Portable real-time colorimetric LAMP-device for rapid quantitative detection of nucleic acids in crude samples.

Loop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting-substances. In this work, we developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative analysis with the simplicity of point-of-care testing. The device innovation lies on the use of a plastic tube anchored vertically on a hot surface while the side walls are exposed to a mini camera able to take snapshots of the colour change in real time during LAMP amplification. Competitive features are the rapid analysis (< 30 min), quantification over 9 log-units, crude sample-compatibility (saliva, tissue, swabs), low detection limit (< 5 copies/reaction), smartphone-operation, fast prototyping (3D-printing) and ability to select the dye of interest (Phenol red, HNB). The device's clinical utility is demonstrated in cancer mutations-analysis during the detection of 0.01% of BRAF-V600E-to-wild-type molecules from tissue samples and COVID-19 testing with 97% (Ct < 36.8) and 98% (Ct < 30) sensitivity when using extracted RNA and nasopharyngeal-swabs, respectively. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.

Canine hepacivirus is not associated with chronic liver disease in dogs.

Canine hepacivirus (CHV) has recently been identified in liver and respiratory tract samples from dogs, and comparative phylogenetic analysis has confirmed it to be the closest genetic relative of hepatitis C virus (HCV) described to date. CHV offers great potential as a model system for HCV, but only if the underlying processes of infection and pathogenesis are similar for both viruses. However, it is not yet clear if CHV is hepatotrophic. Canine chronic hepatitis (CH) is a common and usually idiopathic disease that shares similar histological features to that of HCV infection of humans. To date, no study has attempted to determine whether CHV is involved in the aetiology of liver disease in dogs. We employed two nested PCR assays, using primers targeting regions of the helicase domain of CHV NS3, to identify viral nucleic acids in liver samples from 100 dogs with CH of unknown cause in the UK. We also used a sensitive luciferase immunoprecipitation system (LIPS) assay to screen serum samples from these dogs for the presence of anti-CHV antibodies. Surprisingly, there was no evidence of exposure to, or a carrier state of, CHV in this large cohort, suggesting that the virus is not associated with CH in UK dogs. Future work, including transmission studies, is required to understand the pathogenesis of CHV in canids before it can be proposed as a surrogate model for HCV-induced liver disease in man.

Electrical property sensing biopsy needle for prostate cancer detection.

BACKGROUND: Significant electrical property differences have been demonstrated to exist between malignant and benign prostate tissues. We evaluated how well a custom designed clinically deployable electrical property sensing biopsy needle is able to discriminate between these tissue types in an ex vivo prostate model. METHODS: An electrical impedance spectroscopy (EIS) sensing biopsy (Bx) needle was developed to record resistive (ρR) and reactive (ρX) components of electrical impedance from 100 Hz to 1 MHz. Standard twelve-core biopsy protocols were followed, in which the EIS-Bx device was used to gauge electrical properties prior to extracting tissue cores through biopsy needle firing from 36 ex vivo human prostates. Histopathological assessment of the cores was statistically compared to the impedance spectrum gauged from each core. RESULTS: The magnitudes of the mean resistive and reactive components were significantly higher in cancer tissues (P < 0.05). ROC curves showed that ρR at 63.09 kHz was optimal for discriminating cancer from benign tissues; this parameter had 75.4% specificity, 76.1% sensitivity, and ROC AUC of 0.779. Similarly, 251.1 kHz was optimal when using ρX to discriminate cancer from benign tissues; this parameter had a 77.9% specificity, 71.4% sensitivity, and ROC AUC of 0.79. CONCLUSION: Significant electrical property differences noted between benign and malignant prostate tissues suggest the potential efficacy an EIS-Bx device would provide for cancer detection in a clinical setting. By sensing a greater fraction of the prostate's volume in real-time, the EIS-Bx device has the potential to improve the accuracy of cancer grading and volume estimation made with current biopsy procedures.

A real-time electrical impedance sensing biopsy needle.

