Biomedical subjects

Chen Liu

Publications and source records attributed to Chen Liu.

At least 37 records · Page 2Linked to original sources

PubMed2006

[Breast reconstruction with a combined skin flap of DIEP and TRAM].

OBJECTIVE: To evaluate breast reconstruction with a combined skin flap of the deep inferior epigastric perforator (DIEP) and the transverse rectus abdominis musculocutaneous (TRAM). METHODS: The DIEP and TRAM united flap was elevated with the vessel pedicle of the deep inferior epigastric perforator on the affected side and the rectus abdominis muscle pedicle on the intact side. The reconstructive breast was shaped after the deep inferior epigastric vessels were anastomosed to the internal mammary vessels or the thoracodorsal vessels ipsilaterally. RESULTS: We have used the DIEP and TRAM united flaps for breast reconstruction in 17 cases. All of the flaps survived, and the reconstructed breasts were well-shaped with the follow-up of 6-18 months. CONCLUSIONS: The DIEP and TRAM united flap possesses of advantages such as rich blood supply, abundant tissue volume and easy shaping. It is especially applicable to the cases who have large chest defect and need large volume tissue.

Adult↗

PubMed2006

[Sarcolemmal sodium-calcium exchanger mediated the beneficial effects of myocardial ischemic preconditioning and pharmacological preconditioning].

OBJECTIVE: To investigate the role of sodium-calcium exchanger (NCX) on ischemic preconditioning and pharmacological preconditioning. METHODS: Cultured rat neonatal cardiomyocytes were randomly divided into 6 groups: (1) ischemia/reperfusion group (9 h ischemia followed by 1 h reperfusion, I/R), (2) ischemic preconditioning group (1.5 h ischemia/1 h reperfusion + I/R), (3) pharmacologic preconditioning group, adenosine (10 micromol/L) pretreated for 1 h + I/R, (4) calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (0.5 micromol/L for 0.5 h) + ischemic preconditioning group, (5) KN-93 + pharmacologic preconditioning group, (6) control group. The leakage of intracellular lactate dehydrogenase (LDH) in various groups was determined by biochemical autoanalyzer. Semi-quantitative RT-PCR was employed to measure the mRNA levels of sodium-calcium exchanger. Activity of sodium-calcium exchanger (Na(+)-dependent (45)Ca(2+) uptake) was measured by liquid scintillation counting. RESULTS: (1) Compared to the I/R group, the LDH leakages in both ischemic preconditioning group and pharmacologic preconditioning group were significantly reduced (P < 0.05) while significantly increased in the KN-93 + pharmacologic preconditioning group and the KN-93 + ischemic preconditioning group (P < 0.05). (2) The Na(+)-dependent (45)Ca(2+) uptake was significantly increased in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05). (3) The expression of NCX mRNA in I/R group was also significantly increased (P < 0.05) in the I/R group (P < 0.05) compared to control group and this increase could be significantly attenuated in ischemic preconditioning group and adenosine pretreatment group (P < 0.05), CaMKII inhibitor KN-93 significantly abolished these effects in preconditioning group (P < 0.05) and in adenosine pretreated group (P < 0.05). CONCLUSION: NCX mediated the cardioprotective effects of ischemic preconditioning and pharmacological preconditioning in the neonatal cardiomyocytes I/R model.

Animals↗

PubMed2006

Presentation and management of gastrointestinal stromal tumors of the duodenum.

Duodenal gastrointestinal stromal tumors (GIST) have been described primarily in isolated case reports. In order to learn more about duodenal GIST, a retrospective review of patients with GIST managed at a single institution between 2000 and 2005 was conducted. Thirty-eight GIST of the stomach and small bowel were analyzed. Eight (21%) were duodenal GIST. The median size of duodenal GIST (6.0 cm) and small bowel GIST (6.3 cm) was larger than the median size of gastric GIST (3.0 cm). The most common presentation of duodenal GIST was bleeding (50%) which was similar to other small bowel GIST (49%) but different from gastric GIST which were most commonly an incidental finding (62%). Two patients (25%) with duodenal GIST had a history of neurofibromatosis. The duodenal GIST were located in the 2nd (n = 5, 63%) and 3rd portion of duodenum (n = 3, 37%). Seven of 8 patients underwent complete resection of duodenal GIST. Pancreaticoduodenectomy was the most common operation performed (n = 5); 2 patients were treated with partial duodenal resection. No patients undergoing pancreaticoduodenectomy (n = 5) were found to have lymph node metastases. No patients received neo-adjuvant or adjuvant therapy with Imatinib. Following resection, 2 patients have recurred (12 and 48 mo.), 4 patients are without disease (1, 6, 6, and 24 mo.), 1 patient died postoperatively. Duodenal GIST are relatively rare tumors that present most commonly with gastrointestinal bleeding. Duodenal GIST are associated with neurofibromatosis. Many duodenal GIST require pancreaticoduodenectomy for complete removal.

