Effects of Eribulin on the RNA Content of Extracellular Vesicles Released by Metastatic Breast Cancer Cells.

Extracellular vesicles (EVs) are small lipid particles secreted by almost all human cells into the extracellular space. They perform the essential function of cell-to-cell communication, and their role in promoting breast cancer progression has been well demonstrated. It is known that EVs released by triple-negative and highly aggressive MDA-MB-231 breast cancer cells treated with paclitaxel, a microtubule-targeting agent (MTA), promoted chemoresistance in EV-recipient cells. Here, we studied the RNA content of EVs produced by the same MDA-MB-231 breast cancer cells treated with another MTA, eribulin mesylate. In particular, we analyzed the expression of different RNA species, including mRNAs, lncRNAs, miRNAs, snoRNAs, piRNAs and tRNA fragments by RNA-seq. Then, we performed differential expression analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and miRNA-target identification. Our findings demonstrate the possible involvement of EVs from eribulin-treated cells in the spread of chemoresistance, prompting the design of strategies that selectively target tumor EVs.

Hyponatremia is a Predictor of Clinical Outcome for Resected Biliary Tract Cancers: A Retrospective Single-Center Study.

INTRODUCTION: Biliary tract cancers (BTC) include both gallbladder cancer and cholangiocarcinoma, both of which have a poor prognosis. The aim of our study was to evaluate the main clinical prognostic factors in this setting and to assess their impact on overall survival (OS). METHODS: We retrospectively analyzed data collected on 64 patients with BTC who underwent surgery with radical intent at our institution. OS was estimated using the Kaplan-Meier method. The Cox regression model was used to perform univariate and multivariate analyses. RESULTS: Preoperative hyponatremia was found to be an independent prognostic factor that correlated negatively with prognosis, with hyponatremic patients having a poor OS compared to the group of patients with normal serum sodium levels (9.44 vs. 15.47 months; p = 0.0215). In addition, high preoperative values for carbohydrate antigen 19-9 (Ca19.9), a tumor marker for some gastrointestinal cancers, and lactate dehydrogenase (LDH) were found to be prognostic factors for a significant reduction in OS (Ca19-9: 7.14 vs. 24.22 months, p = 0.0088; LDH: 1.70 vs. 15.47 months, p = 0.0384). CONCLUSION: Identification of these prognostic factors may support strategies to identify, in clinical practice, those subgroups of patients with a favorable or unfavorable prognosis before surgical treatment and, therefore, to guide therapeutic choices. In particular, to our knowledge, this is the first report of the prognostic role of serum sodium level in BTC. Early detection and careful monitoring of hyponatremia and supportive therapy can help to improve the treatment and prognosis of BTC.

Prognostic relevance of programmed cell death protein 1/programmed death-ligand 1 pathway in thymic malignancies with combined immunohistochemical and biomolecular approach.

BACKGROUND: The aim of the study was to investigate Programmed cell Death protein 1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) and their mRNA expression in thymic epithelial tumors (TETs). RESEARCH DESIGN AND METHODS: We analyzed 68 samples of formalin-fixed paraffin-embedded tissue (63 thymomas and 5 thymic carcinomas). PD-1 and PD-L1 protein expression were evaluated by immunohistochemistry, and mRNA expression was evaluated by real-time PCR. RESULTS: M/F ratio was 33/35, and median age was 60.5 years. Twenty patients had Myasthenia Gravis (MG). In the subgroup with large tumors (>5 cm), PD-L1 mRNA overexpression was significantly associated with worse prognosis vs. patients with no mRNA overexpression (p = 0.0083) and simultaneous PD-L1 immunostaining (>1%); PD-L1 mRNA overexpression was significantly associated with worse prognosis, respect to patient with PD-L1 negative immunostaining, and no PD-L1 mRNA overexpression (p = 0.0178). The elderly patients (>60 years) with large tumors showed worse prognosis (p = 0.0395). PD-L1 immunostaining (>50%) resulted to be significantly associated with MG. CONCLUSIONS: Our data suggest the potential involvement of the PD-1 and PD-L1 pathway in TETs' progression. According to our results, it may be helpful to design future trials with anti-PD-1 drugs to establish high-risk patients after surgery.

