Prognostic Model for High-Grade Neuroendocrine Carcinoma of the Lung Incorporating Genomic Profiling and Poly (ADP-ribose) Polymerase-1 Expression.

PURPOSE: High-grade neuroendocrine carcinoma (HGNEC) of the lung is an aggressive cancer with a complex biology. We aimed to explore the prognostic value of genetic aberrations and poly(ADP-ribose) polymerase-1 (PARP1) expression in HGNEC and to establish a novel prognostic model. MATERIALS AND METHODS: We retrospectively enrolled 191 patients with histologically confirmed HGNEC of the lung. Tumor tissues were analyzed using PARP1 immunohistochemistry (IHC; N = 191) and comprehensive cancer panel sequencing (n = 102). Clinical and genetic data were used to develop an integrated Cox hazards model. RESULTS: Strong PARP1 IHC expression (intensity 3) was observed in 153 of 191 (80.1%) patients, and the mean PARP1 H-score was 285 (range, 5-300). To develop an integrated Cox hazard model, our data set included information from 357 gene mutations and 19 clinical profiles. When the targeted mutation profiles were combined with clinical profiles, 12 genes (ATRX, CCND2, EXT2, FGFR2, FOXO1, IL21R, MAF, TGM7, TNFAIP3, TP53, TSHR, and DDR2) were identified as prognostic factors for survival. The integrated Cox hazard model, which combines mutation profiles with a baseline model, outperformed the baseline model (incremental area under the curve 0.84 v 0.78; P = 8.79e-12). The integrated model stratified patients into high- and low-risk groups with significantly different disease-free and overall survival (integrated model: hazard ratio, 7.14 [95% CI, 4.07 to 12.54]; P < .01; baseline model: 4.38 [2.56 to 7.51]; P < .01). CONCLUSION: We introduced a new prognostic model for HGNEC that combines genetic and clinical data. The integrated Cox hazard model outperformed the baseline model in predicting the survival of patients with HGNEC.

Synchrotron Radiation Refraction-Contrast Computed Tomography Based on X-ray Dark-Field Imaging Optics of Pulmonary Malignancy: Comparison with Pathologic Examination.

Refraction-contrast computed tomography based on X-ray dark-field imaging (XDFI) using synchrotron radiation (SR) has shown superior resolution compared to conventional absorption-based methods and is often comparable to pathologic examination under light microscopy. This study aimed to investigate the potential of the XDFI technique for clinical application in lung cancer diagnosis. Two types of lung specimens, primary and secondary malignancies, were investigated using an XDFI optic system at beamline BL14B of the High-Energy Accelerator Research Organization Photon Factory, Tsukuba, Japan. Three-dimensional reconstruction and segmentation were performed on each specimen. Refraction-contrast computed tomographic images were compared with those obtained from pathological examinations. Pulmonary microstructures including arterioles, venules, bronchioles, alveolar sacs, and interalveolar septa were identified in SR images. Malignant lesions could be distinguished from the borders of normal structures. The lepidic pattern was defined as the invasive component of the same primary lung adenocarcinoma. The SR images of secondary lung adenocarcinomas of colorectal origin were distinct from those of primary lung adenocarcinomas. Refraction-contrast images based on XDFI optics of lung tissues correlated well with those of pathological examinations under light microscopy. This imaging method may have the potential for use in lung cancer diagnosis without tissue damage. Considerable equipment modifications are crucial before implementing them from the lab to the hospital in the near future.

Morc2a variants cause hydroxyl radical-mediated neuropathy and are rescued by restoring GHKL ATPase.

