Case series of trans-thoracic nodule aspirate performed by interventional pulmonologists

Percutaneous interventional tissue sampling of pulmonary masses and lymphadenopathy is a means for diagnosis of thoracic malignancy. The user base that can perform this skill with ultrasound guidance is expanding. A retrospective cohort of fine needle aspiration and percutaneous core biopsies was identified to evaluate their safety and efficacy. 47 distinct procedures were performed by a university medical center\u27s Interventional Pulmonary service between 2012 and 2018.39 consecutive procedures were diagnostically successful by percutaneous means, with 34 of the successful diagnoses based on fine needle aspiration alone. In our cohort by percutaneous biopsy the most common diagnosis was Non-Small Cell Lung Cancer with 28 samples, followed by Small Cell Lung Cancer with 7 samples as well as additional solitary diagnoses of suspected infection, Hepatocellular Cancer, Hodgkin Lymphoma and Malignant Melanoma. 4 procedures had complications, two of which resolved post procedure with observation and two pneumothoracies which resolved with chest tube placement and hospital observation. A wide variety of diagnoses were obtained with percutaneous biopsies with 83% of percutaneous biopsies performed by Interventional Pulmonologists achieving diagnostic success

Molecular phenotypes in triple negative breast cancer from African American patients suggest targets for therapy.

Triple negative breast cancer (TNBC) is characterized by high proliferation, poor differentiation and a poor prognosis due to high rates of recurrence. Despite lower overall incidence African American (AA) patients suffer from higher breast cancer mortality in part due to the higher proportion of TNBC cases among AA patients compared to European Americans (EA). It was recently shown that the clinical heterogeneity of TNBC is reflected by distinct transcriptional programs with distinct drug response profiles in preclinical models. In this study, gene expression profiling and immunohistochemistry were used to elucidate potential differences between TNBC tumors of EA and AA patients on a molecular level. In a retrospective cohort of 136 TNBC patients, a major transcriptional signature of proliferation was found to be significantly upregulated in samples of AA ethnicity. Furthermore, transcriptional profiles of AA tumors showed differential activation of insulin-like growth factor 1 (IGF1) and a signature of BRCA1 deficiency in this cohort. Using signatures derived from the meta-analysis of TNBC gene expression carried out by Lehmann et al., tumors from AA patients were more likely of basal-like subtypes whereas transcriptional features of many EA samples corresponded to mesenchymal-like or luminal androgen receptor driven subtypes. These results were validated in The Cancer Genome Atlas mRNA and protein expression data, again showing enrichment of a basal-like phenotype in AA tumors and mesenchymal subtypes in EA tumors. In addition, increased expression of VEGF-activated genes together with elevated microvessel area determined by the AQUA method suggest that AA patients exhibit higher tumor vascularization. This study confirms the existence of distinct transcriptional programs in triple negative breast cancer in two separate cohorts and that these programs differ by racial group. Differences in TNBC subtypes and levels of tumor angiogenesis in AA versus EA patients suggest that targeted therapy choices should be considered in the context of race

Representative histospots depicting microvessel area (MVA) and expression of angiogenesis markers.

<p>Panels (A) and (B) show cytokeratin staining for determination of the tumor area in red, DAPI-stained nuclei in blue and CD31-positive microvessel area in green. Panel A depicts a representative histospot from a European American sample, panel B shows a representative African American sample. (C) Proportion of African American and European American patients with large microvessel area (more than 0.6%, hatched bars) (D) Expression ranks of 11 VEGF-activated genes <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071915#pone.0071915-Hu1" target="_blank">[19]</a> in African American and European American samples.</p

Association of ethnicity with TNBC subtypes [<b>9</b>].

<p>Correlations of gene expression with the mesenchymal stem cell (A), luminal androgen receptor positive (B) and basal 1 (C) subtypes were compared between African American (AA) and European American (EA) patient samples.</p

Associations of ethnicity with published gene expression signatures.

<p>Signatures of (A) <i>BRCA1</i> deficiency <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071915#pone.0071915-VantVeer1" target="_blank">[37]</a> (B) genomic grade <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071915#pone.0071915-Sotiriou1" target="_blank">[17]</a> and (C) IGF1 ligand activation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071915#pone.0071915-Mu1" target="_blank">[18]</a> were compared between African American (AA) and European American (EA) patient samples.</p

Gene sets positively associated with principal component 4 by enrichment analysis.

<p>Enrichment of gene sets from the Broad Molecular Signature Database (MSigDB) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071915#pone.0071915-Subramanian1" target="_blank">[34]</a>, Gene Ontology <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071915#pone.0071915-Ashburner1" target="_blank">[33]</a> and selected publications was assessed using Fisher's Exact test for 250 probes with the highest projection scores on principal component 4. P-values were FDR-adjusted for multiple testing.</p

Differential projection scores on principal component 4 by ethnicity.

<p>Differential projection scores on principal component 4 by ethnicity.</p

Clinical characteristics of the Yale TNBC cohort.

<p>Percentages refer to the total number of cases with available data.</p