Diagnostic confirmation of cancer in solid organs is based on biopsy findings. In a standard 12-core prostate biopsy protocol, conventional biopsy needles sample only 0.95% (∼0.228 cm³) of a typical 24-cm³ prostate gland. The primary objective of this study was to enhance the sensitivity of standard biopsy protocol by gauging electrical properties of tissue simultaneously with tissue extraction for histopathology analysis. A conventional biopsy (Bx) needle was instrumented with an electrical impedance spectroscopy (EIS) sensor to interrogate the tissue volume surrounding the needle tip. The EIS-Bx device was evaluated in a series of saline bath and ex vivo porcine experiments. It was found to sense a volume of 0.286 cm³ of tissue around the needle tip. EIS measurements were recorded from three ex vivo human prostates using the device, and the extracted biopsy cores were histologically assessed. Prostate conductivity σ ranged from 0.179 to 0.3310 S/m for benign tissues and 0.0746 to 0.0837 S/m for malignant tissues at frequencies ranging from 1 to 100 kHz. Relative permittivity ϵ(r) ranged from 2.10×106 to 2.9 × 104 for benign and 6.63×105 to 5.3 × 10³ for cancer tissues over the same frequency range. Both are found to be significantly higher in normal prostate tissues than in malignant tissue (p < 0.00001).

Electrical impedance spectroscopy for prostate cancer diagnosis.

Electrical impedance was recorded at 21 discrete frequencies (1 to 100 kHz) from 27 ex vivo human prostates. These electrical properties were measured by using custom designed Electrical Impedance Spectroscopy (EIS) sensing biopsy (Bx) needles. EIS-Bx needles gauge the electrical properties of tissue in tandem with the tissue extraction (used for histopathological assessment). The EIS-Bx probe has a signal-to-noise ratio (SNR) of 65 dB across the frequency range (1 kHz to 100 kHz). A total of 36 cancers and 288 benign regions were sampled from 27 human prostates. Mean resistance (R) of prostate decreased from 537.27 Ω to 126.74 Ω for benign tissues and 999.52 Ω to 340.67 Ω for malignant tissues across the 1 kHz - 100 kHz spectral range. Likewise, mean reactance (X) ranged from -391.41 Ω to -62.6 Ω for benign and -675.09 Ω to -162.28 Ω for cancer tissues over the same frequency range. Both R and X values are found to be significantly lower in normal prostate tissues than in malignant tissue (p<0.001). Further testing to evaluate the clinical efficacy of this coupled device is underway.

Spontaneous metastasis in mouse models of testicular germ-cell tumours.

Testicular germ-cell tumours (TGCTs) are the most common cancer in young men; the incidence is increasing worldwide and they have an unusually high rate of metastasis. Despite significant work on TGCTs and their metastases in humans, absence of a mouse model of spontaneous metastasis has greatly limited our understanding of the mechanisms by which metastatic potential is acquired and on their modes of dissemination. We report a new model of spontaneous TGCT metastasis in the 129 family of mice and provide evidence that these are true metastases derived directly from primary testicular cancers rather than independently from ectopic stem cells. These putative metastases (pMETs) occur at similar frequencies among TGCT-affected males in six genetically distinct TGCT-susceptible strains and were largely found in anatomical sites that are consistent with patterns of TGCT metastasis in humans. Various lines of evidence support their pluripotency and germ-cell origin, including presence of multiple endodermal, mesodermal and ectodermal derivatives as well as cells showing OCT4 and SSEA-1 pluripotency markers. In addition, pMETs were never found in males that did not have a TGCT, suggesting that metastases are derived from primary tumours. Finally, pMETS and primary TGCTs shared several DNA copy number variants suggesting a common cellular and developmental origin. Together, these results provide the first evidence for spontaneous TGCT metastasis in mice and show that these metastases originate from primary TGCTs rather than independently from ectopic stem cells.

Parity, early menopause and the incidence of bladder cancer in women: a case-control study and meta-analysis.