Mutations in the Microrchidia CW-Type Zinc Finger 2 (MORC2) GHKL ATPase module cause a broad range of neuropathies, such as Charcot-Marie-Tooth disease type 2Z; however, the aetiology and therapeutic strategy are not fully understood. Previously, we reported that the Morc2a p.S87L mouse model exhibited neuropathy and muscular dysfunction through DNA damage accumulation. In the present study, we analysed the gene expression of Morc2a p.S87L mice and designated the primary causing factor. We investigated the pathological pathway using Morc2a p.S87L mouse embryonic fibroblasts and human fibroblasts harbouring MORC2 p.R252W. We subsequently assessed the therapeutic effect of gene therapy administered to Morc2a p.S87L mice. This study revealed that Morc2a p.S87L causes a protein synthesis defect, resulting in the loss of function of Morc2a and high cellular apoptosis induced by high hydroxyl radical levels. We considered the Morc2a GHKL ATPase domain as a therapeutic target because it simultaneously complements hydroxyl radical scavenging and ATPase activity. We used the adeno-associated virus (AAV)-PHP.eB serotype, which has a high central nervous system transduction efficiency, to express Morc2a or Morc2a GHKL ATPase domain protein in vivo. Notably, AAV gene therapy ameliorated neuropathy and muscular dysfunction with a single treatment. Loss of functional characteristics due to protein synthesis defects in Morc2a p.S87L was also noted in human MORC2 p.S87L or p.R252W variants, indicating the correlation between mouse and human pathogenesis. In summary, CMT2Z is known as an incurable genetic disorder, but the present study demonstrated its mechanisms and treatments based on established animal models. This study demonstrates that the Morc2a p.S87L variant causes hydroxyl radical-mediated neuropathy, which can be rescued through AAV-based gene therapy.

In vivo genome editing using 244-cis LNPs and low-dose AAV achieves therapeutic threshold in hemophilia A mice.

Gene therapy and rebalancing therapy have emerged as promising approaches for treating hemophilia A, but there are limitations, such as temporary efficacy due to individual differences. Genome editing for hemophilia has shown long-term therapeutic potential in preclinical trials. However, a cautious approach is necessary because genome editing is irreversible. Therefore, we attempted to induce low-level human factor 8 (hF8) gene knockin (KI) using 244-cis lipid nanoparticles and low-dose adeno-associated virus to minimize side effects and achieve a therapeutic threshold in hemophilia A mice. We selected the serpin family C member 1, SerpinC1, locus as a target to enable a combined rebalancing strategy with hF8 KI to augment efficacy. This strategy improved blood coagulation activity and reduced hemophilic complications without adverse effects. Furthermore, hemophilic mice with genome editing exhibit enhanced survival for 40 weeks. Here, we demonstrate an effective, safe, and sustainable treatment for hemophilia A. This study provides valuable information to establish safe and long-term genome-editing-mediated treatment strategies for treating hemophilia and other protein-deficient genetic diseases.

Design of Pore Properties of an Al-Based Metal-Organic Framework for the Separation of an Ethane/Ethylene Gas Mixture via Ethane-Selective Adsorption.

A series of Al-based isomorphs (CAU-10H, MIL-160, KMF-1, and CAU-10pydc) were synthesized using isophthalic acid (ipa), 2,5-furandicarboxylic acid (fdc), 2,5-pyrrole dicarboxylic acid (pyrdc), and 3,5-pyridinedicarboxylic acid (pydc), respectively. These isomorphs were systematically investigated to identify the best adsorbent for effectively separating C2H6/C2H4. All CAU-10 isomorphs exhibited preferential adsorption of C2H6 over that of C2H4 in mixture. CAU-10pydc exhibited the best C2H6/C2H4 selectivity (1.68) and the highest C2H6 uptake (3.97 mmol g-1) at 298 K and 1 bar. In the breakthrough experiment using CAU-10pydc, 1/1 (v/v) and 1/15 (v/v) C2H6/C2H4 gas mixtures were successfully separated into high-purity C2H4 (>99.95%), with remarkable productivities of 14.0 LSTP kg-1 and 32.0 LSTP kg-1, respectively, at 298 K. Molecular simulations revealed that the exceptional separation performance of CAU-10pydc originated from the increased porosity and reduced electron density of the pyridine ring of pydc, leading to a relatively larger decrease in π-π interactions with C2H4 than in the C-H···π interactions with C2H6. This study demonstrates that the pore size and geometry of the CAU-10 platform are modulated by the inclusion of heteroatom-containing benzene dicarboxylate or heterocyclic rings of dicarboxylate-based organic linkers, thereby fine-tuning the C2H6/C2H4 separation ability. CAU-10pydc was determined to be an optimum adsorbent for this challenging separation.

