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      • Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior

        Panagiotou, Ioannis,Georgiannos, Stavros N.,Tsiambas, Evangelos,Karameris, Andreas,Konstantinou, Marios,Lazaris, Andreas C.,Kavantzas, Nikolaos,Vilaras, George,Patsouris, Efstratios Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

        Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

      • KCI등재

        Intrapulmonary Solitary Fibrous Tumor Masquerade Sigmoid Adenocarcinoma Metastasis

        Timothy Sakellaridis,Ioannis Koukis,Theodora Marouflidou,Ioannis Panagiotou,Anastasios Piyis,Konstantinos Tsolakis 대한흉부외과학회 2013 Journal of Chest Surgery (J Chest Surg) Vol.46 No.4

        Solitary fibrous tumor is a rare spindle cell mesenchymal tumor entity, with either benign or malignant behavior that cannot be accurately predicted by histological findings. An intrapulmonary site of origin is even rarer. We report a case of a 51-year-old woman in whom an abnormal nodule in the lower right lung was detected during staging for sigmoid adenocarcinoma. The nodule was excised and pathological examination revealed an intrapulmonary solitary fibrous tumor.

      • SCISCIESCOPUS

        Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

        Sampson, Joshua N.,Wheeler, William A.,Yeager, Meredith,Panagiotou, Orestis,Wang, Zhaoming,Berndt, Sonja I.,Lan, Qing,Abnet, Christian C.,Amundadottir, Laufey T.,Figueroa, Jonine D.,Landi, Maria Teres U.S. Dept. of Health, Education, and Welfare, Publ 2015 Journal of the National Cancer Institute Vol.107 No.12

        <P>Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.</P>

      • KCI등재

        Degenerative Cervical Myelopathy: A 7-Letter Coding System That Supports Decision-Making for the Surgical Approach

        Luca Papavero,Gregor Schmeiser,Ralph Kothe,Bronek Boszczyk,Oliver Heese,Yoshiharu Kawaguchi,Anna MacDowall,Claes Olerud,Nikolaos Paidakakos,Anastasios Panagiotou,Tobias Pitzen,Marcus Richter,K. Daniel 대한척추신경외과학회 2020 Neurospine Vol.17 No.1

        Objective: To validate with a prospective study a decision-supporting coding system for the surgical approach for multilevel degenerative cervical myelopathy. Methods: Ten cases were presented on an internet platform, including clinical and imaging data. A single-approach (G1), a choice between 2 (G2), or 3 approaches (G3) were options. Senior and junior spine surgeons analyzed 7 parameters: location and extension of the compression of the spinal cord, C-spine alignment and instability, general morbidity and bone diseases, and K-line and multilevel corpectomy. For each parameter, an anterior, posterior, or combined approach was suggested. The most frequent letter or the last letter (if C) of the resulting 7-letter code (7LC) suggested the surgical approach. Each surgeon performed 2 reads per case within 8 weeks. Results: G1: Interrater reliability between junior surgeons improved from the first read (κ=0.40) to the second (κ=0.76, p<0.001) but did not change between senior surgeons (κ=0.85). The intrarater reliability was similar for junior (κ=0.78) and senior (κ=0.71) surgeons. G2: Junior/senior surgeons agreed completely (58%/62%), partially (24%/23%), or did not agree (18%/15%) with the 7LC choice. G3: junior/senior surgeons agreed completely (50%/50%) or partially (50%/50%) with the 7LC choice. Conclusion: The 7LC showed good overall reliability. Junior surgeons went through a learning curve and converged to senior surgeons in the second read. The 7LC helps less experienced surgeons to analyze, in a structured manner, the relevant clinical and imaging parameters influencing the choice of the surgical approach, rather than simply pointing out the only correct one.

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