed significant correlation with mean arterial blood pressure at out-patient observations, but not with blood glucose monitored as 24-hour profile or with glycosylated hemoglobin. Patients with growth hormone values within the upper limit of the normal range showed faster decline of GFR than patients with low values. The study demonstrated that advanced diabetic renal failure may progress slowly to ESRD. The blood pressure pattern, but not blood glucose values, influenced significantly the deterioration rate of glomerular function.     

Angiotensin converting enzyme inhibition reduces retinal overexpression of vascular endothelial growth factor and hyperpermeability in experimental diabetes

Aims/hypothesis. Angiotensin converting enzyme (ACE) inhibition has been recently suggested to have retinoprotective actions in diabetic patients but the mechanism of this effect is not known. In vitro, angiotensin II stimulates expression of vascular endothelial growth factor (VEGF), a permeability-inducing and endothelial cell specific angiogenic factor which has been implicated in the pathogenesis of diabetic retinopathy in humans and in experimental animals. We sought to determine the effects of ACE inhibition on retinal VEGF expression and permeability in experimental diabetic retinopathy.¶Methods. Streptozotocin-induced diabetic rats and control animals were assigned at random to receive ACE inhibitor treatment or vehicle. At 24 weeks the retinal VEGF protein gene expression was assessed by northern blot analysis and in situ hybridisation. Retinal permeability to albumin was measured using a double isotope technique.¶Results. Experimental diabetes was associated with cell specific two to fourfold increase in retinal VEGF protein gene expression (p < 0.01) and a 2-fold increase in retinal vascular permeability to albumin (p < 0.01). The localization of VEGF expression in the retina was not altered in animals with experimental diabetes. Angiotensin converting enzyme inhibitor treatment of diabetic rats reduced diabetes-associated changes in VEGF gene expression and vascular permeability.¶Conclusion/interpretation. These findings implicate the renin-angiotensin system in the VEGF overexpression and hyperpermeability which accompany diabetic retinopathy and provide a potential mechanism for the beneficial effects of ACE inhibition in diabetic retinal disease. [Diabetologia (2000) 43: 1360–1367]     

Regression of left ventricular hypertrophy and improvement of renal hemodynamics in hypertensive patients treated with quinapril

Summary Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174.7±16.7 to 131.7±7.7 mmHg (p<.0001) and diastolic pressure decreased from 101.8±9.8 to 80±4.3 mmHg (p<.0001). Left ventricular mass index decreased in the eight patients with left ventricular hypertrophy (p<.01). Basal values of GFR were lower than normal in 41% of all patients; GFR increased significantly after 20 weeks of treatment (from 96.5±32.3 to 108.6±31.12 ml/min, p<.01); it decreased in only one patient. Patients reported few adverse effects to quinapril, and no important clinical laboratory abnormality was observed. Quinapril not only lowered arterial pressure, but it had a distinct effect on regression of left ventricular hypertrophy and favorable effects on renal function.     

Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in Type 2 diabetes mellitus.

AIMS: Vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of diabetes mellitus. We determined whether alterations of plasma and urinary VEGF levels are related to diabetic nephropathy in Type 2 diabetic patients. METHODS: One hundred and seven patients and 47 healthy controls were studied. Study subjects were divided into four groups using urinary albumin-to-creatinine ratio (ACR): a non-diabetic healthy control group (n = 47), a normoalbuminuric diabetic group (n = 37), a microalbuminuric diabetic group (n = 37) and an overt proteinuric diabetic group (n = 33). VEGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: (i) Urinary VEGF concentrations were significantly higher in the diabetic groups, even at the normoalbuminuric stage (log VEGF/Cr, normoalbuminuria; 4.33 +/- 1.06 vs. control; 3.53 +/- 0.79, P = 0.009). Urinary VEGF excretions increased as diabetic nephropathy advanced. (ii) Plasma and urinary VEGF levels were higher in hypertensive diabetic patients than in the normotensive individuals with diabetes. (iii) In those with diabetes, plasma VEGF levels were found to be positively correlated with plasma urea (r = 0.398, P = 0.039) and urinary ACR (r = 0.251, P = 0.044), and urinary VEGF to be positively correlated with urinary ACR (r = 0.645, P < 0.001), and creatinine (r = 0.336, P = 0.009), and to be negatively correlated with serum albumin (r = -0.557, P < 0.001). Urinary VEGF and serum creatinine were independently correlated with urinary ACR. CONCLUSIONS: Urinary excretion of VEGF increased during the earlier stage of diabetic nephropathy and was significantly correlated with urinary albumin excretion. This suggests that urinary VEGF might be used as a sensitive marker of diabetic nephropathy and for predicting disease progression.     