Uniform Gold Nanostructure Formation via Weakly Adsorbed Gold Films and Thermal Annealing for Reliable Localized Surface Plasmon Resonance-Based Detection of DNase-I.

Deoxyribonuclease-I (DNase-I), a representative endonuclease, is an important biomarker for the diagnosis of infectious diseases and cancer progression. However, enzymatic activity decreases rapidly ex vivo, which highlights the need for precise on-site detection of DNase-I. Here, a localized surface plasmon resonance (LSPR) biosensor that enables the simple and rapid detection of DNase-I is reported. Moreover, a novel technique named electrochemical deposition and mild thermal annealing (EDMIT) is applied to overcome signal variations. By taking advantage of the low adhesion of gold clusters on indium tin oxide substrates, both the uniformity and sphericity of gold nanoparticles are increased under mild thermal annealing conditions via coalescence and Ostwald ripening. This ultimately results in an approximately 15-fold decrease in LSPR signal variations. The linear range of the fabricated sensor is 20-1000 ng mL-1 with a limit of detection (LOD) of 127.25 pg mL-1 , as demonstrated by spectral absorbance analyses. The fabricated LSPR sensor stably measured DNase-I concentrations from samples collected from both an inflammatory bowel disease (IBD) mouse model, as well as human patients with severe COVID-19 symptoms. Therefore, the proposed LSPR sensor fabricated via the EDMIT method can be used for early diagnosis of other infectious diseases.

In vivo genome editing for hemophilia B therapy by the combination of rebalancing and therapeutic gene knockin using a viral and non-viral vector.

Recent therapeutic strategies for hemophilia include long-term therapeutic gene expression using adeno-associated virus (AAV) and rebalancing therapy via the downregulation of anticoagulant pathways. However, these approaches have limitations in immune responses or insufficiency to control acute bleeding. Thus, we developed a therapeutic strategy for hemophilia B by a combined rebalancing and human factor 9 (hF9) gene knockin (KI) using a lipid nanoparticle (LNP) and AAV. Antithrombin (AT; Serpin Family C Member 1 [Serpinc1]) was selected as the target anticoagulation pathway for the gene KI. First, the combined use of LNP-clustered regularly interspaced short palindromic repeats (CRISPR) and AAV donor resulted in 20% insertions or deletions (indels) in Serpinc1 and 67% reduction of blood mouse AT concentration. Second, hF9 coding sequences were integrated into approximately 3% of the target locus. hF9 KI yielded approximately 1,000 ng/mL human factor IX (hFIX) and restored coagulation activity to a normal level. LNP-CRISPR injection caused sustained AT downregulation and hFIX production up to 63 weeks. AT inhibition and hFIX protein-production ability could be maintained by the proliferation of genetically edited hepatocytes in the case of partial hepatectomy. The co-administration of AAV and LNP showed no severe side effects except random integrations. Our results demonstrate hemophilia B therapy by a combination of rebalancing and hF9 KI using LNP and AAV.

Granular Cell Tumor Originating from the Pectoral Muscle: A Rare Extramammary Finding on Mammography.

A granular cell tumor (GCT) is a rare soft tissue tumor that usually arises from the striated muscle of the tongue. Few literatures have reported pectoral muscle involvement of the GCT. Herein, we report a rare case of a GCT originating from the pectoral muscle below the breast with multimodal imaging appearance.

BCI-215, a Dual-Specificity Phosphatase Inhibitor, Reduces UVB-Induced Pigmentation in Human Skin by Activating Mitogen-Activated Protein Kinase Pathways.

