Targeted biopsy added to systematic biopsy improves cancer detection in prostate cancer screening.

BACKGROUND: Magnetic resonance imaging (MRI)/ultrasound targeted biopsy has frequently been used together with a 12-core systematic biopsy for prostate cancer screening in the past few years. However, the efficacy of targeted biopsy compared to systematic biopsy, as well as its clinical-histologic correlation, has been assessed by a limited number of studies and is further investigated in this study. DESIGN: We collected 960 cases with both targeted and systematic prostate biopsies from 04/2019 to 04/2022 (Table 1). We compared cancer detection rates between targeted and systematic prostate biopsies in different grade groups. Correlations with the size of prostate lesions, prostate-specific antigen (PSA) level, and Prostate Imaging-Reporting and Data System (PI-RADS) scale were also analyzed for each of these biopsy methods. RESULTS: Among the 960 men who underwent targeted biopsy with systematic biopsy, prostatic adenocarcinoma was diagnosed in 652 (67.9%) cases. 489 (50.9%) cases were diagnosed by targeted biopsy and 576 (60.0%) cases were diagnosed by systematic biopsy. In the 384 cases diagnosed negative by systematic biopsy, targeted biopsy identified cancer in 76 (8%) cases. Systematic biopsy was able to detect 163 cancer cases that were missed by targeted biopsy. Systematic biopsy detected more grade group 1 cancers compared to targeted biopsy. However, for higher grade cancers, the differences between the cancer detection rates of targeted biopsy and systematic biopsy became negligible. Targeted biopsy upgraded the grade group categorized by systematic biopsy in several cases (3.8%, 7.0%, 2.6%, 1.1% and 0.9% in Grade Groups 1, 2, 3, 4, and 5 respectively). Targeted biopsy was more likely to detect cancer in larger lesions (13.17 mm VS 11.41 mm, P=0.0056) and for higher PI-RADS scales (4.19 VS 3.68, P<0.0001). The cancers detected by targeted biopsy also had higher PSA levels (10.38 ng/ml VS 6.39 ng/ml, P=0.0026). CONCLUSION: Targeted biopsy with systematic biopsy improved cancer detection rate compared to systematic biopsy alone. Targeted biopsy is not more sensitive for grade groups 1, 4, or 5 cancers but is as sensitive as systematic biopsy for detecting grade group 2 and 3 cancers. Targeted biopsy is more effective at detecting cancers when patients have larger lesions, higher PI-RADS scales, and higher PSA levels.

Genomic and transcriptomic analysis of a library of small cell lung cancer patient-derived xenografts.

Access to clinically relevant small cell lung cancer (SCLC) tissue is limited because surgical resection is rare in metastatic SCLC. Patient-derived xenografts (PDX) and circulating tumor cell-derived xenografts (CDX) have emerged as valuable tools to characterize SCLC. Here, we present a resource of 46 extensively annotated PDX/CDX models derived from 33 patients with SCLC. We perform multi-omic analyses, using targeted tumor next-generation sequencing, RNA-sequencing, and immunohistochemistry to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these SCLC models. SCLC subtypes characterized by transcriptional regulators, ASCL1, NEUROD1 and POU2F3 are confirmed in this cohort. A subset of SCLC clinical specimens, including matched PDX/CDX and clinical specimen pairs, confirm that the primary features and genomic and proteomic landscapes of the tumors of origin are preserved in the derivative PDX models. This resource provides a powerful system to study SCLC biology.

MAPK pathway activation selectively inhibits ASCL1-driven small cell lung cancer.

Activation of mitogenic signaling pathways is a common oncogenic driver of many solid tumors including lung cancer. Although activating mutations in the mitogen-activated protein kinase (MAPK) pathway are prevalent in non-small cell lung cancers, MAPK pathway activity, counterintuitively, is relatively suppressed in the more aggressively proliferative small cell lung cancer (SCLC). Here, we elucidate the role of the MAPK pathway and how it interacts with other signaling pathways in SCLC. We find that the most common SCLC subtype, SCLC-A associated with high expression of ASCL1, is selectively sensitive to MAPK activation in vitro and in vivo through induction of cell-cycle arrest and senescence. We show strong upregulation of ERK negative feedback regulators and STAT signaling upon MAPK activation in SCLC-A lines. These findings provide insight into the complexity of signaling networks in SCLC and suggest subtype-specific mitogenic vulnerabilities.