Blood pressure early in diabetes depends on a balance between glomerular filtration rate and the renin-angiotensin system

Onset of diabetes increases plasma renin activity (PRA) and glomerular filtration rate (GFR), but blood pressure (BP) is normal. In this study, a 70% surgical reduction in kidney mass (RK) was used to decrease baseline GFR and to prevent hyperfiltration during diabetes, and angiotensin converting enzyme inhibitors (ACEI) were used to inhibit angiotensin II (AngII) production, to test the hypothesis that a balance between GFR and AngII is required for normal BP early in diabetes. Diabetes was induced with streptozotocin (STZ) (35 mg/kg intravenously); and after 7 days of hyperglycemia (range: 408 to 486 mg/dL), insulin was intravenously infused continuously for a 4-day normoglycemic recovery period. In normal kidney (NK) rats, diabetes increased PRA (2.4 +/- 0.6 to 4.6 +/- 0.5 ngAI/mL/h) and GFR (2.9 +/- 0.1 to 3.5 +/- 0.2 mL/min), and there was no change in mean arterial pressure (MAP) (89 +/- 1 v 91 +/- 1 mm Hg, measured 18 h/day). There was no change in either GFR or AngII during diabetes in RK+ACEI rats, and their MAP also did not change. Thus, the maintenance of normal MAP was accompanied by a balance between GFR and AngII in both of those groups. In NK+ACEI rats, however, GFR increased significantly with no change in AngII, and MAP decreased significantly during diabetes by approximately 8 mm Hg. In RK rats, PRA increased (0.5 +/- 0.1 to 2.6 +/- 0.5) but GFR did not increase, and MAP increased significantly by approximately 16 mm Hg. All rats were in sodium balance by day 4 of diabetes. These data support the hypothesis that normotension early in diabetes requires a balance between the increased AngII and GFR, and that BP will increase if AngII increases but GFR does not.     

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy

Summary Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mmHg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 g/min (geometric mean 688 g/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml·min^–1· (1.73 m²)^–1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open+occluded) was estimated by combined light- and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r=0.77, p<10^–4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r=-0.78, p<10^–5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects.Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.     

VEGF与VEGF-C蛋白在胆管癌中的表达及意义

目的探讨VEGF与VEGF-C蛋白在胆管癌的表达及其与临床病理特征的关系。方法采用免疫组化SP法检测49例胆管癌组织中vEGF与VEGF-C叠白的表达。结果胆管癌VEGF和VEGF—C蛋白的表达率分别为65．3％和69．4％。VEGF和VEGF-C蛋白的高表达与胆管癌淋巴结转移及分化程度有关。VEGF与VEGF—C的表达有显著相关性（P＜0．01）。结论VEGF和VEGF—C蛋白的表达与胆管癌侵袭转移有关。     

Severe Diabetic Nephropathy in Type 1 Diabetes and Pregnancy - A Case Series

BACKGROUND: Diabetes and nephropathy are important challenges during pregnancy, increasingly encountered because of the advances in maternal-fetal care. AIM: To evaluate the maternal and fetal outcomes recorded in "severe" diabetic nephropathy in type 1 diabetic patients referred to nephrological healtcare. METHODS: The study was performed in an outpatient unit dedicated to kidney diseases in pregnancy (with joint nephrological and obstetric follow-up and strict cooperation with the diabetes unit). 383 pregnancies were referred to the outpatient unit in 2000-2012, 14 of which were complicated by type 1 diabetes. The report includes 12 deliveries, including 2 pregnancies in 1 patient; one twin pregnancy; 2 spontaneous abortions were not included. All cases had long-standing type 1 diabetes (median of 21 (15-31) years), relatively high median age (35 (29-40) years) and end-organ damage (all patients presented laser-treated retinopathy and half of them clinical neuropathy). Median glomerular filtration rate (GFR) at referral was 67 ml/min (48-122.6), proteinuria was 1.6 g/day (0.1-6.3 g/day). RESULTS: Proteinuria steeply increased in 11/12 patients, reaching the nephrotic range in nine (6 above 5 g/day). One patient increased by 2 chronic kidney disease (CKD) stages. Support therapy included blood pressure and diabetes control, bed rest, and moderate protein restriction. All children were preterm (7 early preterm); early spontaneous labor occurred in 4/12 patients. All singletons were appropriate for gestational age and developed normally after birth. The male twin child died 6 days after birth (after surgery for great vessel transposition). CONCLUSIONS: Diabetic patients with severe diabetic nephropathy are still present a considerable challenge. Therefore, further investigations are required, particularly on proteinuria management and the occurrence of spontaneous labor.     

