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The optimal management for massive rotator cuff tears (MRCTs) without osteoarthritis (OA) remains controversial. The purpose of this study was to evaluate and compare the clinical outcomes of reverse shoulder arthroplasty (RSA) vs. rotator cuff repair (RCR) in patients with MRCTs without OA.We conducted a retrospective data analysis of 68 patients treated for MRCTs via RSA and 215 patients treated for MRCTs via arthroscopic RCR between January 2014 and April 2019. Through propensity score matching, patients were matched for sex, age, tear size, and global fatty degeneration index. Thirty-nine patients in each group were included, and all patients had completed minimal 2-year follow-up. Postoperative radiologic evaluations of healing failure were performed. The visual analog scale score for pain, range of motion, and functional outcome measures including the American Shoulder and Elbow Surgeons score, QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score, Simple Shoulder Test score, and Constant score were assessed and compared between the 2 groups.Healing failure was observed in 10 patients in the RCR group (32.3%). No statistically significant differences in preoperative range of motion and functional scores were found between the RCR and RSA groups. Both groups showed significant pain relief and functional improvement at final follow-up. Patients in the RCR group showed significantly greater forward elevation (156.4° ± 23.8° vs. 139.7° ± 22.4°, P .001) and internal rotation (thoracic vertebra, T8.2 ± 1.2 vs. T9.7 ± 2.6, P = .001). The average American Shoulder and Elbow Surgeons score was 88.3 ± 12.2 in the RCR group and 81.8 ± 16.1 in the RSA group (P = .045). The QuickDASH score was significantly higher in the RCR group (P = .019). A significantly higher Simple Shoulder Test score (9.7 ± 2.8 vs. 8.1 ± 3.0, P = .01) and a significantly higher Constant score (67.2 ± 6.5 vs. 63.2 ± 7.1, P = .011) were seen in the RCR group.Both RSA and RCR are effective and reliable treatment options for MRCTs without OA. However, the RCR group showed better shoulder function improvement than the RSA group. Considering the possible implications of RSA, RCR should be referred to as a first-line treatment option for patients with MRCTs without OA with proper indications.

Bilayered cell sheets were fabricated with coaxial hydro-nanofibrils for three-dimensional (3D) cultivation in a biomimetic environment. Polycaprolactone (PCL) was electrospun and hydrolyzed to release fragmented nanofibrils (NF) in an alkaline condition. Methacrylated gelatin (GelMA) was adsorbed and phototethered on the surface of the fibrils to prepare coaxial NF composed of hydrophilic shells and hydrophobic cores. GelMA layers on the NF were characterized by X-ray photoemission spectroscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The GelMA showed higher decoration level on NF compared to that on native gelatin. GelMA-decorated NF significantly enhanced cell proliferation rate and phenotypic expression of human dermal fibroblasts when spontaneous formation of cell sheets was observed for 7 days. HaCaT cells were layered on top of the fibroblast sheets and further cultivated in air-water interfaces to prepare bilayered skin sheets. After 21 days of incubation, the top layers of the bilayered sheets showed higher expression of pan-keratin, and the dermal cells showed higher proliferation in the GelMA-decorated NF.