The role of angiogenetic single-nucleotide polymorphisms in thymic malignancies and thymic benign lesions.

BACKGROUND: We previously showed that selected single-nucleotide-polymorphisms (SNPs) of genes involved in angiogenesis influence the aggressiveness of thymic epithelial tumors (TETs). This study analyzes their role in TETs and in thymic benign lesions, in order to investigate potential correlation with risk and outcome. METHODS: Genomic DNA was extracted from paraffin-embedded tissue of 92 patients, undergoing surgery at our Institution. We investigated by Real-Time PCR the SNPs of the following genes: platelet-derived growth factor receptor-α (PDGFRα), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor-2 and 3 (VEGF-2, VEGFR-3), excision repair cross-complementation group-1 (ERCC1). RESULTS: Fifty-seven TETs and 35 thymic benign lesions were included into the study. Frequency of SNPs was as follows: rs2057482 C, rs11158358 C and rs11549465 C polymorphisms of HIF1-a: thymomas < general population (P=0.008, P=0.007, and P=0.044 respectively). HIF1-a alleles: general population > study groups, rs1951795C SNP (P=0.026 for benign lesions and P=0.0007 for thymomas), rs10873142T SNP (P=0.008 and P=0.001 respectively), rs12434438 A SNP (P=0.034 and P=0.0007) and rs2301113A SNP (P=0.027 and P=0.010). rs699947C polymorphism of VEGF-A: benign lesions > general population (P=0.012). CONCLUSIONS: This is the first study investigating the angiogenetic polymorphisms in thymic benign lesions and TETs. SNPs analysis may represent a further asset in identification of patients who could benefit from anti-angiogenetic therapy.

Pre-treatment systemic immune-inflammation represents a prognostic factor in patients with advanced non-small cell lung cancer.

BACKGROUND: Inflammation plays an important role in pathogenesis, development and progression of lung cancer. The aim of the study is to assess the prognostic role of Systemic Immune-Inflammation Index (SII), obtained by analyzing the neutrophil, lymphocyte and platelet counts, and to design prognostic models for patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). METHODS: We conducted an analysis on 311 patients with advanced NSCLC, treated with first line chemo- or targeted therapy till June 2015 at our Institution. Patients were stratified in two groups with SII ≥1,270 (Group A) vs. SII <1,270 (Group B). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The best SII cutoff was identified by X-tiles program. A Cox regression model was carried out for univariate and multivariate analyses. RESULTS: At baseline, 179 patients had SII ≥1,270 (Group A), whilst 132 had lower SII (Group B). The median OS was 12.4 months in Group A and 21.7 months in Group B (P<0.001), whilst the median PFS was 3.3 and 5.2 months, respectively (P=0.029). At multivariate analysis, male gender, ECOG-PS ≥2 and SII >1,270 were predictors of worst OS, whilst IV tumor stage was only slightly significant (P=0.08). Otherwise, only wild-type EGFR status and SII ≥1,270 were independent prognostic factors for worst PFS. CONCLUSIONS: Pre-treatment SII is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies.

Syndrome of inappropriate anti-diuretic hormone secretion in cancer patients: results of the first multicenter Italian study.

BACKGROUND: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting. METHODS: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015. Data on clinical-pathological characteristics, anticancer therapies, hyponatremia, and related treatments were statistically analyzed. RESULTS: The majority were lung cancer patients (73%) with metastatic disease at the onset of hyponatremia (83%). A total of 76 patients (84%) were hospitalized because of SIADH and less than half (41%) received tolvaptan for SIADH treatment. The duration of hospitalization was significantly longer in patients who did not receive tolvaptan and in those who do not reach sodium normalization during hospitalization. Patients who experienced a second episode of hyponatremia following tolvaptan dose modification/discontinuation presented a significantly lower serum sodium value at the time of hospitalization and minimum sodium value during hospitalization compared with patients who had not experienced another episode. The severity of hyponatremia, defined as minimum sodium value during hospitalization with a cut-off value of 110 mmol/l, and not obtaining sodium correction during hospitalization significantly correlated with overall survival rate. CONCLUSIONS: Hyponatremia due to SIADH could result in longer hospitalization and in a decreased overall survival when not adequately treated, and tolvaptan represents an effective treatment with a potential effect of both improving overall survival and decreasing duration of hospitalization.

Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy.

The aim of the study was to assess, for the first time, the prognostic role of hyponatremia and sodium normalization in patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer.Four hundred thirty-three patients with advanced non small cell lung cancer were treated with first line chemo- or targeted therapy between 2006 and 2015 at our institutions. Patients were stratified in two groups, with or without hyponatremia (group A and B, respectively). Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. A Cox regression model was carried out for univariate and multivariate analyses.Sixty-nine patients (16%) presented with hyponatremia at the start of first-line therapy. The median OS was 8.78 months in Group A and 15.5 months in Group B (p < 0.001), while the median PFS was 4.1 months and 6.3 months respectively (p = 0.24). In Group A, median OS was significantly higher in patients who normalized their sodium levels (11.6 vs. 4.7 months, p = 0.0435). Similarly, the median PFS was significantly higher in patients who normalized their sodium levels (6.7 vs. 3.3 months, p = 0.011). At multivariate analysis, sodium normalization was an independent prognostic factor for both OS and PFS.Sodium normalization during first-line therapy is an independent prognostic factor for OS and PFS in patients with advanced lung cancer treated with first-line therapies. Frequent clinical monitoring and prompt treatment of hyponatremia should be emphasized to optimize the outcome of these patients.

Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex.

BACKGROUND: Lung cancer seems to have different epidemiological, biomolecular and clinical characteristics in females than in males, with a better prognosis for women. The aim of the study is to determine gender differences in lung adenocarcinoma in terms of androgen (AR), estrogen (ER)α and progesterone (PgR) receptors expression and their impact on outcome. RESULTS: Overall survival was significantly better in ERα and in PgR positive lung adenocarcinoma patients (median survival 45 vs. 19 months).Eight out of 62 patients showed positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively). There was a significant difference in survival between patients with vs. without c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median survival was greater in positive expression of c-AR than for women with negative c-AR (45 vs. 21 months). MATERIALS AND METHODS: We conducted an analysis on a cohort of 62 patients with advanced NSCLC treated at our institution. We investigated the immunohistochemical expression of n/c AR, ERα and PgR in 62 NSCLC and we correlated it with patients' clinic-pathologic characteristics and with prognosis. CONCLUSIONS: Our results showed that the positive expression of one hormonal receptor could represent a prognostic factor.Furthermore our study suggests that AR should become object of close examination in a larger series of lung adenocarcinoma patients, also for selection of the patients with best prognosis that can perform more chemotherapy lines.

Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in cancer patients treated with these agents. MATERIALS AND METHODS: The scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. RESULTS: 4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12). CONCLUSION: Treatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents.

Hyponatremia in cancer patients: Time for a new approach.

Hyponatremia is a common electrolyte disorder in cancer patients. It may be related to cancer, to anti-cancer therapy or to other concomitant treatments. In this setting hyponatremia is often caused by the syndrome of inappropriate anti-diuretic hormone secretion, which is due to the ectopic production of antidiuretic hormone (vasopressin), to extracellular fluid depletion, to renal toxicity caused by chemotherapy or to other underlying conditions. Recent studies suggested that hyponatremia might be considered a negative prognostic factor for cancer patients therefore its early detection, monitoring and management might improve the patient's outcome. Treatment of hyponatremia depends on patient's symptoms severity, onset timing and extracellular volume status. In this review we summarize the main causes of hyponatremia in cancer patients and its management, including the available treatment options.

Medical treatment for gastro-entero-pancreatic neuroendocrine tumours.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -ß), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.

Prognostic models to predict survival in patients with advanced non-small cell lung cancer treated with first-line chemo- or targeted therapy.

