Baseline Features and Reasons for Nonparticipation in the Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) Study, a Colorectal Cancer Screening Trial.

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy. Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors. Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022. Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals. Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year. Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25). Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Modulable properties of PVA/cellulose fiber composites.

PURPOSE:: Development of PVA/cellulose fiber composite material with modulable properties, obtained through the increase of reinforcement and heat treatments in order to optimize the composite in terms of mechanical, thermal, and degradation properties. METHODS:: The composite was designed selecting as matrix an experimental formulation based on water-soluble, biodegradable, polyvinyl alcohol (PVA) and microcrystalline cellulose (MCC), as reinforcement. Six different formulations, with increasing ratio of MCC content (from 0% to 55% w/w) in PVA, were developed and extruded by a co-rotating twin-screw extruder (TSA FSCM 21/40). Then, samples have been treated through two different thermal conditions (T1, T2) and characterized by scanning electron microscopy, tensile mechanical tests, thermogravimetric analysis, and water degradation tests to investigate, respectively, the influence of MCC ratios and heat treatment on morphological, mechanical, degradation, and thermal properties. RESULTS:: The PVA/MCC composite exhibited a good stress-strain behavior as well as a close correlation between MCC content on tensile, thermal, and degradation properties. The second part of the results includes the analysis of the effects that the thermal treatments (T1, T2) had on the composite. In fact, thermal treatments have allowed improving the thermal and water stability as well as a significant improvement in the considered mechanical parameters due to a possible crosslinking of the PVA matrix. CONCLUSION:: The present work shows how the properties of the PVA/MCC composite can become modular with the aim of extending its range of application as a new sustainable solution in the field of consumer products.

Photocatalytic Activity of Nanotubular TiO2 Films Obtained by Anodic Oxidation: A Comparison in Gas and Liquid Phase.

The availability of immobilized nanostructured photocatalysts is of great importance in the purification of both polluted air and liquids (e.g., industrial wastewaters). Metal-supported titanium dioxide films with nanotubular morphology and good photocatalytic efficiency in both environments can be produced by anodic oxidation, which avoids release of nanoscale materials in the environment. Here we evaluate the effect of different anodizing procedures on the photocatalytic activity of TiO2 nanostructures in gas and liquid phases, in order to identify the most efficient and robust technique for the production of TiO2 layers with different morphologies and high photocatalytic activity in both phases. Rhodamine B and toluene were used as model pollutants in the two media, respectively. It was found that the role of the anodizing electrolyte is particularly crucial, as it provides substantial differences in the oxide specific surface area: nanotubular structures show remarkably different activities, especially in gas phase degradation reactions, and within nanotubular structures, those produced by organic electrolytes lead to better photocatalytic activity in both conditions tested.

Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design.

RATIONALE: Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, risk, and cost, it is important to understand these tests' comparative effectiveness. STUDY DESIGN: The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs. the annual fecal immunochemical test (FIT) in 50,000 average risk individuals. CONFIRM examines whether screening colonoscopy will be superior to a FIT-based screening program in the prevention of CRC mortality measured over 10 years. Eligible individuals 50-75 years of age and due for CRC screening are recruited from 46 Veterans Affairs (VA) medical centers. Participants are randomized to either colonoscopy or annual FIT. Results of colonoscopy are managed as per usual care and study participants are assessed for complications. Participants testing FIT positive are referred for colonoscopy. Participants are surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC. The primary endpoint is CRC mortality. The secondary endpoints are (1) CRC incidence (2) complications of screening colonoscopy, and (3) the association between colonoscopists' characteristics and neoplasia detection, complications and post-colonoscopy CRC. CONFIRM leverages several key characteristics of the VA's integrated healthcare system, including a shared medical record with national databases, electronic CRC screening reminders, and a robust national research infrastructure with experience in conducting large-scale clinical trials. When completed, CONFIRM will be the largest intervention trial conducted within the VA (ClinicalTrials.gov identifier: NCT01239082).

Engineering Thermoplastics for Additive Manufacturing: A Critical Perspective with Experimental Evidence to Support Functional Applications.