BACKGROUND A decreased acromiohumeral distance (AHD) is commonly detected in patients with massive rotator cuff tears (mRCTs). Most studies evaluating fixed humeral elevation have used preoperative or postoperative standardized radiography and not stress radiography. This study aimed to evaluate the predictive role of the preoperative AHD measured using stress radiography (AHD_stress) in rotator cuff healing and function after arthroscopic repair of mRCTs. METHODS The data of 113 patients who underwent arthroscopic repair of mRCTs were analyzed. Postoperative cuff integrity was evaluated using magnetic resonance imaging at 1 year, and shoulder function was evaluated at a mean of 34.9 ± 17.8 months (range, 24-92 months) postoperatively. Forty-seven patients showed healing failure. Propensity score matching (1-1) was performed between the healed group and healing failure group. Thirty-eight patients in each group were matched in the final analysis. The AHD and AHD_stress were defined as the shortest distances from the inferior acromion to the superior humerus on standard anteroposterior radiography and stress radiography (5.4-kg weight applied inferiorly in a neutral position), respectively. The AHD difference (AHD_diff) was defined as the difference between the AHD and AHD_stress values. Receiver operating characteristic curve analysis was performed to determine cutoff values for significant variables. RESULTS No difference in the mean preoperative AHD was found between the healed group (7.5 ± 2.0 mm) and healing failure group (6.9 ± 2.2 mm, P = .234). The AHD_diff value was significantly higher in the healed group (4.4 ± 2.1 mm) than in the healing failure group (3.0 ± 2.0 mm, P = .002; cutoff, 3.2 mm). Patients with an AHD_diff value ≥ 3.2 mm showed a lower healing failure rate (28.9% vs. 71.1%, P < .001) and higher functional scores than patients with an AHD_diff value < 3.2 mm. The AHD_diff value was higher in patients with an American Shoulder and Elbow Surgeons (ASES) score ≥ 80 (4.9 ± 1.9 mm) than in those with an ASES score < 80 (3.1 ± 2.1 mm, P = .024). Among patients with healing failure, only the postoperative AHD showed a significant difference between those with an ASES score ≥ 80 (7.0 ± 2.5 mm) and those with an ASES score < 80 (4.8 ± 2.1 mm, P = .009; cutoff, 4.8 mm). CONCLUSION A reducible AHD, which increased by ≥ 3.2 mm under stress radiography, can be a favorable predictor of rotator cuff healing and function after arthroscopic repair of mRCTs. Our findings suggest that this new and simple radiologic parameter should be considered preoperatively and would be helpful to determine appropriate treatment strategies.

Background:Previous studies have indicated that people with social anxiety disorder (SAD) often experience spontaneous, recurrent images (SRI). It was assumed that Koreans with interdependent self-views may contain more features related to social contexts in their self-images than those reported in Western cultures.Aims:In the present study, we aimed to explore the prevalence and content of SRIs in individuals with SAD in Korea. Furthermore, we investigated the relationship between features of SRIs and variables of SAD.Method:Sixty-four individuals with SAD (27.00 ± 7.42 years, 64.1% female), diagnosed with SAD, completed self-report questionnaires related to social anxiety. Afterwards, a semi-structured interview was used to assess features and content of the individuals’ SRI.Results:Thirty (47%) of the participants reported experiencing SRIs in social situations. The content of the SRIs were classified under three themes: negative self-images, negative images of others, and abstract images. The distress level of SRIs was positively associated with social phobia scales (r = .385, p < .05) and physical anxiety symptoms (r = .478, p < .05). Frequency of SRIs was positively associated with avoidance scores (r = .402, p < .05).Conclusions:The results demonstrated differences in the prevalence and content of the SRIs between Western and non-Western cultures. Fewer individuals with SAD in Korea reported having SRIs, and the content of these SRIs involved people other than the self. Some features of SRIs were associated with variables of SAD.

Invasive mucormycosis is an uncommon but increasing life-threatening fungal infection. The present study investigated clinical characteristics and mortality among patients diagnosed as invasive mucormycosis infection. We retrospectively reviewed a total of 24 histologically proven cases of invasive mucormycosis at two tertiary care referral hospitals between November 2005 and February 2014. Overall survival was 50% (n = 12). The time between onset of symptom and diagnostic procedure proved to be associated with mortality (P = 0.009). In addition, preexisting renal failure and thrombocytopenia demonstrated trends toward a poor outcome in our study (P = 0.089 and 0.065, respectively). On multivariate regression analysis, delayed diagnostic procedure (more than 16 days after the onset of symptoms) was an independent predictor of mortality (OR= 12.34, 95% CI, 1.43-10.64; P = 0.022). Mucormycosis is a destructive fungal infection that is associated with high mortality rates, ranging from 40% to 100% depending on the form of disease. When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease.