BACKGROUND: We aimed to assess the prognostic role of neutrophilia, lymphocytopenia and the neutrophil-to-lymphocyte ratio (NLR), and to design models to define the prognosis of patients receiving first-line chemo- or targeted therapy for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analysed 401 consecutive patients with advanced NSCLC treated with first line chemo- or targeted therapy. Patients were stratified into two groups with pre-treatment NLR ≥ 3.7 (Group A) vs. < 3.7 (Group B). The best NLR cut-off was identified by ROC curve analysis. RESULTS: At baseline 264 patients had NLR≥3.7 (Group A), whilst 137 had lower NLR (Group B). Median OS was 10.8 months and 19.4 months in the two groups (p < 0.001), while median PFS was 3.6 months and 5.6 months, respectively (p = 0.012). At multivariate analysis, ECOG-PS≥2, stage IV cancer, non-adenocarcinoma histology, EGFR wild-type status and NLR were predictors of worse OS. Stage IV cancer, wild type EGFR status and NLR≥3.7 were independent prognostic factors for worse PFS. Patients were stratified according to the presence of 0-1 prognostic factors (8%), 2-3 factors (73%) and 4-5 factors (19%) and median OS in these groups was 33.7 months, 14.6 months and 6.6 months, respectively (p < 0.001). Similarly, patients were stratified for PFS based on the presence of 0-1 prognostic factor (15%), 2 factors (41%) and 3 factors (44%). The median PFS was 8.3 months, 4.6 months and 3.3 months respectively (p < 0.001). CONCLUSIONS: Pre-treatment NLR is an independent prognostic factor for patients with advanced NSCLC treated with first-line therapies.

Clinical and pathologic predictors of clinical outcome of malignant pleural mesothelioma.

AIMS AND BACKGROUND: Although worldwide use of asbestos has decreased, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next few decades. A number of scoring systems has been proposed to assess clinicopathologic features and to predict the prognosis. We assessed the relationship between patients' features and disease evolution in order to choose the best treatment able to prolong overall survival (OS) and progression-free survival (PFS). METHODS: We retrospectively analyzed patients with locally advanced or metastatic MPM, treated at the Department of Medical Oncology, Università Politecnica Marche, Italy, from January 2003 to September 2013. Data on age, sex, smoking history, asbestos exposure, performance status, tumor stage, histology, type of treatment, and routine laboratory tests including complete blood count panel, date of death, or censored status were collected. The OS and PFS were estimated using Kaplan-Meier method and Cox analysis was performed to analyze the prognostic relevance of clinical parameters. RESULTS: We enrolled a total of 62 patients. Univariate analysis showed that histologic type, performance status, response to first-line therapy, pretreatment hemoglobin levels, and plasmatic Ca125 were significant prognostic factors. Conversely, no significant correlation was found between age, sex, smoking history, reported exposure to asbestos, stages at diagnosis, treatments, and OS and PFS. CONCLUSIONS: Our results showed that anemia and increased Ca125 might be considered negative prognostic parameters in MPM patients and confirmed the prognostic role of histotype, performance status, and response to first-line chemotherapy.

Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy--A literature review.

Neuroendocrine tumors of the gastro-entero-pancreatic system (GEP-NETs) are a heterogeneous group of neoplasms, with different malignant potential and behavior. Many treatment options are available. Surgery should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs, useful for symptoms control in functioning tumors, are also effective to inhibit tumor progression in specific settings. The multi-TKI sunitinib and of the mTOR-inhibitor everolimus are efficacy for metastatic pancreatic NET (P-NET) treatment. Chemotherapy is generally used in symptomatic and progressive NETs. Peptide receptor radionuclide therapy (PRRT) should be recommended after failure of medical therapy. For tumors confined to the liver ablative techniques should be considered. Nevertheless a shared therapeutic sequence for GEP-NET treatment still does not exist. In this review, we analyzed available data trying to identify the better treatment strategy and to suggest potential therapeutic algorithms distinguishing P-NETs from gastrointestinal NETs (GI-NETs).

Impact of VEGF, VEGFR, PDGFR, HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy.

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.

Pre-treatment neutrophil to lymphocyte ratio may be a useful tool in predicting survival in early triple negative breast cancer patients.