Adult↗

PubMed2006

[Construction and utilization of the prognostic model of serous ovarian adenocarcinoma].

OBJECTIVE: To analyze the related factors with prognosis in patients with serous ovarian adenocarcinoma and to set up a prognostic model of serous ovarian adenocarcinoma. METHODS: The clinical, pathological and follow-up data of 104 cases with serous ovarian adenocarcinoma were retrospectively analyzed. Kaplan-meier univariate analysis was used to screen the prognostic factors; COX univariate and multivariate analyses were used to determine the risk coefficient of each factors and different layers in each factor. Pearson rank correlation was used to reject the influence of different factors with each other. And the prognostic model of serous ovarian adenocarcinoma was set up based on the result of the above study, which could be used to deduce the survival probability of patients with serous ovarian adenocarcinoma. RESULTS: International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.0029), histological grade (P = 0.0054), residual disease (P = 0.0000), metastasis of lymph nodes (P = 0.0000) and chemotherapy (P = 0.0000) were the related factors of prognosis in patients with serous ovarian adenocarcinoma, of which FIGO stage was the most important one, followed sequentially by histological grade, metastasis of lymph node, residual disease and chemotherapy (the independent risk coefficient of each factor was 1.3392, 0.9206, 0.7071, 0.6004, 0.4985 in sequence). We set up a prognosis model according to the prognostic index of each factors. The effect of chemotherapy and residual disease on prognosis could be quantified by this model, and the higher the score, the lower the survival probability of patients. CONCLUSIONS: FIGO stage, histological grade, residual disease, metastasis of lymph nodes and chemotherapy are important prognostic factors of serous ovarian adenocarcinoma. This model can be used to estimate the prognosis of patients with serous ovarian adenocarcinoma, and the effect of both chemotherapy and residual disease on the prognosis could be quantified by the model.

Adult↗

PubMed2005

Absence of beta7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine.

The alpha4beta7 integrin plays a central role in the homing of T cells to the gut. We hypothesized that absence of the beta7 subunit would result in a reduction of intestinal graft-versus-host disease (GVHD) and an improvement in overall GVHD morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT). Analysis of alloreactive beta7-/- T cells showed intact activation, proliferation, cytokine production, and cytotoxicity. However, recipients of beta7-/- donor T cells in murine HSCT models experienced less GVHD morbidity and mortality than recipients of wild-type (WT) T cells, associated with a decrease in donor T-cell infiltration of the liver and intestine and with an overall significant decrease in hepatic and intestinal GVHD. In graft-versus-tumor (GVT) experiments, we demonstrated intact or even enhanced GVT activity of beta7-/- donor T cells. In conclusion, beta7-/- donor T cells caused less GVHD morbidity and mortality than WT donor T cells because of selectively decreased T-cell infiltration of the liver and intestines. Our data suggest that strategies to target the beta7 integrin have the clinical potential to alleviate or prevent GVHD while sparing or potentiating GVT activity.

Animals↗

PubMed2005

A crucial role for antigen-presenting cells and alloantigen expression in graft-versus-leukemia responses.

Graft-versus-leukemia (GVL) response after allogeneic bone marrow transplantation (BMT) represents one of the most potent forms of immunotherapy against malignant diseases. Antigen-presenting cells (APCs) are crucial for the induction of graft-versus-host disease (GVHD), the most serious complication of allogeneic BMT, but their role in GVL responses is unclear. Using a series of clinically relevant mouse GVL tumor models, we found that APCs and alloantigen expression on tumors are crucial for GVL. Moreover, APCs of host origin predominated in GVL responses although donor APCs contributed as the acuity of tumor burden decreased.

Animals↗

PubMed2005

Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication.