Background/Aims As the incidence rate of and mortality from pseudomembranous colitis (PMC) are increasing worldwide, it is important to study the simple predictive risk factors for PMC among patients with hospital-acquired diarrhea (HAD). This study focused on identifying the clinical risk factors that can easily predict PMC. Methods The presumed HAD patients were prospectively recruited at the Hallym University Kangdong Sacred Heart Hospital. Results Age of 70 and older (adjusted odds ratio [OR], 1.76; 95% confidence interval [CI], 1.12 to 0.75), use of proton pump inhibitors (adjusted OR, 4.07; 95% CI, 2.512 to 6.57), use of cephalosporins (adjusted OR, 2.99; 95% CI, 1.82 to 4.94), and underlying cancer (adjusted OR, 1.72; 95% CI, 1.04 to 2.82) were independent risk factors for PMC in the multivariate logistic regression analysis. The prevalence of PMC was very low in the patients with HAD who exhibited no risk factors. Conclusions The risk factors for PMC in patients with HAD included cephalosporin use, proton pump inhibitor use, old age, and cancer. Considering the strongly negative predictive values of these risk factors, endoscopic evaluation can be delayed in patients with HAD without risk of developing PMC.

Chromosomal microarray technology represents the technical convergence of molecular genetics and cytogenetics, and is rapidly revolutionizing modern cytogenetics. Expected genomic aberrations are accurately identified and provide readily interpretable results that are suitable for clinical risk stratification and therapeutic strategies. The application of array technology in prenatal genetic diagnosis provides distinct advantages over conventional cytogenetic analysis in detecting both the majority of microscopic and submicroscopic chromosomal abnormalities. In the last few years, the validity of array technology has become obvious to medical and laboratory communities involved in prenatal diagnostic testing. However, whether or not microarray analysis is sufficient for the detection of cytogenetic abnormalities in prenatal diagnosis and if traditional cytogenetics continue to be important in this new era has yet to be confirmed. In the present study, we systematically reviewed the current status of microarray technology in the identification of pathogenic genomic imbalances and discussed practical considerations for its routine implementation in prenatal diagnosis.

Conventional urine cytology has a poor prognostic performance for detecting bladder cancer, particularly for low-grade tumors. Fluorescence in situ hybridization (FISH) for chromosomes altered in bladder cancer and testing for antigens selectively expressed in tumors are promising alternatives. This study investigated the use of FISH for detecting aneuploidy of chromosomes 3, 7, 17, and 9p21 and reverse transcriptase PCR (RT-PCR) for the expression of melanoma associated antigen (MAGE) genes for the diagnosis of bladder cancer in voided urine specimens. The two techniques were compared with cystoscopic bladder biopsy results in 47 patients with urothelial cancer and 15 patients with benign prostatic hyperplasia. FISH detected cancer in 42 of 47 patients (89.4%). This was significantly higher than the detection rate 30 of 47 patients (64.3%) by MAGE RT-PCR (P < 0.001). The sensitivity of FISH increased with histologic grade and stage of the tumors, correctly identifying 77.8% of pTa and pTis, 94.1% of pT1, and 100% of Pt2-4 tumors. MAGE, however, showed a decreased sensitivity in high grade advanced tumors; it was positive in 66.7% of pTa and pTis, 70.6% of pT1, and 50% of Pt2-4 tumors. Together, the tests correctly identified urothelial cancer in 46 of 47 patients (97.9%). Combined FISH and MAGE RT-PCR testing may offer a promising alternative to conventional urine cytology in screening high-risk populations and in monitoring bladder cancer patients for recurrent tumor.

Purpose Tenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF. Materials and methods We prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naive patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C. Results The eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m²) to 144 wks (89.0±14.7 mL/min/1.73 m²) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naive group at 144 wks (89.7 mL/min/1.73 m² vs. 98.4 mL/min/1.73 m², p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m² in eGFR (MDRD) at 144 wks. Conclusion These data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF.

PURPOSE Pentraxin 3 (PTX3) has been suggested to be a prognostic marker of mortality in severe sepsis. Currently, there are limited data on biomarkers including PTX3 that can be used to predict mortality in severe sepsis patients who have undergone successful initial resuscitation through early goal-directed therapy (EGDT). MATERIALS AND METHODS A prospective cohort study was conducted among 83 severe sepsis patients with fulfillment of all EGDT components and the achievement of final goal. Plasma PTX3 levels were measured by sandwich ELISA on hospital day (HD) 0, 3, and 7. The data for procalcitonin, C-reactive protein and delta neutrophil index were collected by electric medical record. The primary outcome was 28-day all-cause mortality. RESULTS 28-day all-cause mortality was 19.3% and the median (interquartile range) APHCH II score of total patients was 16 (13-19). The non-survivors (n=16) had significantly higher PTX3 level at HD 0 [201.4 (56.9-268.6) ng/mL vs. 36.5 (13.7-145.3) ng/mL, p=0.008]. PTX3 had largest AUC(ROC) value for the prediction of mortality among PTX3, procalcitonin, delta neutrophil index, CRP and APACHE II/SOFA sore at HD 0 [0.819, 95% confidence interval (CI) 0.677-0.961, p=0.008]. The most valid cut-off level of PTX3 at HD 0 was 140.28 ng/mL (sensitivity 66.7%, specificity 73.8%). The PTX3 and procalcitonin at HD 0 showed strong correlation (r=0.675, p

Chromosomal alterations are a predominant genomic force contributing to the development of lung adenocarcinoma (ADC). High density genomic arrays were conducted to identify critical genetic landmarks that may be important mediators in the formation or progression of early‑stage ADC. In this study, the most noteworthy and consistent observation was a copy number gain on the short arm of chromosome 7, which was detected in 85.7% (12/14) of cases. Notably, three distinct regions of amplification were identified between the 7p22.3 and q11.2 regions in 28.6% (4/14) of cases; at a size of 4.1 Mbp (7p22.3‑p21.1), 2.6 Mbp (7p15.2-p14.1) and 1.5 Mbp (7p12.3‑p11.2). Variations of the 7p11.2 locus that encodes EGFR are known to be oncogenic. Furthermore, potential target genes were identified that were previously not assumed to be involved in the pathogenesis of ADC, including CALM1P2 (7p11.2), HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA13 (7p15.2) and LOC442586, LOC442589, LOC442282, FAM20C and LOC442651 (7p22.3). The present study determined critical regions on the 7p arm of chromosome 7, which were implicated in ADC. The pattern of rearrangements on the 7p arm may be a consequence of the high density of potential targets and the identified genes at the 7p regions may aid in the development of therapeutic targets for ADC.

Microarray-based cytogenetics is revealing the tremendous fluidity and complexity of the human genome, and is starting to illustrate the implications of genomic variability with respect to human health and disease. In the last few years, the robustness of array-based technologies has provided accurate diagnosis and appropriate clinical management in a timely and efficient manner for identifying genomic defects of congenital and developmental abnormalities including developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASD) and/or multiple congenital anomalies (MCA). The implementation of this technology in these categories of disorders has been thoroughly evaluated and is now recommended as a first-line diagnostic approach for clinically suspected genetic disorders. However, clinical application of array-CGH in postnatal evaluation raises the debate of whether array-CGH will replace traditional cytogenetics in the near future and whether there is still a role for karyotyping and FISH. In this article, we therefore review the current status of array-based technology use for postnatal diagnosis and predict that it will replace standard cytogenetics as a first-line test for clinical evaluation in these population groups.

The lymph node metastatic (LNM) spread of tumor cells is a frequent event in the initial process of cancer dissemination and is a powerful independent prognostic indicator in gastric adenocarcinoma (GAC). High density genomic arrays were conducted to identify molecular markers associated with lymph node metastasis in GAC. In the genome-wide profile, large copy number gains involving chromosomes 1p, 3q, 8q, 9q, 11q, 16p, 19p, and 20q (log2 ratio >0.25) (>40% of patients) were more prevalent than copy number losses. The most notable finding was copy number gains at the long arm of chromosome 11, which occurred in 75.0% of lymphatic metastasis GAC cases, and the delineated minimal common region was 11q24.2-q12.1. More specifically, 2 amplified (>1 log2 ratio) loci on the 11q13.3 region were detected in 12.5% of the cases. The first locus, covers a region of ~7.7 Mbp, and comprises the representative oncogene of cyclin D1 (CCNDI). This finding occurred in 12.5% of the cases. Additionally, an oral cancer overexpressed 1 (ORAOV1) gene was identified as a probable target within the 11q13 amplicon, which previously was not assumed to play a pathogenic role in GACs (12.5%). A second locus spanning 7.8 Mbp on 11q13.3 without associated genes also showed high-level amplifications in 12.5% of the GACs. This study indicates that the long arm of chromosome 11 harbors protooncogenes that are associated with lymphatic metastasis formation and the ORAOV1 gene at the 11q13.3 region could be a potential target and serve as an indicator for the presence of occult metastases in GAC.