BACKGROUND: Among additive manufacturing techniques, the filament-based technique involves what is referred to as fused deposition modeling (FDM). FDM materials are currently limited to a selected number of polymers. The present study focused on investigating the potential of using high-end engineering polymers in FDM. In addition, a critical review of the materials available on the market compared with those studied here was completed. METHODS: Different engineering thermoplastics, ranging from industrial grade polycarbonates to novel polyetheretherketones (PEEKs), were processed by FDM. Prior to this, for innovative filaments based on PEEK, extrusion processing was carried out. Mechanical properties (i.e., tensile and flexural) were investigated for each extruded material. An industrial-type FDM machine (Stratasys Fortus® 400 mc) was used to fully characterize the effect of printing parameters on the mechanical properties of polycarbonate. The obtained properties were compared with samples obtained by injection molding. Finally, FDM samples made of PEEK were also characterized and compared with those obtained by injection molding. RESULTS: The effect of raster to raster air gap and raster angle on tensile and flexural properties of printed PC was evidenced; the potential of PEEK filaments, as novel FDM material, was highlighted in comparison to state of the art materials. CONCLUSIONS: Comparison with injection molded parts allowed to better understand FDM potential for functional applications. The study discussed pros and cons of the different materials. Finally, the development of novel PEEK filaments achieved important results offering a novel solution to the market when high mechanical and thermal properties are required.

Poly-paper: a sustainable material for packaging, based on recycled paper and recyclable with paper.

BACKGROUND: Until now, environmental sustainability issues are almost entirely unsolved for packaging materials. With the final aim of finding materials with a single recycling channel, cellulose fiber/poly(vinyl)alcohol composites were investigated. METHODS: After extrusion and injection molding, samples of composite with different cellulose fiber content (30%, 50% and 70% w/w) were tested. RESULTS: Tensile mechanical tests exhibited an improvement in composite stiffness when the reinforcement content was increased together with a decrease in composite elongation. Solubility tests performed at room temperature and 45°C showed different behavior depending on the water-resistant film applied on the composite (50% cellulose fiber content). In particular, the uncoated composite showed complete solubility after 2 hours, whereas at the same time point, no solubility occurred when a non-water-soluble varnish was used. CONCLUSIONS: The proposed composites, named Poly-paper, appear to warrant further investigation as highly sustainable packaging.

Development of a photocatalytic filter to control indoor air quality.

BACKGROUND: The aim of this work was the development and characterization of a photocatalytic filter for the treatment of indoor air, characterized by a low pressure drop. METHODS: The filter (photocatalytic filter) was based on a polyester substrate additivated with active carbon (Carbotex 150-6), treated with a sol of titanium dioxide (Sol 121-AB; NextMaterials Ltd.) and illuminated with UV LEDs to induce photocatalytic activity. RESULTS: Tests showed that this filter, used in a suitable device for air circulation with a very low noise level, had the ability to block solid particulates, to photocatalytically oxidize a major fraction of volatile organic compounds (VOCs) and deactivate all of the bacteria blocked on the filter, in contrast to traditional commercial air filters on which the bacteria remain viable. CONCLUSIONS: Activated charcoal filters treated with TiO2 and illuminated by UV LEDs were found to be extremely effective in killing bacteria and effective in decreasing VOC and total suspended particulates (TSP).

Improving indoor air quality by using the new generation of corrugated cardboard-based filters.

PURPOSE: Indoor Air Quality (IAQ) is strictly affected by the concentration of total suspended particulate matter (TSP). Air filtration is by far the most feasible suggestion to improve IAQ. Unfortunately, highly effective HEPA filters also have a few major weaknesses that have hindered their widespread use. There is therefore a renewed interest in developing novel, cost-effective filtration systems. We have recently reported the development of cardboard-based filters for bacterial removal that were further implemented and tested herein. METHODS: A parallelepiped filter manufactured by aligning strips of corrugated cardboard and surrounded by a cardboard frame was specifically designed with an internal pocket holding a partially cut antistatic pleated fabric (HP). This filter, together with its parent version (CTRL) and a commercially sourced specimen (CAF), were assessed comparatively in a long-time test to assess their effectiveness on TSP removal. RESULTS: We found that the TSP abatement efficiency (E%) of the HP filter was relatively high and invariable over the 93 days of test and the pressure drop (PD%) decrease because of filter clogging was moderate. Most important, the HP filter was the most effective if assessed in terms of overall yield (Y%) and its performance was quite constant over the entire period considered. CONCLUSIONS: This work disclosed this novel class of corrugated cardboard-based filters as promising tools to ameliorate IAQ in light of their good TSP removal properties that endure over time. Moreover, cardboard is a lightweight, inexpensive, and eco-friendly material and corrugated cardboard-based air filters are very easy to shape and mount on and/or replace in existing ventilation systems.