Interferon alpha (IFN-alpha)-based therapy is the currently approved treatment for chronic hepatitis C viral infection. The sustained antiviral response rate is approximately 50% for genotype-1 infection. The major challenge to the HCV community is to improve antiviral efficacy and to reduce the side effects typically seen in IFNalpha-based therapy. One of the strategies is to identify new interferons, which may have better efficacy and less undesirable side effects. In this report, we examined the role of IL-28A (IFN lambda2), a novel type I IFN, in suppression of human hepatitis C viral RNA replication. We have cloned both the human genomic DNA and cDNA of IL-28A, and evaluated their biological activity using HCV RNA replicon cell culture system. The results show that IL-28A effectively inhibits HCV subgenomic RNA replication in a dose-dependent manner. Treatment of human hepatoma cells with IL-28A activates the JAK-STAT signaling pathway and induces the expression of some interferon-stimulated genes (ISGs), such as 6-16 and 1-8U. We also demonstrate that IL-28A induces expression of HLA class I antigens in human hepatoma cells. Moreover, IL-28A appears to specifically suppress HCV IRES-mediated translation. Although IL-28A receptor shares one subunit with the IL-10 receptor, IL-10 treatment has no detectable effect on IL-28A-induced antiviral activity. Interestingly, IL-28A can synergistically enhance IFNalpha antiviral efficacy. Our results suggest that IL-28A antiviral activity is associated with the activation of the JAK-STAT signaling pathway and expression of ISGs. The effectiveness of IL-28A antiviral activity and its synergistic effect on IFN-alpha indicate that IL-28A may be potentially used to treat HCV chronic infection.

Animals↗

PubMed2005

CCR2 is required for CD8-induced graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Migration of donor-derived T cells into GVHD target organs plays a critical role in the development of GVHD and chemokines and their receptors are important molecules involved in this process. Here, we demonstrate in murine bone marrow transplantation models that the expression of the inflammatory CC chemokine receptor 2 (CCR2) on donor-derived CD8+ T cells is relevant for the control of CD8+ T-cell migration and development of GVHD. Recipients of CCR2-deficient (CCR2-/-) CD8+ T cells developed less damage of gut and liver than recipients of wild-type CD8+ T cells, which correlated with a reduction in overall GVHD morbidity and mortality. Assessment of donor CD8+ T-cell target organ infiltration revealed that CCR2-/- CD8+ T cells have an intrinsic migratory defect to the gut and liver. Other causes for the reduction in GVHD could be excluded, as alloreactive proliferation, activation, IFN-gamma production and cytotoxicity of CCR2-/- CD8+ T cells were intact. Interestingly, the graft-versus-tumor effect mediated by CCR2-/- CD8+ T cells was preserved, which suggests that interference with T-cell migration by blockade of CCR2 signaling can separate GVHD from GVT activity.

Animals↗

PubMed2005

Absence of inducible costimulator on alloreactive T cells reduces graft versus host disease and induces Th2 deviation.

Inducible costimulator (ICOS) is expressed on activated and memory T cells and is involved in the regulation of cytokine production. We studied the role of ICOS on alloreactive T cells in graft versus host disease (GVHD) and determined that ICOS expression was up-regulated on alloreactive T cells in recipients of an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with GVHD. We compared ICOS-/- T cells with wild-type (WT) T cells in 2 GVHD models. In both models, recipients of ICOS-/- T cells demonstrated significantly less GVHD morbidity and mortality, which was associated with less intestinal and hepatic GVHD but increased cutaneous GVHD. In addition, recipients of ICOS-/- donor T cells displayed a slight decrease in graft versus leukemia (GVL) activity. Further analysis of alloreactive ICOS-/- T cells showed no defect in activation, proliferation, cytotoxicity, and target organ infiltration. Recipients of ICOS-/- T cells had decreased serum levels of interferon-gamma (IFN-gamma), while interleukin-4 (IL-4) and IL-10 levels were increased, suggesting that alloreactive ICOS-/- T cells are skewed toward T helper-2 (Th2) differentiation. These data suggest a novel role for ICOS in the regulation of Th1/Th2 development of activated T cells. In conclusion, alloreactive ICOS-/- donor T cells induce less GVHD due to a Th2 immune deviation while GVL activity is slightly diminished.

Animals↗

PubMed2005

Interventional endovascular treatment for Budd-Chiari syndrome with long-term follow-up.

PURPOSE: To present results of a 9 year followup of percutaneous transluminal angioplasty (PTA) and stents placement in patients with Budd-Chiari Syndrome (BCS) and to evaluate the clinical value and applicability of this approach. MATERIALS AND METHODS: 44 consecutive patients with BCS (25 male and 19 female; average age, 42.6 years; age range, 19-77 years) were treated with PTA and stents during a 9-year period. The mean duration of symptoms was 46 months. Underlying active malignancy was the cause of occlusion in 5 patients. 3 patients had a history of taking oral contraceptives. The obstructed inferior vena cava (IVC) or hepatic vein (HV) were first dilated by a percutaneous transluminal balloon, and then a self-expanding stent was placed. Clinical patency was defined as absence or improvement of symptoms. Clinical follow-up was supplemented with colour Doppler sonography, CT scan, or both. RESULTS: Technical success was achieved in 97.2% (35/36) IVC and 83% (10/12) HV PTA and stents. Significantly, the IVC pressure decreased from 2.7 kPa (SD = 0.3) to 1.5 kPa (SD = 0.4) and HV pressure dropped from 2.3 kPa (SD = 0.4) to 1.3 kPa (SD = 0.2). The symptoms and signs disappeared or were relieved after operation in most of the patients. A few serious related complications including one stent migration and one pulmonary emboli occurred and were resolved in time. Patients were followed for a mean of 44 months (range 3-102). Short- and long-term results were satisfactory except for 3 patients (9.4%, 1 IVC, 2 HV) who presented with a restenosis or thrombosis and underwent additional therapy. There were 5 deaths owing to underlying malignant disease 3-17 months after the procedures. CONCLUSION: PTA and stent placements proved a safe and effective treatment in BCS and had a good long-term outcome and should be considered in patients who have symptoms or have no adequate alternative therapy.

Adult↗

PubMed2005

[Eversion carotid endarterectomy for carotid stenosis].

OBJECTIVE: To observe the effect of using eversion carotid endarterectomy (eCEA) for carotid stenosis. METHODS: Twenty four patients with carotid stenosis (stenosis grade 65% approximately 95%), of which 18 were symptomatic and 6 were asymptomatic, were treated by eCEA under regional anesthesia. All patients underwent preoperative cervical duplex and DSA, CT or MRA scanning examination. The eversion technique involved an oblique transection of the internal carotid artery at the carotid bulb and a subsequent endarterectomy by everting the internal carotid artery over the atheromatous plaque. RESULTS: There was no perioperative mortality and stroke. Transient ischemic attacks (TIA) disappeared, cerebral ischemia symptom improved in our patients. But there were mini chronic symptom of cerebral ischemia in 4 patients with both carotid arterial stenosis. CONCLUSION: Carotid eversion endarterectomy appears to be a universally applicable, safe, and durable operative technique.

Aged↗

PubMed2005

Critical role of host gammadelta T cells in experimental acute graft-versus-host disease.

Gammadelta T cells localize to target tissues of graft-versus-host disease (GVHD) and therefore we investigated the role of host gammadelta T cells in the pathogenesis of acute GVHD in several well-characterized allogeneic bone marrow transplantation (BMT) models. Depletion of host gammadelta T cells in wild-type (wt) B6 recipients by administration of anti-T-cell receptor (TCR) gammadelta monoclonal antibody reduced GVHD, and gammadelta T-cell-deficient (gammadelta-/-) BM transplant recipients experienced markedly improved survival compared with normal controls (63% vs 10%, P < .001). gammadelta T cells were responsible for this difference because reconstitution of gammadelta-/- recipients with gammadelta T cells restored GVHD mortality. gammadelta-/- recipients showed decreased serum levels of tumor necrosis factor alpha (TNF-alpha), less GVHD histopathologic damage, and reduced donor T-cell expansion. Mechanistic analysis of this phenomenon demonstrated that dendritic cells (DCs) from gammadelta-/- recipients exhibited less allostimulatory capacity compared to wt DCs after irradiation. Normal DCs derived from BM caused greater allogeneic T-cell proliferation when cocultured with gammadelta T cells than DCs cocultured with medium alone. This enhancement did not depend on interferon gamma (IFN-gamma), TNF-alpha, or CD40 ligand but did depend on cell-to-cell contact. These data demonstrated that the host gammadelta T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen-presenting cells.

Acute Disease↗

PubMed2005

A role for CD54 (intercellular adhesion molecule-1) in leukocyte recruitment to the lung during the development of experimental idiopathic pneumonia syndrome.