BACKGROUND: The dysregulation of melanin production causes skin-disfiguring ultraviolet (UV)-associated hyperpigmented spots. Previously, we found that the activation of c-Jun N-terminal kinase (JNK), a mitogen-activated protein kinase (MAPK), inhibited melanogenesis. METHODS: We selected BCI-215 as it may modify MAPK expression via a known function of a dual-specificity phosphatase (DUSP) 1/6 inhibitor. B16F10 melanoma cells, Mel-ab cells, human melanocytes, and a coculture were used to assess the anti-melanogenic activity of BCI-215. The molecular mechanisms were deciphered by assaying the melanin content and cellular tyrosinase activity via immunoblotting and RT-PCR. RESULTS: BCI-215 was found to suppress basal and cAMP-stimulated melanin production and cellular tyrosinase activity in vitro through the downregulation of microphthalmia-associated transcription factor (MITF) protein and its downstream enzymes. The reduction in MITF expression caused by BCI-215 was found to be due to all three types of MAPK activation, including extracellular signal-regulated kinase (ERK), JNK, and p38. The degree of activation was greater in ERK. A phosphorylation of the ß-catenin pathway was also demonstrated. The melanin index, expression of MITF, and downstream enzymes were well-reduced in UVB-irradiated ex vivo human skin by BCI-215. CONCLUSIONS: As BCI-215 potently inhibits UV-stimulated melanogenesis, small molecules of DUSP-related signaling modulators may provide therapeutic benefits against pigmentation disorders.

Genome editing-mediated knock-in of therapeutic genes ameliorates the disease phenotype in a model of hemophilia.

Recently, clinical trials of adeno-associated virus-mediated replacement therapy have suggested long-term therapeutic effects for several genetic diseases of the liver, including hemophilia. However, there remain concerns regarding decreased therapeutic effects when the liver is regenerated or when physiological proliferation occurs. Although genome editing using the clustered regularly interspaced short palindromic repeats/Cas9 system provides an opportunity to solve this problem, low knock-in efficiency may limit its application for therapeutically relevant expression. Here, we identified a novel gene, APOC3, in which a strong promoter facilitated the expression of knocked-in genes in hepatocytes. We also investigated the effects of APOC3 editing using a small Cas9 protein derived from Campylobacter jejuni (CjCas9) in a hemophilic model. We demonstrated that adeno-associated virus-mediated delivery of CjCas9 and donor led to moderate levels of human factor 9 expression in APOC3-humanized mice. Moreover, knock-in-driven expression induced substantial recovery of clotting function in mice with hemophilia B. There was no evidence of off-target editing in vitro or in vivo. Collectively, our findings demonstrated therapeutically relevant expression using a precise and efficient APOC3-editing platform, providing insights into the development of further long-term therapeutics for diverse monogenic liver diseases.

Concordance between biparametric MRI, transperineal targeted plus systematic MRI-ultrasound fusion prostate biopsy, and radical prostatectomy pathology.

We aimed to confirm the reliability of the results of bi-parametric magnetic resolution imaging-ultrasound fusion targeted and systematic biopsies (bpMRI-US transperineal FTSB) compared to prostatectomy specimens. We retrospectively analyzed the records of 80 men who underwent bpMRI-US transperineal FTSB with region of interest (ROI) and subsequent robot-assisted radical prostatectomy. Changes in the grade group determined by MRI and biopsy versus surgical specimens were analyzed. Thirty-five patients with insignificant prostate cancer and 45 with significant cancer were diagnosed using bpMRI-US transperineal FTSB. Among those with insignificant PCa, 25 (71.4%) were upgraded to significant PCa in prostatectomy specimens: 9/12 (75.0%) with Prostate Imaging Reporting and Data System (PI-RADS) 3, 12/16 (75.0%) with PI-RADS 4, and 4/7 (57.1%) with PI-RADS 5. In the PI-RADS 3 group, the upgraded group showed higher prostate specific antigen (PSA) and PSA density (PSAD) than the concordance group; PSA 8.34(2.73) vs. 5.31(2.46) (p = 0.035) and PSAD 0.29(0.11) vs. 0.18(0.09) (p = 0.025). The results of prostate biopsy and prostatectomy specimens were inconsistent and underestimated in patients with MRI-visible lesions. Therefore, for precise and individualized treatment strategies for PCa with MRI-visible lesions, careful interpretation of biopsy result is required.