Development of novel cardboard filters very effective in removing airborne bacteria from confined environments.

PURPOSE: Since bacterial pollution is more troublesome than other nonbiologic air pollutants, the need to control airborne micro-organisms has led to renewed interest in filter media for air filtration in indoor environments. Although mechanical filtration of aerosols by HEPA systems is the most common method for particle removal, these filters characterized by high efficiency usually reveal a higher drop in pressure and noise and are very expensive. On this basis, we aimed to develop novel, very effective air filters for removal of airborne bacteria from confined environments. METHODS: Parallelepiped filters surrounded by a cardboard frame were manufactured by aligning strips of corrugated cardboard and were assessed in terms of airflow rate reduction. Cardboard filters were soaked in isopropanol or used untreated in in vitro experiments for assessment of their antibacterial effect against E. coli and in a testing chamber for assessment of airborne bacterial removal. The surface morphology of cardboard specimens was also investigated by Scanning Electron Microscopy (SEM). RESULTS: Cardboard filters determined a very low decrease in airflow rate. Although specimens showed no antimicrobial behavior, untreated filters showed a maximum of 77% abatement of the airborne bacteria and the alcohol treatment of filters further increased their effectiveness by 14% probably because of their more convoluted surface. CONCLUSIONS: This work disclosed corrugated cardboard-based filters as promising tools for the air treatment of indoor environments because of their excellent microbial abatement properties. Moreover, cardboard is lightweight, inexpensive, and eco-friendly material, and corrugated cardboard-based air filters are very simple in shaping, mounting, and replacing existing ventilation systems.

Anodic oxidation of titanium: from technical aspects to biomedical applications.

Titanium biomaterials are widely employed to produce medical components, such as hip and knee-joint prostheses, bone plates and screws, dental implants, pacemaker cases, surgical equipment, etc. Their diffusion is ascribed to the broad spectrum of optimal mechanical and surface properties, such as the corrosion resistance and correlated low ionic release, the biocompatibility, and especially, the enhanced osseointegration that can be achieved by surface modifications, particularly by suitable anodizing treatments. This review is intended to provide a survey of the wide class of anodic oxidation treatments on titanium, focusing on the oxide structures, morphologies, and compositions that best apply to the variegated fields of titanium applications.

BCL2, BCL6, MYC, MALT 1, and BCL10 rearrangements in nodal diffuse large B-cell lymphomas: a multicenter evaluation of a new set of fluorescent in situ hybridization probes and correlation with clinical outcome.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Although it is a curable disease, fewer than half of patients are cured with conventional chemotherapy. The highly variable outcome reflects a heterogeneous group of tumors, with different genetic abnormalities and responses to therapy. We analyzed 74 cases of diffuse large B-cell lymphoma using interphase fluorescent in situ hybridization with commercially available probes for split-signal targeting BCL-2, BCL-6, MYC, BCL-10, and MALT-1. Gene rearrangements were identified in 48 (65%) of 74 cases. BCL-6 was the most rearranged gene (45%), followed by BCL-2 (21%), BCL-10 (18%), and MYC (16%). No MALT-1 rearrangements were found. When diffuse large B-cell lymphoma cases were subdivided into germinal-center B-cell-like and activated B-cell-like groups, an inverse pattern of BCL-2 and BCL-6 rearrangements was observed. Of interest, the presence of chromosome rearrangements was associated with a worse prognosis. The pattern of cytogenetic abnormalities highlighted the fact not only that diffuse large B-cell lymphoma is a heterogeneous entity but also that even individual cases may contain subclones bearing different chromosomal rearrangements. The relevance and the clinical implication of minor clones showing gene rearrangements are poorly understood; however, this first observation suggests that different rearrangements may be involved in the progression of the disease. The fluorescent in situ hybridization analysis with the panel used in this study is useful to detect the heterogeneity of diffuse large B-cell lymphomas and identify alterations with prognostic implications.

Anodic Spark Deposition treatments to increase reliability of Ti6Al4V modular prostheses.