Microsatellite instability (MSI) is a hyper-mutable phenotype caused by the loss of DNA mismatch repair activity, and plays a crucial role in gastric carcinogenesis. To clarify the role of genetic instability in relation to clinicopathological variables, and to identify predictive MSI markers that facilitate the early detection and improve the classification of gastric carcinomas (GCs), 13 microsatellite (MS) loci, including the National Cancer Institute (NCI) panel of MS markers (D2S123, D5S346, D17S250, BAT25 and BAT26) and 8 dinucleotide repeats (D3S1260, D5S107, D5S409, D17S261, D17S520, D17S855, D18S34 and D18S61) were studied in GC patients. MSI was found in 88.2% (30/34) of GC cases and the number of high-frequency MSI (MSI-H, 23.5%, 8/34), low-frequency MSI (64.7%, 22/34), and stable MSI (11.8%, 4/34), was calculated. Among the MS loci analyzed, D18S34 and D17S261 (15/34, 44.1%) exhibited the highest frequency of MSI, followed by D2S123 (14/34, 41.2%), D5S107, D5S346, D5S409 and D18S61 (12/34, 35.3%) (MSI>35%). MSI-H was particularly prevalent in older patients and was mainly found in the antrum and poorly differentiated tumors. Furthermore, MSI-H was significantly associated with lymph node involvement cases in females. One notable finding in this analysis was that the markers, D17S250 and D17S520, exhibited a significantly higher percentage of MSI in advanced gastric carcinomas than in early gastric carcinomas (P=0.046 and 0.046, respectively), and the D17S520 and BAT26 loci represented significant different correlations between the tumor stages (P=0.038 and 0.042, respectively). This study indicates that the novel markers, D18S34 and D17S261, perform more favorably than the NCI panel for the detection of MSI, and the D17S520 locus presents a potential target for predicting the clinical impact of GC. These novel MS loci may prove to be beneficial and independent tools for the construction of a comprehensive genetic classification for GC cases.

PCDH10has been implicated as a tumor suppressor, since epigenetic alterations of this gene have been noted in multiple tumor types. However, to date, studies regarding its role in acute and chronic leukemias are lacking. Here, we have investigated the presence of promoter hypermethylation of two CpG islands of thePCDH10gene by methylation-specific PCR in 215 cases of various subsets of myeloid- and lymphoid-lineage leukemias. We found thatPCDH10promoter hypermethylation was frequent in both B-cell (81.9%) and T-cell (80%) acute lymphoblastic leukemia (ALL), while it was present in low frequency in most subtypes of myeloid leukemias (25.9%) and rare in chronic myeloid leukemia (2.2%).PCDH10expression was downregulated via promoter hypermethylation in primary ALL samples (N!4) and leukemia cell lines (N!11). The transcriptional repression caused byPCDH10methylation could be restored by pharmacologic inhibition of DNA methyltransferases. ALL cell lines harboring methylation-mediated inactivation ofPCDH10were less sensitive to commonly used leukemia-specific drugs suggesting thatPCDH10methylation might serve as a biomarker of chemotherapy response. Our results demonstrate thatPCDH10is a target of epigenetic silencing in ALL, a phenomenon that may impact lymphoid-lineage leukemogenesis, serve as an indicator of drug resistance and may also have potential implications for targeted epigenetic therapy. V C 2011 Wiley Periodicals, Inc.

Chromosomal alterations are a major genomic force contributing to the development of lung cancer. We subjected 22 cases of squamous cell carcinoma of the lung (SCC) to whole-genome microarray-CGH (resolution, 1 Mb) to identify critical genetic landmarks that might be important mediators in the formation or progression of SCC. On a genome-wide profile, copy number losses (log 2 ratio

Homozygous deletions (HDs) are major genomic forces contributing to the development of many solid tumors. To identify critical tumor-suppressor loci involved in the pathogenesis of gastric carcinoma (GC), a high-resolution microarray-CGH was performed in a series of 27 GC patients. On a genome-wide profile, five distinct HD (log 2 ratio

Background The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown. Methods High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). Results On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs. Conclusion Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of the squamous cell carcinoma of the lung.