BACKGROUND: There is a growing body of evidence that immune response plays a large role in cancer outcome. The neutrophil to lymphocyte ratio (NLR) has been used as a simple parameter of systemic inflammation in several tumors. The purpose was to investigate the association between pre-treatment NLR, disease-free survival and overall survival in patients with early triple negative breast cancer (TNBC). METHODS: We reviewed the records of patients with stage I-III TNBC at our Institution from 2006 to 2012. The association between pre-treatment NLR and survival was analyzed. The difference among variables was calculated by chi-square test. DFS and OS were estimated using Kaplan-Meier method. Cox analysis was performed to analyze clinical parameters for their prognostic relevance. RESULTS: A total of 90 patients were eligible. There was no significant correlation among pre-treatment NLR and various clinical pathological factors. Patients with NLR higher than 3 showed significantly lower DFS (p = 0.002) and OS (p = 0.009) than patients with NLR equal or lower than 3. The Cox proportional multivariate hazard model revealed that higher pre-treatment NLR was independently correlated with poor DFS and OS, with hazard ratio 5.15 (95% confidence interval [CI] 1.11-23.88, p = 0.03) and 6.16 (95% CI 1.54-24.66, p = 0.01) respectively. CONCLUSION: Our study suggests that pre-treatment NLR may be associated with DFS and OS patients with early TNBC. Further validation and a feasibility study are required before it can be considered for clinical use.

Eribulin in heavily pretreated metastatic breast cancer patients and clinical/biological feature correlations: impact on the practice.

AIM: This multicenter study describes the effectiveness of eribulin in current practice. PATIENTS & METHODS: In total, 78 patients with advanced metastatic breast cancer, previously treated with two or more chemotherapy lines were enrolled. RESULTS: The median duration of response and disease stability were 7.5 (5.4-9.5) and 8.9 (6.2-11.6) months, respectively, with a clinical benefit (CB) at 6 months in 41% of patients. CB in visceral and nonvisceral metastases were 72.7 and 88.9%, respectively. Eribulin was active also in brain metastases, with 47% CB. The activity was shown in all biological subtypes. Toxicities were manageable. CONCLUSION: Our study confirms the effectiveness of eribulin mesylate in the treatment of patients with metastatic breast cancer and two or more lines of chemotherapy, in particular in the good disease control at the different metastatic sites.

Chromium exposure and germinal embryonal carcinoma: first two cases and review of the literature.

The aim of the study was to determine the potential role of occupational exposures to chromium (Cr) in the onset of extragonadal germinal embryonal carcinoma. The first two cases of workers in a company with Cr exposure are reported. The published scientific literature regarding the topic in peer-reviewed journals including MEDLINE and CancerLit databases was extensively reviewed. Two young patients who were coworkers in the same company, exposed to Cr, developed extragonadal germinal embryonal carcinomas. One of them also developed angiosarcoma of the mediastinum. To the best of our knowledge these are the first two cases of germinal embryonal carcinoma in patients with occupational exposure to Cr.

Androgen receptor expression in early triple-negative breast cancer: clinical significance and prognostic associations.

BACKGROUND: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. PATIENTS AND METHODS: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. RESULTS: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). CONCLUSIONS: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

Thymic neoplasms: an update on the use of chemotherapy and new targeted therapies. A literature review.

Thymic malignancies represent a wide range of clinical, histological and molecular entities, with probably considerable heterogeneity even among tumors of the same histotype. Systemic chemotherapy with cisplatin-based regimens continues to represent the standard of care in metastatic or inoperable refractory/recurrent diseases and ADOC regimen (including cisplatin, doxorubicin, vincristine and cyclophosphamide) demonstrated the longer overall response rate and median survival in the first line setting, although no randomized trial is available; and there is still a lack of standard treatment after first-line failure. To date research efforts are focused on translational studies on molecular pathways involved in thymic tumors carcinogenesis, aimed to better understand and predict the efficacy of chemotherapy and targeted therapy. Recent molecular characterization includes identification of a number of oncogenes, tumor suppressor genes, chromosomal aberrations, angiogenic factors, and tumor invasion factors involved in cellular survival and proliferation and in tumor growth. The use of biologic drugs is currently not recommended in a routine practice because there are limited data on their therapeutic role in thymic epitelial tumors. Because of the lack of data from adequate-sized, prospective trials are required for validation and the enrolment of patients with advanced disease into available clinical trials has to be encouraged.