BACKGROUND: Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication of allogeneic bone marrow transplantation (BMT). IPS is associated with elevated bronchoalveolar lavage (BAL) fluid levels of tumor necrosis factor-alpha and lipopolysaccharide, both of which are potent activators of endothelial cells (ECs). EC expression of the adhesion molecule CD54 (intercellular adhesion molecule [ICAM]-1) has been shown to be a major regulator of pulmonary inflammation in various experimental models. METHODS: Using a well-established murine BMT system in which lung injury and graft-versus-host disease (GvHD) are induced by minor histocompatibility antigenic differences between donor and host, the RNase Protection Assay, mice deficient in ICAM-1 expression, and a monoclonal blocking antibody to ICAM, we evaluated the role of the pulmonary vascular expression of CD54 in the development of IPS. RESULTS: Enhanced pulmonary vascular expression of ICAM-1 coincided with the development of IPS. When ICAM-1 -/- mice were used as allogeneic BMT recipients, IPS severity (measured by lung histopathology, BAL cellularity, and cytokine expression) was significantly reduced compared with wild-type controls. Similar results were also observed when wild-type recipients were treated with a monoclonal blocking antibody to ICAM-1. Surprisingly, ICAM-1 had differential effects on leukocyte infiltration into GvHD target organs; ICAM-1 deficiency had no impact on intestinal histopathology, whereas ICAM-1-/- BMT recipients had significantly enhanced hepatic injury. CONCLUSIONS: These data demonstrate that although the expression of ICAM-1 is critical for the development of IPS, different mechanisms of leukocyte recruitment are operative in other GvHD target organs.

Animals↗

PubMed2005

Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells.

NKT cells are a unique immunoregulatory T cell population that produces large amounts of cytokines. We have investigated whether stimulation of host NKT cells could modulate acute graft-vs-host disease (GVHD) in mice. Injection of the synthetic NKT cell ligand alpha-galactosylceramide (alpha-GalCer) to recipient mice on day 0 following allogeneic bone marrow transplantation promoted Th2 polarization of donor T cells and a dramatic reduction of serum TNF-alpha, a critical mediator of GVHD. A single injection of alpha-GalCer to recipient mice significantly reduced morbidity and mortality of GVHD. However, the same treatment was unable to confer protection against GVHD in NKT cell-deficient CD1d knockout (CD1d(-/-)) or IL-4(-/-) recipient mice or when STAT6(-/-) mice were used as donors, indicating the critical role of host NKT cells, host production of IL-4, and Th2 cytokine responses mediated by donor T cells on the protective effects of alpha-GalCer against GVHD. Thus, stimulation of host NKT cells through administration of NKT ligand can regulate acute GVHD by inducing Th2 polarization of donor T cells via STAT6-dependent mechanisms and might represent a novel strategy for prevention of acute GVHD.

Animals↗

PubMed2005

Association of genetic polymorphism in GH gene with milk production traits in Beijing Holstein cows.

Associations were analysed between polymorphisms of the growth hormone gene (GH-MspI) (localized in intron 3) and milk production traits of Beijing Holstein cows (a total of 543 cows). Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used for identification of various genotypes. Frequencies of genotypes were 0.77, 0.21 and 0.02 for A/A, A/B and B/B, respectively. The frequency of the GH A allele is 0.875. The results of the least squares means show that in all three lactations, the GH A/A cows yielded more milk (P less than 0.01 for lactation I and P less than 0.05 for lactations II and III), whereas A/B cows showed higher milk fat content than A/A individuals (P less than 0.05 for lactations I and II, and P less than 0.01 for lactation III). The A/A cows yielded more fat than A/B individuals (P less than 0.01 only in lactation I). The A/A cows yielded more milk protein than A/B individuals (P less than 0.01 for lactations I, II, and III). The A/A cows produced milk of higher protein content than of A/B individuals (P less than 0.05 only in lactation II).

Animals↗

PubMed2005

Impact of humoral immune response on distribution and efficacy of recombinant adeno-associated virus-derived acid alpha-glucosidase in a model of glycogen storage disease type II.

