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PDF file - 78K, Type of KRAS and EGFR mutations in NSCLC tumors of different histological subtypes.

Non–small cell lung cancer (NSCLC) is a major public health problem, accounting for more cancer-related deaths than any other cancer. Both immunotherapy, based on the expression of tumor-specific antigens, and targeted therapy, based on the presence of oncogenic mutations, are under development for NSCLC. In this study, we analyzed the expression of MAGE-A, a cancer–testis antigen, in tumors from a cohort of patients with resected NSCLC with respect to their clinicopathologic characteristics and their mutational status for the EGFR and KRAS genes. We found MAGE-A expression by IHC in 43% of the tumors. MAGE-A expression was significantly more frequent in squamous tumors than in adenocarcinomas, did not correlate with disease stage, but was correlated significantly with high tumor grade and worse survival. EGFR and KRAS mutations were present in adenocarcinomas, but not in squamous tumors. Whereas the presence of EGFR mutations did not seem to affect survival, the presence of KRAS mutations was associated with early-stage disease and better survival. MAGE-A expression was absent from adenocarcinomas with KRAS mutations, but not significantly different in tumors with or without EGFR mutations. Together, the reported results provide guidance for the design of combination therapies in patients with NSCLC. Cancer Immunol Res; 2(10); 943–8. ©2014 AACR.

PDF file - 570K, Correlation between tumors histological type and grade and disease stage and patients' survival. Analysis of disease-specific survival of patients was assessed using Kaplan-Meier curves and statistical significance of the difference between the groups was determined using the Log-Rank test.

Objective Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. This study assessed the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, versus other biologics in PsA from the Argentinean social security perspective. Methods A semi-Markov model evaluated subcutaneous (sc) treatment with secukinumab 150 mg and 300 mg against other sc treatments such as adalimumab, certolizumab pegol, etanercept, golimumab, ustekinumab, and intravenous treatment infliximab in biologic-naive (with or without moderate to severe psoriasis) and biologic-experienced PsA patients over a lifetime horizon. Response to treatments was determined using the PsA Response Criteria (PsARC) at 12 weeks. Model inputs were derived from randomized controlled trials, network meta-analyses, published literature, and other Argentinean sources. Model outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios. Sensitivity analyses and alternative scenarios with a higher cost option were also conducted. Results Among biologic-naive PsA patients without psoriasis, secukinumab 150 mg provided the highest QALYs (7.18) versus all sc biologics at the lowest cost ($3 755 678 Argentine peso), thus dominating them. Among biologic-naive PsA patients with psoriasis and biologic-experienced PsA patients, secukinumab 300 mg provided highest QALYs (6.99 and 7.53, respectively), dominated infliximab, and was cost-effective versus other sc biologics. Deterministic sensitivity analyses indicated sensitivity of results to variation in PsARC rates, drug acquisition costs, Health Assessment Questionnaire change, and utilities. A probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from an alternative scenario analysis were similar to base-case analysis. Conclusions For both biologic-naive and experienced PsA patients, secukinumab is either a dominant or cost-effective treatment option compared with other biologics in Argentina.

Non–small cell lung cancer (NSCLC) is a major public health problem, accounting for more cancer-related deaths than any other cancer. Both immunotherapy, based on the expression of tumor-specific antigens, and targeted therapy, based on the presence of oncogenic mutations, are under development for NSCLC. In this study, we analyzed the expression of MAGE-A, a cancer–testis antigen, in tumors from a cohort of patients with resected NSCLC with respect to their clinicopathologic characteristics and their mutational status for the EGFR and KRAS genes. We found MAGE-A expression by IHC in 43% of the tumors. MAGE-A expression was significantly more frequent in squamous tumors than in adenocarcinomas, did not correlate with disease stage, but was correlated significantly with high tumor grade and worse survival. EGFR and KRAS mutations were present in adenocarcinomas, but not in squamous tumors. Whereas the presence of EGFR mutations did not seem to affect survival, the presence of KRAS mutations was associated with early-stage disease and better survival. MAGE-A expression was absent from adenocarcinomas with KRAS mutations, but not significantly different in tumors with or without EGFR mutations. Together, the reported results provide guidance for the design of combination therapies in patients with NSCLC. Cancer Immunol Res; 2(10); 943–8. ©2014 AACR.

Immunotherapy with checkpoint inhibitors allowing recovery of effector cell function, has been demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not fully standardized with respect to either quantity or distribution of expression, or regarding the concordance of expression in primary tumor versus metastasis. To assess tumor heterogeneity, we evaluated PD-L1 expression using the Ventana SP-263 assay in paired formalin fixed paraffin embedded (FFPE) blocks from the same primary tumor for each of 22 lung squamous cell carcinoma (SCC), 6 lung adenocarcinoma (ADC), 53 gastric ADC, 55 colorectal ADC, 60 urothelial bladder carcinoma, 3 pancreatic ductal ADC and 4 head and neck SCC. In addition, PD-L1 expression in primary tumor and synchronous metastasis was evaluated in 32 cases of lung neoplasm (10 ADC +22 SCC), 30 cases of gastric adenocarcinoma, 55 cases of colorectal adenocarcinoma, and 16 head and neck SCC, each with corresponding synchronous metastases. PD-L1 expression was determined by pathologist evaluation of the percentage of positive tumor cells and cases were grouped into categories representing Citation Format: Lorenzo Colarossi, Eleonora Aiello, Marie Cumberbatch, Cristina Colarossi, Chris Womack, Lorenzo Memeo. Tumor heterogeneity and primary versus metastatic evaluation of PD-L1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1536.

CD200 is a relatively ubiquitously expressed molecule that plays a role in cancer immune evasion through interaction with its receptors. High expression levels of CD200 have been described in different human malignancies. For example, CD200 has been shown to be targeted after RAS/RAF/MEK/ERK activation in melanoma. Here we present the analysis of CD200 expression in human Multiple Myeloma (MM) samples. We found that CD200-positive cells express ERK and p-ERK. Moreover, UO126, a MEK inhibitor, reduces CD200 expression. Furthermore, we observe that CD200-positive cells show reduced immunogenicity compared to normal lymphocytes and that such immunogenicity increases when UO126 is used. We therefore hypothesize that CD200 expression in MM could suppress antitumor response and that anti-CD200 treatment might be therapeutically beneficial in CD200-expressing tumors.

Luisa Vicari,1,* Cristina La Rosa,2,3,* Stefano Forte,1 Giovanna Calabrese,1 Cristina Colarossi,2 Eleonora Aiello,2 Salvatore Salluzzo,2 Lorenzo Memeo1,2 1IOM Ricerca srl, Viagrande CT, Italy; 2Department of Experimental Oncology, Istituto Oncologico del Mediterraneo, Viagrande CT, Italy; 3Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Roma, Italy *These authors contributed equally to this work Background: Activating transcription factor 5 (ATF5) is a member of the activating transcription/cAMP response element-binding protein family of basic leucine zipper proteins that plays an important role in cell survival, differentiation, proliferation, and apoptosis. The ATF5 gene generates two transcripts: ATF5 isoform 1 and ATF5 isoform 2. A number of studies indicate that ATF5 could be an attractive target for therapeutic intervention in several tumor types; however, so far, the role of ATF5 has not been investigated in papillary thyroid carcinoma (PTC).Methods: Quantitative real-time reverse transcription polymerase chain reaction and immunohistochemical staining were used to study ATF5 mRNA and protein expression in PTC.Results: We report here that ATF5 is expressed more in PTC tissue than in normal thyroid tissue. Furthermore, this is the first study that describes the presence of both ATF5 isoforms in PTC.Conclusion: These findings could provide potential applications in PTC cancer treatment. Keywords: papillary thyroid carcinoma, ATF5, therapeutic target, qRT-PCR, IHC

Diagnostic and prognostic implications of endocrine differentiation were evaluated in 103 common gastric adenocarcinomas and undifferentiated carcinomas. Maturely differentiated exocrine and endocrine phenotypes were evaluated by using gastric exocrine and endocrine markers along with intestinal exocrine and endocrine markers. Immunohistochemical analysis revealed that 66 tumors (64%) were positive for generic endocrine markers such as chromogranin A and/or synaptophysin. The 14 patients with more than 20% tumor cells positive for at least 1 endocrine marker experienced a poorer prognosis than patients with no (n = 37) or 1% to 20% (n = 52) positivity. The 16 carcinomas expressing the maturely differentiated exocrine gastric phenotype significantly correlated with poorer outcome compared with carcinomas with mature exocrine intestinal (n = 22) or mixed/gastrointestinal (n = 64) phenotypes. Among tumors expressing chromogranin A and/or synaptophysin, the maturely differentiated endocrine gastric phenotype (n = 26) was a negative prognostic factor compared with mature endocrine intestinal (n = 21) and mixed/gastrointestinal (n = 5) phenotypes. Endocrine differentiation and maturely exocrine/endocrine gastric phenotypes are associated with an unfavorable prognosis and may identify subsets of patients for tailored therapy.

In order to compare the cost and to find the cost-effectiveness ratio of 0.5 mg/day entecavir versus pegylated interferon in the suppression of the viral replication and the quality of life of chronic hepatitis B patients based on a previously developed economic evaluation by Spackman y Veenstra, we performed, previous data transferability analysis, an adaptation of the model to the Venezuelan reality.To adapt the economic evaluation, we assumed the probabilities of transition between states, in accordance with the effectiveness reported in the original evaluation. The hypothetical cohort was based on the characteristics of patients in recent clinical trials. The model results included the cost of each treatment alternative, entecavir and pegylated interferon, as well as quality adjusted life years (QALYs) gained.Entecavir 0.5 mgprovides 18,25 QALYs compared with 18,12 QALYs provided by pegylated interferon. The cost per QALY was 5.257 BsF for entecavir compared with pegylated interferon whose cost ranges 6.716 y 7.358 BsF per QALY CONCLUSIONS: Entecavir 0.5 mg provides a greater amount of QALYs and a better cost-effectiveness ratio than pegylated interferon showing extended dominancy over this.

Neuroendocrine carcinoma of the urinary bladder is a rare entity, accounting less then 1% of urinary bladder malignancies. The vast majority of the neuroendocrine carcinoma of the urinary bladder is represented by small cell neuroendocrine carcinoma while just few cases of large cell neuroendocrine carcinoma (LCNEC) have been reported. In this cases report we describe a rare case of primary bladder LCNEC. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2474700528951562