Identification of molecular alterations in biological fluids has been proposed as a powerful tool for cancer diagnosis. The purpose of this study was to identify cells that carry chromosomal alterations indicative of malignancy-specifically, gains in the loci 5p15.2 (D5S23, D5S721), 6p11 approximately q11, 7p12 (EGFR), and 8q24.12 approximately q24.13 (MYC)-for the detection of lung cancer using induced sputum. The overall sensitivity of the multicolor fluorescence in situ hybridization (FISH) assay from 52 lung cancer patients was 71% and the specificity was 100% (15 of 15). The most frequently detected gains were at 7p12 (EGFR) in 17 of 24 completely resectable early-stage (II+IIIA) non-small cell lung cancers (NSCLC) (71%). There was a statistically significant increase in the proportion of cases with gains of EGFR in squamous cell carcinomas (SCC), compared with adenocarcinomas (AC) (82 vs. 43%, respectively; P = 0.017), and a higher average EGFR gene copy number in the SCCs than in the ACs (5.04 vs. 3.78, respectively; P = 0.013) in 41 NSCLCs. Conversely, a gain at the 6p11 approximately q11 and 8q24.12 approximately q24.13 (MYC) regions appears to have a higher frequency of gain in the ACs (71 and 86%, respectively) than in the SCCs (48 and 56%, respectively). The results of this study showed the potential utility of the LAVysion FISH assay for the detection of lung cancer by a noninvasive technique based on the analysis of genetic alterations of induced sputum. Defining abnormalities in sputum specimens as FISH aneusomy may be a possible diagnostic method for the early detection of lung cancer in screening of high-risk populations and monitoring for recurrence.

Detection of genetic alterations could provide a tool as an adjuvant for the diagnosis of non-small cell lung cancer (NSCLC) and to define patients at risk for early relapse. In this study, a multi-target fluorescence in situ hybridization (FISH) assay was conducted to investigate the correlation between the alterations of chromosomes, including 5p15.2, 6p11.1-q11, 7p12, and 8q24.12-q24.13 (LaVysion Test), and clinicopathological variables, and to clarify the potential of the multi-target FISH assay in 37 NSCLC. The most notable finding was the higher frequency of a gain in chromosome 5p15.2 in early-stage (I+IIa) lung cancers. The frequency of the gain was 81.3% (16/22) in stage I tumors. The frequencies of gains in 6p11.1-q11 and 8q24.12-q24.13 were 61.5% (8/13) and 84.6% (11/13) in stage IIIa cancers, as compared with lower frequencies in stage I tumors at 25.0% and 31.3%, respectively. There was also a significant difference in the histological type. Our results suggest that a gain in 6p11.1-q11 and 8q24.12-q24.13 plays an important role in tumor progression and is associated with histological differentiation. On the other hand, gene amplification in the 5p region was one of the most consistent alterations in early-stage lung cancer, and thus a series of genes in the critical 5p15.2 region might potentially associated with the development of lung cancer.

Genetic alterations have been recognized as an important event in the carcinogenesis of gastric cancer (GC). We conducted high resolution bacterial artificial chromosome array-comparative genomic hybridization, to elucidate in more detail the genomic alterations, and to establish a pattern of DNA copy number changes with distinct clinical variables in GC. Our results showed some correlations between novel amplified or deleted regions and clinical status. Copy-number gains were frequently detected at 1p, 5p, 7q, 8q, 11p, 16p, 20p and 20q, and losses at 1p, 2q, 4q, 5q, 7q, 9p, 14q, and 18q. Losses at 4q23, 9p23, 14q31.1, or 18q21.1 as well as a gain at 20q12 were correlated with tumor-node-metastasis tumor stage. Losses at 9p23 or 14q31.1 were associated with lymph node status. Metastasis was determined to be related to losses at 4q23 or 4q28.2, as well as losses at 4q15.2, 4q21.21, 4q 28.2, or 14q31.1, with differentiation. One of the notable aspects of this study was that the losses at 4q or 14q could be employed in the evaluation of the metastatic status of GC. Our results should provide a potential resource for the molecular cytogenetic events in GC, and should also provide clues in the hunt for genes associated with GC.