INTRODUCTION: Incidence rates of bladder cancer are notably higher in men than in women. While there is evidence that reproductive and hormonal risk factors may influence risk of bladder cancer, data are inconclusive. MATERIALS AND METHODS: We examined reproductive, menstrual and hormonal use history in our population-based case-control study of bladder cancer in New Hampshire (NH), USA (n=207 women cases and n=463 women controls). Additionally, we performed a meta-analysis of the published literature. We used unconditional logistic regression analysis to compute adjusted odds ratios associated with each risk factor in the NH study. We combined these estimates with those from the published literature using inverse variance effects models. RESULTS: In the NH study, a slightly decreased odds ratio was found among women who had ever had a birth compared to nulliparous women and an elevated odds ratio among women who underwent surgical menopause (bilateral oophorectomy), especially at an early age. No overall associations were found with oral contraceptive use or hormone replacement therapy. These findings were generally in agreement with the meta-analytic results for which the combined relative risk (RR) estimate was reduced among ever parous women (combined RR estimate for ever parous versus nulliparous=0.66, 95% confidence intervals [95% CI] 0.55-0.79) and elevated among those undergoing an early menopause (combined RR estimate for early versus late menopause=1.59, 95% CI 1.31-1.92). No consistent risk was observed for the other factors. DISCUSSION: Some reproductive and menstrual factors appear to be related to the incidence of bladder cancer among women; but whether effects are due to female hormones is uncertain.

Screening of clinical, food, water and animal isolates of Escherichia coli for the presence of blaCTX-M extended spectrum beta-lactamase (ESBL) antibiotic resistance gene loci.

A small study was carried out in order to examine the molecular presence of bla CTX-M gene phylogenetic groups in E. coli (n=263) isolated from food (n=54), water (n=7), animal sources (n=69), using consensus bla CTX-M primers and PCR, in addition to human faecal isolates (n=69) and VTEC O157:H7 (n=64). None of the clinically significant faecal VTEC O157:H7 isolates were shown to carry blaCTX-M type phylogenetic groups, nor were such phylogenetic groups observed in any of the food, water and animal isolates. One community faecal isolate (1/69; 1.4%), dating from 1997, carried this phylogenetic group. As recent work has indicated that a significant proportion of such phylogenetic groups are carried in community isolates of E. coli with little or no hospital contact, it is important that surveillance is increased to identify potential source(s) and reservoirs of such resistance in the community. Further prospective surveillance is thus required to help elucidate the origins of such phylogenetic group in the community. The significance of this study is that the ESBL-producing E. coli associated with local hospital outbreaks is not commonly found in local food, water or animal sources. In addition, given that ESBL-producing E. coli is now a significant organism, both in hospitals and nursing homes in Northern Ireland, this report demonstrates that such organisms were present in the community, as early as 1997.

Glucocorticoid therapy and risk of bladder cancer.

BACKGROUND: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. METHODS: In a population-based case-control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. RESULTS: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24-2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17-3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26-4.36). CONCLUSION: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology.

Life cycle optimisation for highway best management practices.

Highway runoff can cause a number of water quantity and quality problems. Stormwater management systems for highways have been developed based on a fast drainage for large storm situations. Non-point source pollution from highway runoff is a growing water quality concern. Stormwater quality control needs to be integrated into highway drainage design and operation to reduce the stormwater impacts on the receiving water. A continuous simulation/optimisation model for analysing integrated highway best management practices (BMPs) is presented. This model can evaluate the life cycle performance of infiltration and/or storage oriented highway BMPs. It can be directly integrated with spreadsheet optimisation tools to find the least cost options for implementing BMPs throughout a specified life cycle.

Inhibition of host peripheral blood mononuclear cell proliferation ex vivo by Rinderpest virus.

Rinderpest, or cattle plague, is caused by Rinderpest virus (RPV), which is related most closely to human Measles virus (MV), both being members of the genus Morbillivirus, a group of viruses known to have strong immunosuppressive effects in vitro and in vivo. Here, it was shown that peripheral blood mononuclear cells (PBMCs) isolated from cattle experimentally infected with either wild-type or vaccine strains of RPV impaired the proliferation of PBMCs derived from uninfected animals; however, in contrast to either mild or virulent strains of wild-type virus, the inhibition induced by the vaccine was both weak and transient. Flow-cytometric analysis of PBMCs obtained from cattle infected with different strains of RPV showed that the proportion of infected cells was virus dose-dependent and correlated with lymphoproliferative suppression.

Inhibition of in vitro leukocyte proliferation by morbilliviruses.