Clustering subtypes of breast cancer by combining immunohistochemistry profiles and metabolism characteristics measured using FDG PET/CT.

BACKGROUND: The aim of this study was to investigate the effect of combining immunohistochemical profiles and metabolic information to characterize breast cancer subtypes. METHODS: This retrospective study included 289 breast tumors from 284 patients who underwent preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography/ computed tomography (PET/CT). Molecular subtypes of breast cancer were classified as Hormonal, HER2, Dual (a combination of both Hormonal and HER2 features), and triple-negative (TN). Histopathologic findings and immunohistochemical results for Ki-67, EGFR, CK 5/6, and p53 were also analyzed. The maximum standardized uptake value (SUV) measured from FDG PET/CT was used to evaluate tumoral glucose metabolism. RESULTS: Overall, 182, 24, 47, and 36 tumors were classified as Hormonal, HER2, Dual, and TN subtypes, respectively. Molecular profiles of tumor aggressiveness and the tumor SUV revealed a gradual increase from the Hormonal to the TN type. The tumor SUV was significantly correlated with tumor size, expression levels of p53, Ki-67, and EGFR, and nuclear grade (all p < 0.001). In contrast, the tumor SUV was negatively correlated with the expression of estrogen receptors (r = - 0.234, p < 0.001) and progesterone receptors (r = - 0.220, p < 0.001). Multiple linear regression analysis revealed that histopathologic markers explained tumor glucose metabolism (adjusted R-squared value 0.238, p < 0.001). Tumor metabolism can thus help define breast cancer subtypes with aggressive/adverse prognostic features. CONCLUSIONS: Metabolic activity measured using FDG PET/CT was significantly correlated with the molecular alteration profiles of breast cancer assessed using immunohistochemical analysis. Combining molecular markers and metabolic information may aid in the recognition and understanding of tumor aggressiveness in breast cancer and be helpful as a prognostic marker.

Synchrotron Radiation-Based Refraction-Contrast Tomographic Images Using X-ray Dark-Field Imaging Optics in Human Lung Adenocarcinoma and Histologic Correlations.

The aim of this study was to evaluate the clinical implication of synchrotron radiation imaging techniques for human lung adenocarcinoma in comparison with pathologic examination. A refraction-based tomographic imaging technique called the X-ray dark-field imaging (XDFI) method was used to obtain computed tomographic images of human lung adenocarcinoma at the beam line at Photon Factory BL 14B at the High Energy Accelerator Research Organization (KEK) in Tsukuba, Japan. Images of normal lung tissue were also obtained using the same methods and reconstructed as 3D images. Both reconstructed images were compared with pathologic examinations from histologic slides which were made with identical samples. Pulmonary alveolar structure including terminal bronchioles, alveolar sacs, and vasculatures could be identified in synchrotron radiation images of normal lung. Hyperplasia of interstitial tissue and dysplasia of alveolar structures were noticed in images of lung adenocarcinoma. Both synchrotron radiation images were considerably correlated with images from histologic slides. Lepidic patterns of cancer tissue were distinguished from the invasive area in synchrotron radiation images of lung adenocarcinoma. Refraction-contrast tomographic techniques using synchrotron radiation could provide high-resolution images of lung adenocarcinoma which are compatible with those from pathologic examinations.

Perioperative risk factors in surgical lung biopsy for the diagnosis of interstitial lung disease: a single-centre experience.