原发性高血压患者ACE2基因G8790A多态性与心房颤动的相关性研究

目的:探讨中国河南豫北地区原发性高血压人群血管紧张素转化酶2(ACE2)基因G8790A多态性与心房颤动(Af)的关系。方法:运用病例-对照法,选择953例原发性高血压患者,运用PCR-RFLP对其中475例伴Af(Af组)和478例窦性心律者(非Af组)的ACE2基因G8790A多态性进行基因分型及分析。结果:ACE2基因G8790A等位基因G在男性中的频率:Af组157例(72.0%),非Af组100例(59.5%),差异有统计学意义(P<0.05);在女性中的频率:Af组291例(56.6%),非Af组280例(45.2%),差异有统计学意义(P<0.05)。携带等位基因G的高血压男、女患者发生Af的危险性均增加(OR:1.82,95%CI:1.15～3.07;OR:1.99,95%CI:1.29～5.01,P<0.05)。基因型AA、AG和GG在Af组女性的频率分别为47例(18.3%)、130例(50.6%)和80例(31.1%),在非Af组分别为98例(31.6%)、136例(43.9%)、76例(24.5%),两组基因型分布差异有统计学意义(P<0.05)。与AA基因型相比,携带GG基因型的女性原发性高血压患者发生Af危险性增加(OR=2.05,95%CI:1.390～3.403),男性携带G等位基因和女性携带GG基因型的高血压并发Af患者左心房内径明显增大(P<0.05),女性携带GG基因型者左心室射血分数明显降低(P<0.05)。结论:ACE2基因G8790A多态性与原发性高血压患者Af的发生存在相关性,男女性携带G等位基因和女性携带GG基因型可能使原发性高血压发生Af的危险性增加。     

Peripheral vascular disease in Type 2 diabetic Chinese patients: associations with metabolic indices, concomitant vascular disease and genetic factors.

AIMS: Conventional and genetic risk factors have been reported to play a role in the pathogenesis of vascular disease, but do not explain the lower burden of cardiac and peripheral vascular disease (PVD) in Chinese compared with Caucasians. The role of renin-angiotensin system (RAS) gene polymorphisms and conventional vascular risk factors has not been determined. METHODS: A total of 3097 Chinese diabetic subjects were screened for PVD, which was identified in 194 of the 2967 patients with Type 2 diabetes. Biochemical parameters and the genotype and allele frequencies of three RAS gene polymorphisms, the angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms were then compared between the PVD patients and 1046 age, gender and diabetes duration-matched patients without PVD. RESULTS: PVD identified in 6.5% was associated with significantly worse glycaemic control, lipid profile and renal function. Smoking was more common, as were the other macro- and microvascular diseases. The prevalence of hypertension was similar between the groups, yet diastolic blood pressure was slightly lower in the PVD group. The ACE D allele was significantly more frequent in patients with PVD compared with the matched diabetic controls (38.1 vs. 29.8%, P = 0.039). No differences in the AT1R or AGT polymorphisms were observed. CONCLUSIONS: PVD was associated with a worse metabolic profile and greater concomitant vascular disease than controls. The ACE I/D polymorphism was associated with PVD in these Type 2 diabetic patients.     

Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators

OBJECTIVE: The goal of these studies was to define the anatomic pathways by which circulating macromolecules extravasate from the hyperpermeable microvessels that supply tumors and from normal venules that have been rendered hyperpermeable by vasoactive mediators. METHODS: Extravasation pathways of circulating macromolecular tracers were followed by several morphological techniques: light and fluorescence microscopy, transmission electron microscopy of routine as well as ultrathin and serial sections, computer-assisted three-dimensional reconstructions, and morphometry. RESULTS AND DISCUSSION: Macromolecules extravasated across tumor microvessels or across normal venules rendered hyperpermeable by VPF/VEGF, histamine, or serotonin by three primary pathways: 1) Vesiculo-vacuolar organelles (VVOs), clusters of cytoplasmic vesicles and vacuoles that span endothelial cytoplasm from lumen to ablumen; 2) trans-endothelial cell (EC), pores, and 3) fenestrae. We also present data concerning the structure and function of VVOs as well as evidence that VVOs form as the result of linking together and fusion of caveolae-sized unit vesicles. Under suitable conditions VVOs also afforded a pathway for macromolecular transport in the reverse direction, i.e., from vascular ablumen to lumen. Finally, in addition to opening VVOs to the passage of macromolecules, mediators such as VPF/VEGF may also induce structural rearrangements of VVOs, transforming them into trans-EC pores or fenestrae.     

Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease

The development of diabetic nephropathy in patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus is still a huge clinical problem associated with increased morbidity and mortality. The mechanisms underlying the development of diabetic kidney disease are extremely complex and yet not completely understood. Among many potential pathogenic mechanisms responsible for the development of diabetic kidney disease, various growth factors have been suggested to be important players. In particular, growth hormone (GH)/insulin-like growth factors (IGFs), transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) have measurable effects on the development of experimental diabetic kidney disease through complex intra-renal systems. Recent findings that these growth factors might initiate the early diabetic renal changes have provided insight into processes that might be relevant for future development of new drugs useful in the treatment of diabetic kidney disease. As will appear from the present review, enhanced understanding of the cellular mechanisms responsible for the development of diabetic kidney disease has already allowed the design of specific antagonists of pathophysiologically increased growth factors. Recent studies have shown that treating experimental diabetic models with such antagonists is followed by renoprotection. [Diabetologia (2000) 43: 1205–1223]     

Dabrafenib- and trametinib-associated glomerular toxicity: A case report

Rationale:Combined treatment with dabrafenib, a B-RAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, is an effective option for patients with metastatic melanoma. A few cases of acute kidney injury associated with tubulointerstitial nephritis and 1 case of nephrotic syndrome have been reported in patients on this drug combination; however, progressive renal injury has not been reported. In this case study, we report a patient with metastatic melanoma who developed glomerular capillary endothelial toxicity and progressive glomerular sclerosis during combination therapy.Patient concern:Our patient was an 80-year-old woman with a history of type 2 diabetes and chronic kidney disease.Diagnosis and intervention:She was diagnosed with metastatic melanoma and commenced combination therapy with dabrafenib and trametinib.Outcomes:Her renal function progressively deteriorated; by month 20 after treatment commencement, her serum creatinine level had increased from 1.59 to 3.74 mg/dL. The first kidney biopsy revealed marked glomerular and endothelial cell damage. Her medication was stopped, but no improvement was evident. At 5 months after the first biopsy, her serum creatinine level had increased to 5.46 mg/dL; a second kidney biopsy revealed focal segmental glomerular sclerosis and marked tubulointerstitial fibrosis. She was started on hemodialysis.Lessons:We describe a patient with a metastatic melanoma who developed progressive kidney failure during treatment with dabrafenib and trametinib. The most prominent microscopy findings were glomerular endothelial damage in the initial kidney biopsy and accelerated glomerular sclerosis and tubulointerstitial fibrosis in the follow-up biopsy. We hypothesize that a decreased renal reserve and impairment of kidney repair capacity caused by inhibition of B-RAF, a downstream mediator of vascular endothelial growth factor, may explain the progressive kidney injury.     

喉癌组织中VEGF-C及其受体VEGFR-3和D2-40的表达及意义

目的 观察血管内皮生长因子C（VEGF-C）及其受体（VEGFR-3）和D2-40在喉癌组织中的表达情况,探讨其在喉癌淋巴道转移过程中的作用及可能机制.方法 选择喉癌患者的癌组织、癌旁正常组织标本各40份,同期选择正常喉组织标本19份作对照.采用免疫组织化学法检测各标本中VEGF-C、VEGFR-3和D240的表达.结果 VEGF-C、VEGFR-3及D2-40在喉癌组织、癌旁组织及正常喉组织中均有表达,且其表达强度呈下降趋势（H分别为38.400、32.502,P均＜0.01）;在喉癌组织中,VEGF-C、VEGFR-3及D2-40的表达与淋巴转移、临床分期及临床分型有关（P均＜0.05）,与病理分级、肿瘤大小、吸烟量、年龄和性别无关（P均＞0.05）.喉癌组织中VEGF-C与VEGFRd的表达呈正相关（r=0.882,P＜0.01）.结论 VEGF-C、VEGFR-3及D2-40在喉癌组织中的表达均明显高于癌旁组织及正常喉组织,其高表达可能与喉癌的发生、发展有关.