PURPOSE: The aim of this study was to evaluate whether an Anodic Spark Deposition treatment, which assures increased resistance of titanium alloys to fretting corrosion, improves the structural reliability of Ti6Al4V modular hip prostheses, thus preventing the recently noticed in vivo mechanical failures of these components due to fatigue events. METHODS: Three commercial treatments were tested in this work. Microhardness, roughness and fatigue resistance measurements were carried out to investigate the treatment performances. RESULTS: The experimental tests showed that the implant responded differently based on the treatment. The treatment that assured the best performances induced an increase in fatigue resistance with respect to the initial properties of the non-treated Ti6Al4V alloy. CONCLUSIONS: Since in previous research the same surface treatment was shown to prevent fretting corrosion phenomena, the study tests confirmed that the Anodic Spark Deposition treatment can significantly increase the structural reliability of Ti6Al4V multi-component prostheses.

Mechanical characterization of an innovative dental implant system.

PURPOSE: The research presented is aimed at the characterization of the mechanical resistance of an innovative system of an abutment-fixture connection in dental implants. This innovative connection system is composed of a triangular prismatic connection designed to improve the anti-rotational properties of the implant, and to seal any gap between the abutment and the fixture. METHODS: The mechanical performances of the dental implant system were investigated by means of static mechanical strength tests, which allowed the identification of the bending, torque and compression resistance of the system, and fatigue testing, according to the practice standard - ISO 14801. Surface finishing was also analyzed by scanning electron microscopy (SEM) observations and laser profilometry tests. RESULTS: The analyzed implant exhibited good mechanical characteristics, both in static and in fatigue tests. Moreover, the gap between the fixture and the abutment detected by SEM analyses was restricted, both before and after fatigue tests, being approximately 4 mum in the worst case observed: this is representative of optimal sealing against fluid infiltration. CONCLUSIONS: The modification of traditional dental implants with the introduction of a triangular prismatic connection system not only allowed the implant rotational stability and sealing performances to increase, but also conferred optimal mechanical resistance to the implant.

Retrospective evaluation of clinical outcomes in patients with HER2-positive advanced breast cancer progressing on trastuzumab-based therapy in the pre-lapatinib era.

BACKGROUND: Patients with HER2-positive breast cancer whose disease has become resistant to the anti-HER2 monoclonal antibody trastuzumab can benefit from lapatinib, a dual epidermal growth factor receptor/HER2 tyrosine kinase (TK) inhibitor. Before the availability of this compound, trastuzumab was often continued beyond disease progression, usually in addition to further chemotherapy, an approach which was not based on randomized studies. We sought to retrospectively compare the clinical outcomes of patients who, upon progression during an initial trastuzumab-based regimen, stopped or continued trastuzumab in addition to further chemotherapy. PATIENTS AND METHODS: From the clinical records of 407 patients with HER2-positive advanced breast cancer, we identified 279 patients progressing during an initial trastuzumab-based treatment. Of these patients, 83 continued trastuzumab in addition to chemotherapy, and 112 received chemotherapy alone. RESULTS: We found no difference in response rate (28% vs. 30%; P = .5), median time to second tumor progression (8.4 months vs. 7 months; P = .24), or median postprogression survival (20.6 months and 15.4 months; P = .29) according to whether patients continued or stopped trastuzumab. At multivariate analysis, continuation of trastuzumab was associated with a statistically insignificant trend toward reduced risk of second progression (hazard ratio, 0.753; P = .08). CONCLUSION: Patients with HER2-positive advanced breast cancer developing tumor progression during an initial trastuzumab-based regimen did not seem to benefit significantly from the continuation of trastuzumab in addition to chemotherapy. For these patients, there is evidence from a large randomized trial that effective HER2 targeting can be accomplished by inhibiting the HER2 TK activity with lapatinib.

Topoisomerase IIalpha gene status and prediction of pathological complete remission after anthracycline-based neoadjuvant chemotherapy in endocrine non-responsive Her2/neu-positive breast cancer.