Glycogen storage disease type II (GSDII) is a lysosomal storage disease caused by a deficiency in acid alpha-glucosidase (GAA), and leads to cardiorespiratory failure by the age of 2 years. In this study, we investigate the impact of anti-GAA antibody formation on cross-correction of the heart, diaphragm, and hind-limb muscles from liver-directed delivery of recombinant adeno-associated virus (rAAV)5- and rAAV8-GAA vectors. GAA(-/-) mice receiving 1 x 10(12) vector genomes of rAAV5- or rAAV8-DHBV-hGAA were analyzed for anti-GAA antibody response, GAA levels, glycogen reduction, and contractile function. We demonstrate that restoration of GAA to the affected muscles is dependent on the presence or absence of the antibody response. Immune-tolerant mice had significantly increased enzyme levels in the heart and skeletal muscles, whereas immune-responsive mice had background levels of GAA in all tissues except the diaphragm. The increased levels of activity in immune-tolerant mice correlated with reduced glycogen in the heart and diaphragm and, overall, contractile function of the soleus muscle was significantly improved. These findings highlight the importance of the immune response to rAAV-encoded GAA in correcting GSDII and provide additional understanding of the approach to treatment of GSDII.

Animals↗

PubMed2005

Defective Jak-Stat activation in hepatoma cells is associated with hepatitis C viral IFN-alpha resistance.

Interferon-alpha (IFN-alpha) has been widely used to treat viral infections and certain types of cancers. Large numbers of patients with chronic hepatitis C viral (HCV) infection do not respond to IFN and ribavirin combination therapy, and the majority of patients do not respond to IFN monotherapy. The underlying mechanisms of HCV nonresponse to IFN are unknown. In this report, using a HCV subgenomic replicon cell culture system, we show that (1) long-term IFN stimulation can select cells defective for Stat3 activation, and the defect appears to be responsible for HCV IFN resistance in cell culture, (2) HCV subgenomic sequence mutations associated with long-term culture do not appear to be responsible for IFN resistance, (3) expression of the activated Stat3 reverses IFN resistance while a dominant negative form of Stat3 renders an IFN-sensitive cell line resistant to IFN, and (4) the IFN-resistant cell line exhibits enhanced suppressor of cytokine signaling 3 (SOCS3) expression in response to IFN stimulation, and blocking SOCS3 in the IFN-resistant cell line partially restores IFN sensitivity. These findings strongly suggest that the IFN-resistant phenotype in vitro is associated with defective Stat3 activation and an enhanced SOCS3 response but is not associated with viral sequence mutations. Our study implies that long-term IFN stimulation in vitro selects cells that exhibit alterations in the host Jak-Stat signaling pathway, thereby representing a potential mechanism by which HCV resists IFN therapy.

Antiviral Agents↗

PubMed2005

Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.

OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. The purpose of this study was to investigate the functional properties of VIN related to expression of p16(INK4a) protein as well as to detection of human papillomavirus (HPV) type 16 by real-time polymerase chain reaction (RT-PCR) analysis. METHODS: A total of 49 vulvar biopsy samples were examined by hematoxylin-eosin staining from benign/reactive lesions, condyloma acuminatum, VIN, and invasive squamous cell carcinoma (SCC). JC8 mouse monoclonal antibodies were used that recognize p16(INK4a) epitope at a dilution of 1:25. The reaction pattern for p16(INK4a) was graded in each sample between 0 and 3+. RT-PCR analysis of formalin-fixed paraffin-embedded sections determined positivity for HPV type 16. RESULTS: p16(INK4a) immunoreactivity was different in VIN 1, VIN 2, VIN 3, and squamous cell carcinoma. Strong expression of p16(INK4a) protein was observed in 92% (22 of 24) of VIN 2 and VIN 3 lesions and 100% (4 of 4) of invasive SCCs. Two (67%) of 3 VIN 2 lesions, 17 (81%) of 21 VIN 3 lesions, and 4 (100%) of 4 SCCs were positive for HPV type 16 by PCR analysis. Two (20%) of 10 VIN 1 lesions were immunoreactive for p16(INK4a), with only 1 lesion positive for HPV type 16. No p16(INK4a) immunoreactivity was observed in any of the benign/reactive and condyloma acuminatum lesions. In addition, none of the benign/reactive or condyloma lesions were positive for HPV type 16 by RT-PCR analysis. CONCLUSIONS: Upregulation of INK4a gene occurs in vulvar carcinogenesis. p16(INK4a) is not a sensitive marker for differentiation of benign vulvar squamous epithelium from condyloma acuminatum or VIN 1 lesions because most VIN 1 lesions are p16(INK4a) negative. Expression of p16(INK4a) may aid in the diagnosis of HPV-related lesions and as such may be of value as a surrogate marker in the diagnosis of vulvar premalignant and malignant lesions.

Adult↗