BACKGROUND: The aim of this study was to evaluate mortality and morbidity after surgical lung biopsy in patients with interstitial lung diseases and to investigate perioperative risk factors for complications. METHODS: A total of 132 enrolled patients were divided into three groups: group 1 (70), patients with operation scheduled before admission; group 2 (48), patients with operation determined after medical therapy; and group 3 (14), patients with emergent operation followed by steroid therapy. Complications were classified according to the Clavien-Dindo system. The 30- and 90-day mortality and complication rates were evaluated, and perioperative risk factors were investigated. RESULTS: Overall complication rate was 19.7%. The 30- and 90-day in-hospital mortality rates were 1.5% and 3.0%, respectively. Complication rates more than grade II were significantly different between the three groups (P = 0.045). Patients in group 1 revealed only class I or II complications and no mortalities. Elevated oxygen demand after operation was an independent risk factor for any complications, complications more than class II and any events (P < 0.001, P = 0.042 and P < 0.001, respectively). The New York Heart Association Functional Classification (NYHA) class IV was a statistically significant risk factor for any complications (P = 0.036, odds ratio 7.93). Higher NYHA class (III and IV) showed significantly higher risk in occurrence of any events after lung biopsy. CONCLUSION: Prepared surgical lung biopsy for interstitial lung disease is feasible with reasonable morbidity. Higher NYHA class and elevated oxygen demand after the surgery could imply post-operative outcomes. Alternative diagnostic methods such as transbronchial biopsy or bronchoalveolar lavage should be considered prior to surgical lung biopsy especially in high-risk patients.

Different Immunohistochemical Localization of Fatty Acid Binding Protein 5 in Actinic Keratosis Compared with That in Bowen's Disease: A Retrospective Study.

ABSTRACT: Actinic keratosis (AK) and Bowen's disease (BD) are common premalignant lesions of invasive squamous cell carcinoma that have different pathogenesis and clinical significance. Fatty acid-binding protein 5 (FABP5) is responsible for keratinocyte homeostasis and differentiation; however, no study has revealed its expression in AK and BD. Our study aimed to investigate the differential expression and significance of FABP5 in these lesions. Patients with pathologically confirmed cases of AK (n = 37) and BD (n = 12) were included in this study. FABP5 immunostaining pattern was assessed in the normal skin, AK and BD lesions, with a focus on the staining patterns of basal cells, atypical keratinocytes, and uninvolved epidermal keratinocytes. All patients with AK showed negative FABP5 expression in the atypical cells in the basal layer, whereas the uninvolved upper layers showed diffuse, strong FABP5 expression, regardless of the grade of AK. All patients with BD showed heterogeneous and diffuse FABP5 expression in atypical cells of all layers of the epidermis. This study is the first to investigate the role of FABP5 in premalignant skin lesions. The unique immunohistochemical localization of the FABP5 can be a helpful diagnostic marker, and altered fatty acid metabolism may be the key in understanding the different pathophysiology of AK and BD.

Clinical implication of tumour spread through air spaces in pathological stage I lung adenocarcinoma treated with lobectomy.

OBJECTIVES: The aim of this study was to evaluate the clinical implication of tumour spread through air spaces (STAS) as a prognostic factor in pathological stage I lung adenocarcinoma treated with lobectomy and to identify related parameters. METHODS: Medical records of patients who underwent pulmonary lobectomy for stage I (American Joint Committee on Cancers eighth edition) lung adenocarcinomas between 2012 and February 2018 at our institutions were reviewed retrospectively. Patients with minimally invasive adenocarcinomas and tumours ≥3 cm in size were excluded. Included patients were classified into STAS (+) and STAS (-) groups. Clinical implications of STAS and recurrence in patients were investigated. RESULTS: A total of 109 patients was analysed: 41 (37.6%) in the STAS (+) and 68 (62.4%) in the STAS (-) group. STAS was associated with larger consolidation diameter on chest tomography (≥1.5 cm; P = 0.006) or a higher invasive ratio (≥85%; P = 0.012) and presence of a micropapillary pattern in multivariable analysis (P = 0.003) The recurrence-free survival curve showed statistical difference (P = 0.008) with 3-year survival rates of 73.0% (9 patients) and 96.8% (2 patients) in the STAS (+) and STAS (-) group, respectively. However, no statistical significance was observed in the lung cancer-related survival curve (P = 0.648). The presence of STAS was an independent risk factor for recurrence in multivariable analysis (hazard ratio = 5.9, P = 0.031). CONCLUSIONS: The presence of STAS could be an important risk factor for recurrence in patients with early-stage invasive lung adenocarcinoma treated with pulmonary lobectomy.