PURPOSE: Topoisomerase IIalpha (Topo II) is a potential marker of responsiveness to anthracycline-based therapy. We analyzed the role of Topo II gene status in the prediction of pathological complete remission (pCR) after primary anthracycline-based chemotherapy in non- endocrine responsive breast cancers overexpressing Her2/neu. METHODS: Twenty-three patients, with T2-T4, ER and PgR absent, overexpressing Her2/neu breast cancers treated with anthracycline-based chemotherapy were evaluated. Topo II gene status was assessed by FISH in pre-treatment tumor specimens and the results were correlated to pathological and clinical responses. RESULTS: Overall, six patients had a pCR (26%). Topo II was amplified in 5 (22%) of the tumors. In all patients with Topo II amplification, Her2/neu gene amplification was also detected. Among patients without amplification, one had polysomia of chromosome (Cr) 17 and four patients had deletion of the Topo II gene. A higher probability of pCR was observed when Topo II amplification and Cr 17 polysomy were present: pCR was reported in 3 of 5 amplified tumors (60%), in the polysomic tumor (amplified plus polysomic 67%) and in only 2 out of 13 tumors without alteration of Topo II status (15%). If we compare the frequency of pCR in tumors with amplification or polysomy versus the frequency of tumors with not amplification (deletion or no modification), a significant difference was detected (p=0.02). One progressive disease (PD) was reported in one tumor with Topo II deletion (1/4, 25%) and one in tumor without any modification of Topo II gene status (1/13, 8%). CONCLUSIONS: In patients with endocrine unresponsive and Her2 overexpressing tumors, Topo II amplification or the presence of chromosome 17 polysomy correlate with a significantly high probability of achieving pCR after neoadjuvant, anthracycline-based chemotherapy. Further prospective studies in order to more clearly define the predictive role of Topo II status in this subgroup of patients are warranted.

Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial.

BACKGROUND: The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. METHODS: The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range <1 to 90 months]). A central assessment of oestrogen receptor (ER), progesterone receptor (PgR) and ERBB2 status using paraffin-embedded primary tumour material was possible for 3650 (74%) patients. ER, PgR, and ERBB2 expression were measured by immunohistochemistry (IHC) and ERBB2-positivity was confirmed by fluorescence in-situ hybridisation (FISH). Positive staining in at least 1% of cells was considered to show presence of ER or PgR expression. Tumours were deemed ERBB2-positive if amplified by FISH, or, for the few tumours with unassessable or unavailable FISH results, if they were IHC 3+. Hazard ratios (HR) estimated by Cox modelling were used to compare letrozole with tamoxifen for DFS, which was the primary endpoint, and to assess treatment-by-covariate interactions. The BIG 1-98 trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00004205. FINDINGS: By central assessment 7% (257 of 3650) of tumours were classified as ERBB2-positive. In 3533 patients with tumours confirmed to express ER, DFS was poorer in patients with ERBB2-positive tumours (n=239) than in those with ERBB2-negative tumours (n=3294; HR 2.09 [95% CI 1.59-2.76]; p<0.0001). There was no statistical evidence of heterogeneity in the treatment effect according to ERBB2 status of the tumour (p=0.60 for interaction), thus, letrozole improves DFS compared with tamoxifen regardless of ERBB2 status. The observed HRs were 0.62 (95% CI 0.37-1.03) for ERBB2-positive tumours and 0.72 (0.59-0.87) for ERBB2-negative tumours. INTERPRETATION: A benefit of letrozole over tamoxifen was noted, irrespective of ERBB2 status of the tumour, and, therefore, ERBB2 status does not seem to be a selection criterion for treatment with letrozole versus tamoxifen in postmenopausal women with endocrine-responsive early breast cancer.

3q26 Amplification and polysomy of chromosome 3 in squamous cell lesions of the lung: a fluorescence in situ hybridization study.

PURPOSE: An overlapping area of gain at 3q26 has been reported in lung squamous cell carcinoma (SCC), but whether this also occurs in preneoplastic/preinvasive squamous cell proliferations and early-stage invasive carcinomas of the lung is still unknown. EXPERIMENTAL DESIGN: We evaluated the prevalence and the clinicopathologic implications of 3q26 amplification and polysomy of chromosome 3 in 31 preneoplastic/preinvasive squamous cell lesions of the bronchial mucosa and in 139 early-stage invasive pulmonary SCC, both of limited growth within the bronchial wall [early hilar SCC (EHSCC)] and involving the pulmonary parenchyma [parenchyma-infiltrating SCC (PISCC)]. Moreover, mRNA expression of two candidate genes (h-TERC and SKI-like), both mapping to the minimal common amplification region, was also studied by quantitative real-time reverse transcription-PCR. RESULTS: 3q26 amplification and polysomy of chromosome 3 were confined to malignant samples, with 37% of invasive SCC, and 27% of severe dysplasias/in situ carcinomas showing these chromosomal abnormalities. Amplification (with minimal common amplification region at 3q26.2), polysomy 3, concurrent amplification and polysomy 3, or other changes (monosomy) were found in 25 SCC and 1 dysplasia, 24 and 2, 2 and 0, and 1 and 0, respectively. Amplification was significantly associated with EHSCC, polysomy 3 with PISCC. 3q26 amplification correlated with increased tumor diameter and a history of smoking, whereas polysomy 3 correlated with tumor diameter, pT class, and p53, p21, and fascin immunoreactivity. No relationship of either 3q26 gain or polysomy was found with patients' survival. Overexpression of h-TERC or SKI-like mRNA was found in 3q26-amplified or polysomic SCC, with higher levels of h-TERC in the former and of SKI-like in the latter. CONCLUSIONS: 3q26 amplification and chromosome 3 polysomy may be related to the development of invasive SCC, with differential distribution in tumor subsets, despite substantial histologic uniformity. Both h-TERC and SKI-like may be involved in tumor progression.

Assessing the status of axillary sentinel lymph nodes of breast carcinoma patients by a real-time quantitative RT-PCR assay for mammaglobin 1 mRNA.

The aim of the study was to assess the accuracy of a real-time quantitative RT-PCR (qRT-PCR) assay for mammaglobin 1 mRNA in the detection of metastatic breast cancer in axillary sentinel lymph nodes (SLN), comparing the results with those of qualitative RT-PCR assays and of an extensive histopathological examination. A retrospective series of 81 SLN from 72 patients and a validation series of 61 SLN from 61 patients were evaluated. In the retrospective series, the qRT-PCR assay was positive for 23 (28.4%) of the 81 SLN. The overall concordance with histopathology was 93.8%, with a sensitivity of 90.9%, a specificity of 94.9%, a positive predictive value (PPV) of 87% and a negative predictive value (NPV) of 96.6%. In the same series, qualitative RT-PCR showed an overall concordance with histopathology of 86.4%, a sensitivity of 72.7%, a specificity of 91.5%, a PPV of 76.2% and a NPV of 90%. In the validation series, including 23 patients with pure in situ carcinoma, the real-time qRT-PCR assay showed an overall concordance with the histopathologic findings of 93.4%, with a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 50.0% and a NPV of 98.2%. We conclude that real-time qRT-PCR assays for mammaglobin 1 are more sensitive and specific that qualitative RT-PCR assays for the detection of metastatic breast carcinoma in axillary SLN, but it should not be regarded as a possible substitute for an extensive histopathological scrutiny of the SLN in the clinical practice.

SP4, a novel anti-cyclin D1 rabbit monoclonal antibody, is a highly sensitive probe for identifying mantle cell lymphomas bearing the t(11;14)(q13;q32) translocation.

Immunohistochemistry is the most widely used approach in the diagnosis of mantle cell lymphoma (MCL). However, its reliability may be hampered by several technical reasons, necessitating the use of alternative techniques such as the identification of the t(11;14)(q13;q32) translocation to characterize such lesions. The authors compared two monoclonal antibodies (DCS-6 and SP4) for assessing cyclin D1 immunoreactivity in a series of 22 MCLs. Their results documented that SP4, a novel rabbit monoclonal antibody, is more effective than the mouse monoclonal antibody DCS-6, one of the most commonly used reagents in daily practice. Although DCS-6 and SP4 were capable of identifying cyclin D1 immunoreactivity in 95.4% and 100% of the cases analyzed, respectively, the prevalence of cyclin D1 immunoreactive neoplastic cells was significantly (P < 0.0001) higher with SP4 (86.6 +/- 13.1%) than with DCS-6 (39.8 +/- 32%). Moreover, the staining intensity was faint in 16 (76.2%) cases and moderate to strong in 5 (23.8%) cases immunostained with DCS- 6, while all the cases showed a moderate to strong immunoreactivity with SP4 (P < 0.0001). According to an arbitrary score based on the percentage of immunoreactive neoplastic cells and staining intensity, only 10 (45.4%) cases were considered high cyclin D1 expressors after staining with DCS-6, whereas all the cases were high expressors with SP4 (P < 0.0001). These data provide evidence that the SP4 monoclonal antibody may be a fast, easy-to-interpret, and reliable surrogate for the detection of the (11;14) translocation by molecular techniques.