Immune suppression associated with morbillivirus infections may influence the mortality rate by allowing secondary bacterial infections that are lethal to the host to flourish. Using an in vitro proliferation assay, we have shown that all members of the genus Morbillivirus inhibit the proliferation of a human B-lymphoblast cell line (BJAB). Proliferation of freshly isolated, stimulated bovine and caprine peripheral blood lymphocytes is also inhibited by UV-inactivated rinderpest (RPV) and peste-des-petits ruminants viruses. As for measles virus, coexpression of both the fusion and the hemagglutinin proteins of RPV is necessary and sufficient to induce immune suppression in vitro.

Self-ratings of materialism and status consumption in a Malaysian sample: effects of answering during an assumed recession versus economic growth.

Consumers' self-assessments of materialism and status consumption may be influenced by external economic conditions. In this study, 239 Malaysian students were asked to describe their levels of materialism using Richins and Dawson's 1992 Materialism scale and status consumption using Eastman, Goldsmith, and Flynn's 1999 Status Consumption Scale. Half the students were told to respond assuming that they were in an expanding economy, and half as if the economy was in a recession. Comparison of the groups' mean scores showed no statistically significant differences.

Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer.

Homologues for human p53 (Hsp53) and p73 (Hsp73) genes were cloned and expression patterns for their corresponding proteins analysed in tissues from normal and leukemic softshell clams (Mya arenaria). These are the first structural and functional data for p53 and p73 cDNAs and gene products in a naturally occurring, non-mammalian disease model. Core sequence of the predicted clam p53 (Map53) and p73 (Map73) proteins is virtually identical and includes the following highly conserved regions: the transcriptional activation domain (TAD), MDM2 binding site, ATM phosphorylation site, proline rich domain, DNA binding domains (DBDs) II-V, nuclear import and export signals and the tetramerization domain. The core sequence is a structural mosaic of the corresponding human proteins, with the TAD and DBDs resembling Hsp53 and Hsp73, respectively. This suggests that Map53 and Map73 proteins may function similarly to human proteins. Clam proteins have either a short (Map53) or long (Map73) C-terminal extension. These features suggest that Map53 and Map73 may be alternate splice variants of a p63/p73-like ancestral gene. Map73 is significantly upregulated in hemocytes and adductor muscle from leukemic clams. In leukemic hemocytes, both proteins are absent from the nucleus and sequestered in the cytoplasm. This observation suggests that a non-mutational p53/p73-dependent mechanism may be involved in the clam disease. Further studies of these gene products in clams may reveal p53/p73-related molecular mechanisms that are held in common with Burkitt's lymphoma or other human cancers.

Phase I pilot trial of the bispecific antibody MDXH210 (anti-Fc gamma RI X anti-HER-2/neu) in patients whose prostate cancer overexpresses HER-2/neu.

The goal of this study was to evaluate, in patients with prostate cancer, the toxicity profile and biologic activity of the bispecific antibody MDXH210, which has specificity for the non-ligand-binding site of the high-affinity immunoglobulin G receptor (Fc gamma RI) and the extracellular domain of the HER-2/neu proto-oncogene product. Patients with prostate cancer that expressed HER-2/neu were entered into a phase I dose-escalation trial of MDXH210. Patients received an intravenous infusion MDXH210 during a period of 2 h three times per week for 2 weeks and were monitored for toxicity. Pharmacokinetic and pharmacodynamic parameters were measured and included the biologic end points of monocyte-bound MDXH210, cytokine production, and clinical response. Seven patients were treated with MDXH210 doses ranging from 1 to 8 mg/m2. In general, MDXH210 was well tolerated, with only mild infusion-related malaise, fever, chills, and myalgias. No dose-limiting toxic effects were observed. Biologic effects included induction of low plasma concentrations of tumor necrosis factor-alpha and interleukin-6 observed immediately after MDXH210 infusion and 70% saturation of circulating monocyte-associated Fc gamma RI with MDXH210 at a dose level of 4 to 8 mg/m2. Five of six patients had stable prostate-specific antigen levels during the course of 40 days or more. Circulating plasma HER-2/neu levels decreased by 80% at days 12 and 29 (p = 0.03 and 0.06, respectively, by the Wilcoxon signed rank test). MDXH210 can be given safely to patients with HER-2/neu-positive prostate cancer in doses of at least 8 mg/m2. At the doses studied, biologic activity was demonstrated and characterized by binding of MDXH210 to circulating monocytes, release of monocyte-derived cytokines, a decrease in circulating HER-2/neu, and short-term stabilization of prostate-specific antigen levels.

A randomized phase II trial comparing two different sequence combinations of autologous vaccine and human recombinant interferon gamma and human recombinant interferon alpha2B therapy in patients with metastatic renal cell carcinoma: clinical outcome and analysis of immunological parameters.

PURPOSE: The clinical observation of spontaneous regression in patients with renal cell carcinoma (RCC) and the response to various immunotherapeutic therapies strongly suggest a role for the host immune system in this disease. Prior studies showed that sequential administration of interferon (IFN) gamma and IFN alpha to RCC patients was safe. Clinical responses as well as immune changes in the peripheral blood mononuclear cell compartment were observed. Autologous tumor cell vaccines (AV) have also demonstrated activity in renal cell carcinoma. We hypothesize that the addition of AV to sequential IFN gamma and a therapy might improve the tumor-specific immune response by providing an appropriate source of antigen in the appropriate cytokine environment. To our knowledge, this is the first trial using AV combined with IFN alpha and IFN gamma. The purpose of this study was to evaluate the feasibility of manufacturing and administering (AV) from resected tumor samples, and administration of AV with combination IFN gamma and IFN alpha therapy. Finally, the impact on immunological parameters of these treatment options was assessed. MATERIALS AND METHODS: Patients with metastatic RCC were randomly assigned to receive AV plus bCG along with a sequential administration of IFN gamma and a either together or after initiation of vaccine. Toxicity and clinical responses were evaluated. Modulations of the immune system were investigated by analyzing phenotype, cytokine mRNA expression, T cell proliferation and cytotoxicity in the peripheral blood mononuclear cell compartment. RESULTS: Fourteen patients with metastatic renal cell carcinoma were enrolled in this study; 9 were available for response evaluation. In a 70 day period, 3 (33%) showed mixed responses, 5 (56%) stable disease and 1 (11%) progression of disease. Toxicities were consistent with previous clinical reports. In the flow-cytometry phenotype analysis, stimulation of distinct subsets of circulating T-lymphocytes and a decrease of CD8+ T cell subsets was demonstrated. T-cell proliferation to allogeneic tumor cell stimulation improved following treatment. IL-4 and IL-5 mRNA levels were reduced in all patients after treatment. Patients who responded to treatment did not produce any IL-4 mRNA at all, before or after treatment. CONCLUSIONS: AV with IFNgamma and IFNalpha therapy might induce a MHC class-mediated cytotoxic T lymphocyte (CTL) response. We suggest that adequate therapy might direct T cell response toward a Th1 type response. We hypothesize a state of improved immune readiness in patients who might eventually respond to immunotherapy.

The effect of hospital volume on mortality and resource use after radical prostatectomy.

PURPOSE: The value of radical prostatectomy for patients with prostate cancer depends on low morbidity and mortality. We assessed whether patient outcome is associated with how many of these procedures are performed at hospitals yearly. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample, which is a stratified probability sample of American hospitals, we identified 66,693 men who underwent radical prostatectomy between 1989 and 1995. Cases were categorized into volume groups according to hospital annual rate of radical prostatectomies performed, including low-fewer than 25, medium-25 to 54 and high-greater than 54. We performed multivariate logistic regression to control for patient characteristics when assessing the associations of hospital volume, in-hospital mortality and resource use. RESULTS: Overall adjusted in-hospital mortality after radical prostatectomy was relatively low (0.25%). However, patients at low volume centers were 78% more likely to have in-hospital mortality than those at high volume centers (adjusted odds ratio 1.78, 95% confidence interval 1.7 to 2.6). Overall length of stay decreased at all hospitals between 1989 and 1995. However, average length of stay was longer and total hospital charges were higher at low than at high volume centers (7.3 versus 6.1 days, p<0.0001, and $15,600 versus $13,500, p<0.0001, respectively). CONCLUSIONS: Hospital volumes inversely related to in-hospital mortality, length of stay and total hospital charges after radical prostatectomy. Further study is necessary to examine the association of hospital volume with other important outcomes, including incontinence, impotence and long-term patient survival after radical prostatectomy.

Expression, regulation, and function of B cell-expressed CD154 in germinal centers.

Activated B cells and T cells express CD154/CD40 ligand in vitro. The in vivo expression and function of B cell CD154 remain unclear and therefore were examined. Tonsillar B and T cells expressed CD154 at a similar density both in situ and immediately ex vivo, whereas a significantly higher percentage of the former expressed CD154. CD154-expressing B cells were most frequent in the CD38positiveIgD+ pre-germinal center (GC)/GC founder, CD38positive GC and CD38-IgD- memory populations, and were also found in the CD38-IgD+ naive and CD38brightIgD+ plasmablast subsets, but not in the CD38brightIgD- plasma cell subset. B cell expression of CD154 was induced by engaging surface Ig or CD40 by signals that predominantly involved activation of AP-1/NF-AT and NF-kappaB, respectively. The functional importance of CD154-mediated homotypic B cell interactions in vivo was indicated by the finding that mAb to CD154 inhibited differentiation of CD38positiveIgD- GC B cells to CD38-IgD- memory cells. In addition, mAb to CD154 inhibited proliferation induced by engaging sIg or CD40, indicating the role of up-regulation of this molecule in facilitating B cell responsiveness. Of note, CD154 itself not only functioned as a ligand but also as a direct signaling molecule as anti-CD154-conjugated Sepharose beads costimulated B cell responses induced by engaging surface Ig. These results indicate that CD154 is expressed by human B cells in vivo and plays an important role in mediating B cell responses.

Vulvar metastases secondary to transitional cell carcinoma of the bladder. A case report.

BACKGROUND: Gynecologists are frequently asked to evaluate patients with vulvar lesions. Although the differential diagnosis of a vulvar lesion is varied, the main concern is to rule out a vulvar malignancy. Primary vulvar carcinoma is uncommon, and a metastatic cancer from an extragenital site involving the vulva is even more rare. CASE: A 78-year-old woman with a history of a transitional cell carcinoma (TCC) of the bladder presented with two painful vulvar lesions, which represented the first manifestation of metastatic disease. This is the fifth reported case of TCC from the bladder with metastases to the vulva. CONCLUSION: The differential diagnosis of a vulvar lesion, especially in a woman with a prior history of renal tract malignancy, should include metastatic lesions.

In vivo description of dendritic cells in human renal cell carcinoma.

PURPOSE: Dendritic cells (DCs) are efficient and effective antigen-presenting cells that play a major role in initiating the primary immune response. They are the most potent stimulators of T-cell activation and would thus be expected to be of great importance in the antitumoral immune response. Although DC phenotype and function have been described under in vitro conditions, their in vivo characteristics are less well detailed. Human renal cell carcinoma (RCC) is an excellent model to explore tumor infiltrating dendritic cells (TiDCs) because of rare clinical spontaneous regressions and the association of high numbers of tumor infiltrating lymphocytes (TiLs), suggesting a strong immune response. MATERIALS AND METHODS: We determined the in situ phenotype of mature CD83+ TiDCs using monoclonal antibodies to known activation molecules (CD86 [B7.2], CD80 [B7.1], CD40, CD54, CD1a and HLA-DR). Seventeen primary RCCs, representing four distinct histologies, were evaluated using double-staining immunohistochemical techniques and light microscopy. RESULTS: CD83+ TiDCs were found in all tumors. Expression of CD40 correlated with expression of CD1a on CD83+ TiDCs. Expression of CD54 (ICAM-1) correlated with a lower expression of CD86 (B7.2) as well as a decrease in CD3+ and CD8+ TiLs. CONCLUSIONS: These data suggest a de novo lipid or sugar-based immunogenic antigen presentation by TiDCs. Also, the data support an impaired antigen-presenting capability for CD54+ TiDCs based on the decreased coexpression of CD86 (B7.2) and the decrease of associated CD8+ TiLs.