Differences in prognosis by p53 expression after neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: Our previous studies suggested that p53-positive triple-negative breast cancer (TNBC) should be more sensitive to chemotherapy than p53-negative TNBC. The aim of this study was to determine whether p53 expression in TNBC could predict response to neoadjuvant chemotherapy and the resulting prognosis. METHODS: From January 2009 to December 2017, TNBC patients who underwent neoadjuvant chemotherapy were reviewed, including a total of 31 TNBC patients who had clinical lymph node metastasis. The status of p53 expression in patients before and after chemotherapy was evaluated. RESULTS: Two patients (22.2%, 2 of 9) achieved pCR in p53(+) TNBC and 4 patients (50%, 5 of 10) achieved pCR in p53(-) TNBC. There was no correlation between pCR rate and p53 expression (P = 0.350). Based on prechemotherapy p53 expression, there was no significant difference in disease-free survival (DFS) between p53(+) TNBC and p53(-) TNBC (P = 0.335). However, after chemotherapy, p53(+) TNBC had shown higher DFS than p53(-) TBNC (P = 0.099). Based on prechemotherapy p53 expression, p53(+) TNBC had better overall survival (OS) than p53(-) TNBC, but the difference was not statistically significant (P = 0.082). After chemotherapy, p53(+) TNBC showed significantly better OS than p53(-) TNBC (P = 0.018). CONCLUSION: Immunohistochemically detected p53 expression in TNBC could not predict the response to neoadjuvant chemotherapy. However, p53(+) TNBC had a better OS than p53(-) TNBC in patients who underwent neoadjuvant chemotherapy.

Ectopic Prostatic Tissue in the Right Paracolic Gutter: A Case Report.

Ectopic prostatic tissue (EPT) is fairly uncommon; however, when reported, it is most often found in the male genitourinary tract. Since extragenitourinary EPT is very rare, it is extremely difficult to properly diagnose preoperatively.(1-3) This article describes a unique case of EPT found in the right paracolic gutter.

BRCA1-associated protein 1 expression and prognostic role in prostate adenocarcinoma.

Purpose: As prostate cancer (PCa) is the second most commonly diagnosed cancer worldwide, finding novel markers for prognosis is crucial. BRCA1-associated protein 1 (BAP-1), a nuclear-localized deubiquitinating enzyme, has been reported in several human cancers. However, its prognostic role in PCa remains unknown. Herein, we assessed the prognostic and clinicopathologic significance of BAP-1 in PCa. Materials and Methods: Seventy surgical specimens from radical prostatectomy cases were examined. Two cores per case were selected for construction of tissue microarrays (TMAs). After the exclusion of two cases because of tissue sparsity, BAP-1 immunohistochemical expression was evaluated in 68 cases of formalin-fixed, paraffin-embedded TMA tissue blocks. The immunohistochemical stain was scored according to proportion of nuclear staining: negative (<10% of tumor cells) or positive (≥10% of tumor cells). Results: BAP-1 expression was negative in 30 cases (44.1%) and positive in 38 cases (55.9%). Positive BAP-1 expression was more common in pT3b disease than in pT2 (p=0.038). A high preoperative prostate-specific antigen level was correlated with BAP-1 expression (p=0.014). Age, lymphovascular invasion, perineural invasion, and grade group were not significantly correlated with BAP-1 expression. Patients with positive BAP-1 expression showed significantly shorter disease-free survival (p=0.013). Additionally, BAP-1 was an independent prognostic factor of PCa (p=0.035; hazard ratio, 9.277; 95% confidence interval, 1.165-73.892). Conclusions: Our study findings showed an association of BAP-1 expression with poor PCa prognosis and suggest a potential role for BAP-1 as a prognostic biomarker for PCa.