Multimodality imaging findings of visceral myopathy in a child presenting with palpable abdominal mass.

Bayramoglu Z, Yilmaz R, Demir AA, Ataizi-Çelikel Ç, Kombak FE, Ikinci A, Yekeler E. Multimodality imaging findings of visceral myopathy in a child presenting with palpable abdominal mass. Turk J Pediatr 2019; 61: 120-125. Visceral myopathy is a rare cause of intestinal obstruction characterized by intestinal dysmotility and constipation. Patients often present with recurrent abdominal pain, vomiting and abdominal distension. We report a rare case of visceral myopathy in a child presenting with intraabdominal mass. We aimed to describe ultrasound, computed tomography and magnetic resonance enterography findings of this rare disease that has not been demonstrated before. Differential diagnosis of mural thickening with distinguishable layers in addition to intestinal dilatation in the absence of mesenteric inflammation includes visceral myopathy.

BRAFV600E Immunohistochemistry in Papillary Thyroid Carcinomas: Relationship Between Clinical and Morphological Parameters.

OBJECTIVE: To investigate the association of the BRAFV600E mutation with papillary thyroid carcinoma using clinical, morphological and prognostic parameters. We also intend to assess the utility of the BRAFV600E immunohistochemistry and compare it with BRAF polymerase chain reaction (RT-PCR). MATERIAL AND METHOD: We applied BRAFV600E immunohistochemistry in a cohort of 107 papillary carcinomas, 19 adenomas and 13 normal thyroid tissues that was chosen retrospectively between 2011 and 2015. Statistical analysis was based on semiquantitative immunohistochemistry findings. We also applied BRAF RT-PCR in a subgroup of 14 papillary carcinomas, 13 metastatic lymph nodes and 4 adenomas that was chosen randomly. RESULTS: In regard to the comparison of BRAFV600E immunohistochemistry and BRAF RT-PCR, a 3+ nuclear and cytoplasmic immunoexpression was considered 'positive'. The BRAFV600E mutation was most frequently observed in classic variant cases. No mutation was detected in follicular variant cases. The mutational status of the primary tumour and the lymph node metastasis was consistent. A significant relationship of the BRAFV600E mutation was found with prognostic factors such as higher pT stage, classic variant, lymphatic invasion, perineural invasion, lower mitotic index, lack of tumour capsule, intrathyroidal spread and extrathyroidal extension. CONCLUSION: Immunohistochemistry, using the VE1 clone, is a reliable technique for detection of the BRAFV600E mutation. Our results with immunohistochemistry are consistent with a previous effort. In our study, despite the correlation between some pathological prognostic parameters and the BRAFV600E mutation; poor prognosis was found to be irrelevant overall. Morphological parameters seem to be keener than the BRAFV600E mutation. Nevertheless, different series display different results, possibly due to environmental factors. Considering this and the proven success of targeted therapies against the BRAFV600E mutation a thorough assessment would be important.

Concordance of immunohistochemistry between core needle biopsy and surgical resection of breast cancer

Background/aim: The purpose of this study was to evaluate the concordance of immunohistochemical (IHC) parameters of breast lesions between the core needle biopsy (CNB) and the surgical resection specimen. Materials and methods: CNB and resection specimens of female patients were retrospectively analyzed. ER, PR, HER-2, and Ki-67 parameters were compared for each patient. A total of 284 cases were assessed. Forty-one and 48 cases were excluded from the HER-2 and Ki-67 examinations, respectively, because the CNBs did not allow for IHC. Results: Concordance rates were 93.3% for ER, 89.4% for PR, 90.1% for HER-2, and 80.9% for Ki-67.Conclusion: CNB is accurate for the evaluation of the surrogate molecular profile of invasive breast cancer despite the heterogeneity of tumors.

Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma.

New strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1% aerosolized OVA. 5×10(5) ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice.

Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (P<0.001). Intravenous administration of mCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (P<0.001). We showed that GFP-labeled MSCs were located in the lungs of OVA group 2weeks after intravenous induction. mCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA+MSC group) (P<0.037). Our studies revealed that mCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma.