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Introduction: HER2‐low breast cancer is a gradually recognized and unexplored group of diseases. We aimed to investigate the clinical and prognosis features and to identify the role of stromal tumor‐infiltrating lymphocytes (sTILs) in this population. Methods: Consecutive primary breast cancer patients treated between January 2009 to June 2013 were retrospectively reviewed. HER2‐low was defined as immunohistochemistry (IHC) 1+, or 2+ and fluorescence in situ hybridization (FISH) negative. sTILs were scored following the international guidelines. Clinicopathologic features and survival were compared according to HER2 and sTILs category. Results: A total of 973 breast cancer patients were enrolled, including 615 (63.2%) HER2‐low patients. HER2‐low patients shared more similarity with HER2‐0 cases in clinicopathological features. sTILs in HER2‐Low patients was comparable to HER2‐0 patients (p = 0.064), both significantly lower than HER2‐positive ones (p < 0.001). Meanwhile, tumors with sTILs ≥50% accounted for the least proportion of HER2‐low cases (p < 0.001). HER2 status had no significant influence on recurrence‐free survival (RFS, p = 0.901) in the whole population. However, in the estrogen receptor (ER)‐negative subgroup, HER2‐low was related to worse RFS (p = 0.009) and OS (p = 0.001) compared with HER2‐positive ones. sTILs increment was an independent favorable prognostic factor in the whole (OS, p = 0.003; RFS, p = 0.005) and HER2‐low population (OS, p = 0.007; RFS, p = 0.009) after adjusted to clinicopathological parameters. Conclusions: HER2‐low patients shared similar clinicopathological features with HER2‐0 rather than HER2‐positive cases and had relatively low sTILs. ER‐negative/HER2‐low patients had significantly inferior survival. sTILs increment was independently associated with favorable survival in the HER2‐low group, suggesting a potential benefit from a novel treatment strategy. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3α and EP3β, but not EP3γ, isoforms diminished hypoxia-induced TGF-β1 activation. Expression of either EP3α or EP3β in EP3-deficient PASMCs restored TGF-β1 activation in response to hypoxia. EP3α/β activation in PASMCs increased RhoA-dependent membrane type 1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro-MMP-2 and promoting TGF-β1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary hypertension., Introduction Pulmonary arterial hypertension (PAH), a rare but often fatal disease characterized by an average pulmonary arterial (PA) pressure of greater than 25 mmHg, contributes to unacceptably high morbidity and [...]

Simple Summary: Novel anti-HER2 antibody–drug conjugates showed convincing efficacy in HER2-Low breast cancer patients. We aimed to investigate the accuracy of core needle biopsy (CNB) in diagnosing HER2-Low status. We found a low concordance rate of HER2-Low status between CNB and surgical excision specimen (SES) samples in early-stage HER2-Negative patients. In tumors identified as HER2-0 by CNB, 50.3% expressed HER2 at any level at SES samples. Our research confirmed the necessity of retesting HER2-Low status in SES samples to guide precise anti-HER2 ADCs therapy. Background: HER2-Low status is found in approximately half of breast cancer patients and shows potential benefits from novel antibody–drug conjugates (ADCs). Data on the accuracy of HER2-Low status between core needle biopsy (CNB) and surgical excision specimen (SES) samples are lacking. We aimed to investigate the accuracy of HER2-Low status diagnosis between CNB and SES samples. Methods: Consecutive early-stage breast cancer patients who underwent surgery from January 2009 to March 2022 with paired CNB and SES samples were retrospectively reviewed. HER2-Low was defined as IHC 1+ or IHC2+ and FISH-negative. Concordance rates were analyzed by the Kappa test. Further clinicopathological characteristics were compared among different HER2 status and their changes. Results: A total of 5610 patients were included, of whom 3209 (57.2%) and 3320 (59.2%) had HER2-Low status in CNB and SES samples, respectively. The concordance rate of HER2 status in the whole population was 82.37% (Kappa = 0.684, p < 0.001), and was 76.87% in the HER2-Negative patients (Kappa = 0.372, p < 0.001). Among 1066 HER2-0 cases by CNB, 530 patients were classified as HER2-Low tumors. On the contrary, in 3209 patients with HER2-Low tumor by CNB, 387 were scored as HER2-0 on the SES samples. ER-negative or Ki67 high expression tumor by CNB had a high concordance rate of HER2-Low status. Conclusions: A relatively low concordance rate was found when evaluating HER2-Low status between CNB and SES samples in HER2-Negative breast cancer patients, indicating the necessity of retesting HER2 low status at surgery, which may guide further therapy in the era of anti-HER2 ADCs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the predictive and prognostic value of tumor‐infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Patients and methods: Consecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease‐free survival (DFS), and overall survival. Results: A total of 461 patients were included. The mean pre‐NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p < 0.0001). The multivariate analysis demonstrated that a high pre‐NAC TIL level was an independent risk factor for a higher pCR (odds ratio = 3.92, 95% CI = 2.23–6.90, p < 0.001). Patients with high pre‐NAC TIL levels had a better 5‐year DFS than those with low pre‐NAC TIL levels (84.5% vs. 68.9%, HR = 0.50, 95% CI = 0.31–0.81, p = 0.005). The multivariate analysis showed that pre‐NAC TIL (HR = 0.48; 95% CI = 0.29–0.81, p = 0.006) but not post‐NAC TIL (HR = 0.89, 95% CI = 0.50–1.59, p = 0.699) was significantly associated with DFS among patients without pCR. Furthermore, patients with low pre‐ and post‐NAC TIL levels had a worse 5‐year DFS than those with high pre‐NAC TIL levels (HR = 2.09, 95% CI = 1.23–3.56, p = 0.007). Conclusions: Pre‐NAC TIL level can predict pCR and DFS in patients with breast cancer receiving NAC. For patients without pCR, pre‐NAC TIL, and TIL category change, but not post‐NAC TIL, were significantly associated with DFS. [ABSTRACT FROM AUTHOR]

Background: It remains uncertain whether the 21-gene recurrence score (RS) of a primary tumor has selective prognostic value for locoregional recurrence (LRR) or distant metastasis (DM). The current study aimed to compare the distribution and single-gene expression on the RS panel in breast cancer patients with LRR versus DM. Methods: Consecutive early breast cancer patients who had been operated on at the Comprehensive Breast Health Center, Ruijin Hospital from January 2009 to December 2016 were retrospectively reviewed. Patients were divided into LRR, DM, and no-recurrence groups according to the first reported recurrent event. Comparison and subgroup analysis of 21-gene RS, RS category, and single-gene expression on the RS panel were conducted among patients with different recurrence status. Results: A total of 1,287 patients were included, with median follow-up of 61.5 months, and 27, 47, and 1,213 patients were classified as LRR, DM, and no recurrence groups, respectively. RS was significantly diversely distributed among the three groups (P< 0.001). No-recurrence patients (median 22) presented much lower RS than LRR (median 39, P< 0.001) and DM (median 30, P< 0.001) patients. LRR patients had lower PR (P< 0.001), BCL2 (P=0.010), and CEGP1 (P< 0.001) expression, and DM patients had higher STMY3 (P=0.019) expression than no-recurrence patients. Moreover, CEGP1 expression was significantly lower in the LRR group than the DM one (P=0.028). Conclusion: RS was differently distributed between recurrent and nonrecurrent patients. PR, BCL2, CEGP1, and STMY 3 expression was associated with LRR and DM, while CEGP1 was lower in the LRR group than DM patients, warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease of the exocrine glands characterized by specific pathological features. Previous studies have pointed out that salivary glands from pSS patients express a unique profile of cytokines, adhesion molecules, and chemokines compared to those from healthy controls. However, there is limited evidence supporting the utility of individual markers for different stages of pSS. This study aimed to explore potential biomarkers associated with pSS disease progression and analyze the associations between key genes and immune cells. Methods: We combined our own RNA sequencing data with pSS datasets from the NCBI Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) via bioinformatics analysis. Salivary gland biopsies were collected from 14 pSS patients, 6 non-pSS patients, and 6 controls. Histochemical staining and scanning electron micrographs (SEM) were performed to macroscopically and microscopically characterize morphological features of labial salivary glands in different disease stages. Then, we performed quantitative PCR to validate hub genes. Finally, we analyzed correlations between selected hub genes and immune cells using the CIBERSORT algorithm. Results: We identified twenty-eight DEGs that were upregulated in pSS patients compared to healthy controls. These were mainly involved in immune-related pathways and infection-related pathways. According to the morphological features of minor salivary glands, severe interlobular and periductal lymphocytic infiltrates, acinar atrophy and collagen in the interstitium, nuclear shrinkage, and microscopic organelle swelling were observed with pSS disease progression. Hub genes based on above twenty-eight DEGs, including MS4A1, CD19, TCL1A, CCL19, CXCL9, CD3G, and CD3D, were selected as potential biomarkers and verified by RT-PCR. Expression of these genes was correlated with T follicular helper cells, memory B cells and M1 macrophages. Conclusion: Using transcriptome sequencing and bioinformatics analysis combined with our clinical data, we identified seven key genes that have potential value for evaluating pSS severity. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) patients with T1N0 tumors have relatively favorable clinical outcomes. However, it remains unclear whether molecular subtypes can aide in prognostic prediction for such small, nodal-negative BC cases and guide decision-making about escalating or de-escalating treatments. Patients and Methods: T1N0 BC patients diagnosed between 2009 and 2017 were included and classified into three subgroups according to receptor status: 1) hormonal receptor (HR)+/human epidermal growth factor receptor-2 (HER2)−; 2) HER2+; and 3) triple negative (TN) (HR−/HER2−). Patients' characteristics and relapse events were reviewed. Kaplan–Meier analysis and Cox regression were used to assess the iDFS and BCSS. The effects of risk factors and adjuvant treatment benefits were evaluated by calculating hazard ratios (HRs) for invasive disease-free survival (iDFS) and breast cancer-specific survival (BCSS) with Cox proportional hazards models. Results: In total, 2,168 patients (1,435 HR+/HER2−, 427 HER2+, 306 TN) were enrolled. The 5-year iDFS rates were 93.6, 92.7, and 90.6% for HR+/HER2−, HER2+, and TN patients, respectively (P = 0.039). Multivariate analysis demonstrated that molecular subtype (P = 0.043), but not tumor size (P = 0.805), was independently associated with iDFS in T1N0 BC. TN patients [HRs = 1.77, 95% confidence interval (CI) = 1.11–2.84, P = 0.018] had a higher recurrence risk than HR+/HER2− patients. Adjuvant chemotherapy benefit was not demonstrated in all T1N0 patients but interacted with molecular subtype status. TN (adjusted HRs = 2.31, 95% CI = 0.68–7.54) and HER2+ (adjusted HRs = 2.26, 95% CI = 0.95–5.63) patients receiving chemotherapy had superior iDFS rates. Regarding BCSS, molecular subtype tended to be related to outcome (P = 0.053) and associated with chemotherapy benefit (P = 0.005). Conclusion: Molecular subtype was more associated with disease outcome and chemotherapy benefit than tumor size in T1N0 BC patients, indicating that it may guide possible clinical de-escalating therapy in T1N0 BC. [ABSTRACT FROM AUTHOR]

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents—findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Pseudogenes exert potential functions in tumorigenicity and tumour process in human beings. In our previous research on oncogene AKR1B10 in hepatocellular carcinoma (HCC), its pseudogene, AKR1B10P1, was preliminarily noticed being anomalistic transcribed, whereas whether AKR1B10P1 plays any specific function in HCC is poorly understood. By using shRNA transfection and lentiviral infection, we regulated the expression of ARK1B10P1 transcript and the relative targets in two ways. As we discovered, pathological transcription of AKR1B10P1 in HCC cells significantly promotes cell growth and motility either in vitro or in vivo. AKR1B10P1 was correlated with relatively dismal features of HCC. The epithelial‐mesenchymal transition (EMT) was enhanced by up‐regulating AKR1B10P1. And, a potential sequence of AKR1B10P1 transcript was discovered directly interacting with miR‐138. SOX4, a pivotal promotor of EMT, was validated as the down‐streaming target of miR‐138. Mechanistically, degradation of SOX4 mRNA induced by miR‐138 was effectively abrogated by AKR1B10P1. In conclusion, pseudogene AKR1B10P1 exerts stabilizing effect on SOX4 in HCC, associated EMT process, by directly sponging miR‐138, which post‐transcriptionally modulates SOX4's regulating gene. [ABSTRACT FROM AUTHOR]

Background: Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). Methods: Patients with node-negative ER+/HER2- breast cancer and complete data of gene expressions in a 21-gene panel were retrospectively retrieved from Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB). The F2P Score was established based on the clinical and genomic variables associated with the first-2-year relapse after shrinkage correction and validated using the bootstrap resampling method. Model performance was quantified by Harrell's concordance-index (C-index) and Bayesian information criteria (BIC). Results: The F2P Score was established by integrating the clinical (age and tumor size) and genomic (ESR1, PGR, BCL2, CD68, GSTM1 , and BAG1) variables with a C-index of 0.71 and BIC of 397.46. Bootstrap C-index was 0.72 (95% CI, 0.62–0.81) and BIC was 396.75 (95% CI, 252.37–541.13). A higher score indicated an increased likelihood of a first-2-year relapse, when used as continuous (HR, 2.94; 95% CI, 1.87–4.61) or categorical (HR, 3.68; 95% CI, 1.70–8.00) predictors in multivariate analysis. Both continuous and categorical F2P Score also remained prognostic for overall survival and other endpoints. No significant interaction was observed between the F2P Score and treatment subgroups. Additionally, the F2P Score outperformed the IHC4, clinical treatment score and 21-gene test in predicting first-2-year relapse. Conclusion: The F2P Score reported herein, integrating the clinicopathological and genomic variables, may inform prognosis and endocrine responsiveness. After the benefits and risks have been considered, treatment escalation may be an alternative strategy for patients with a higher score. [ABSTRACT FROM AUTHOR]

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown. Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups. Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS. Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation. [ABSTRACT FROM AUTHOR]

Objectives: To explore the characteristics of breast ductal carcinoma in situ (DCIS) on real‐time grayscale contrast‐enhanced ultrasound (CEUS) imaging and the diagnostic value of CEUS in DCIS. Methods: A total of 127 histopathologically confirmed DCIS lesions and 124 fibroadenomas (FAs; controls) were subjected to conventional ultrasound and CEUS. Next, the CEUS findings of DCIS and FA lesions, including morphologic features and quantitative parameters, were analyzed. Results: Binary logistic regression was used to identify the independent risk factors from DCIS and FA lesions detected by CEUS. Contrast‐enhanced ultrasound revealed significant differences between DCIS and FA. The wash‐in time, enhancement mode, enhancement intensity, blood perfusion defects, peripheral high enhancement, enhancement scope, intratumoral vessels and their courses and dilatation degree, and penetrating vessels on CEUS were identified as features correlated with DCIS (P <.05). Moreover, a multivariate logistic regression analysis was developed, and the area under receiver operating characteristic curve of each index was generated, including the wash‐in time, enhancement intensity, blood perfusion defects, enhancement scope, penetrating vessels, arrival time, and peak intensity (P <.05; area under the curve, >0.6). Conclusions: The contrast‐enhancement patterns and DCIS parameters appeared different from FA lesions, thus suggesting that CEUS can be very useful in distinguishing DCIS from FA lesions. [ABSTRACT FROM AUTHOR]

Luminal subtypes and the 21-gene recurrence score (RS) are important factors in the decision-making process for adjuvant chemotherapy in patients with hormonal receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, their effect on adjuvant chemotherapy decisions in the real world has not been thoroughly investigated, particularly for patients of the luminal A-like subtype with a high RS or the luminal B-like subtype with a low RS. The present study, a total of 772 HR+/HER2− patients who underwent 21-gene testing, were included in a retrospective analysis. The impact of clinicopathological factors and the 21-gene RS on chemotherapy recommendation was analyzed in the whole population and for patients of different luminal subgroups. The results revealed that chemotherapy was highly recommended for patients of younger age, with larger tumor size, node involvement, higher grade, luminal B-like subtype and higher RS. A high RS was identified to be the most important impact factor for chemotherapy recommendation among all patients [odds ratio (OR), 62.54; 95% CI, 25.58–152.92], the luminal A-like group (OR, 435.05; 95% CI, 29.90–6331.06) and the luminal B-like group (OR, 57.20; 95% CI, 22.42–145.96). For patients of the luminal A-like subtype with a high RS or patients of the luminal B-like subtype with low RS, the 21-gene RS was demonstrated to be the most important independent factor for chemotherapy recommendation, with an adjusted OR of 134.52 (95% CI, 10.39–1741.89). In conclusion, luminal subtypes and the 21-gene RS were found to be associated with chemotherapy recommendation for HR+/HER2− patients. For patients with a discordant luminal subtype and 21-gene RS risk, the 21-gene RS score was found to be the most important factor that influences chemotherapy decision, which warrants further clinical evaluation. [ABSTRACT FROM AUTHOR]

SLC7A5, who is also named LAT-1, has been validated as a promoter regulated by miRNA-126 in our previous research for gastric cancer cells. However, the mechanisms driving SLC7A5 to affect the bio-function of gastric cancer cells are unclear, remaining us lots of to elucidate. The aim of this study is to investigate the regulating effect of CRKL, one of the critical genes involving with gastric cancer progression, on SLC7A5 expression. By studying the gastric cancer cell lines and clinical pathological specimens, we found that the expression of SLC7A5 was significantly correlated to CRKL. By depleting CRKL in gastric cancer SGC-7901 cells, the SLC7A5 expression was impaired, and the invasion and migration of SGC-7901 cells were suppressed. Ectopic expression of SLC7A5 could drastically rescue the phenotypes induced by CRKL depletion in this study. Accordingly, we conclude that SLC7A5 functions as a promoter in gastric cancer metastasis, and CRKL could be one of its regulators modulating the expression of SLC7A5 and consequentially affect the metastatic feature of SGC-7901 cells. The findings in this study indicate a regulation relationship between CRKL and SLC7A5, and provide useful evidence for gastric cancer therapeutic strategies. [ABSTRACT FROM AUTHOR]

Inflammation and tumor immune microenviroment are critical factors for prognosis in numerous cancers. The aim of this study was to determine the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) in breast cancer. We performed a retrospective analysis of 487 patients diagnosed with primary breast cancer at Shanghai Ruijin hospital from January 2009 to December 2010. Hematological parameters before surgery, clinicopathological data, and survival status were obtained. Survival analysis was used to evaluate the prognostic value of NLR. The optimal cutoff value was determined as 1.93 for NLR and the median follow-up time was 55.0 months. On univariate analysis, patients with high NLR (>1.93) had worse 5-year disease-free survival (DFS) compared to those with low NLR (77.9 vs 88.0 %, p = 0.002). Regarding overall survival, there was no significant difference between patients with high NLR and low NLR, with 5-year overall survival of 90.8 and 91.7 % ( p = 0.707). In triple-negative breast cancer, patients with high NLR was associated with worse 5-year DFS compared with patients with low NLR (63.4 vs 84.9 %, p = 0.040). Mutivariate analysis revealed that NLR was an independent prognostic factor for DFS in breast cancer (HR = 1.867, 95 % confidence interval; (95%CI) = 1.155-3.017, p = 0.011). Preoperative NLR is an independent predictor of DFS in breast cancer patients, especially in triple-negative subtype. Further studies are required to validate the prognostic value of NLR before clinical application. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to evaluate the imaging features of breast lymphoma using magnetic resonance imaging (MRI). Methods: This retrospective study consisted of seven patients with pathologically confirmed breast lymphoma. The breast lymphomas were primary in six patients and secondary in one patient. All patients underwent preoperative dynamic contrast-enhanced MRI and one underwent additional diffusion-weighted imaging (DWI) with a b value of 600 s/mm2. Morphologic characteristics, enhancement features, and apparent diffusion coefficient (ADC) values were reviewed. Results: On MRI, three patients presented with a single mass, one with two masses, two with multiple masses, and one with a single mass and a contralateral focal enhancement. The MRI features of the eight biopsied masses in seven patients were analyzed. On MRI, the margins were irregular in six masses (75%) and spiculated in two (25%). Seven masses (87.5%) displayed homogeneous internal enhancement, while one (12.5%) showed rim enhancement. Seven masses (87.5%) showed a washout pattern and one (12.5%) showed a plateau pattern. The penetrating vessel sign was found in two masses (25%). One patient with two masses underwent DWI. Both masses showed hyperintense signal on DWI with ADC values of 0.867×10-3 mm2/s and 0.732×10-3 mm2/s, respectively. Conclusion: Breast lymphoma commonly presents as a homogeneously enhancing mass with irregular margins and displays a washout curve pattern on dynamic MRI. A low ADC value may also indicate a possible diagnosis of breast lymphoma. [ABSTRACT FROM AUTHOR]

Background: To investigate the accuracy of core needle biopsy (CNB) in evaluating breast cancer estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 status and to identify factors which might be associated with Ki67 value change after CNB.Methods: A retrospective study was carried out on 276 patients with paired CNB and surgically removed samples (SRS). Clinico-pathological factors as well as the surgery time interval (STI) between CNB and surgery were analyzed to determine whether there were factors associated with Ki67 value change after CNB. Five tumor subtypes were classified as follows: Luminal A, Luminal B-HER2-, Luminal B-HER2+, Triple Negative (TN), and HER2+. Ki67 value change was calculated as SRS minus CNB.Results: Mean STI after CNB was 4.5 (1-37) days. Good agreement was achieved for ER, PR, and HER2 evaluation between CNB and SRS. However, Ki67 expression level was significantly higher in SRS compared with CNB samples: 29.1 % vs. 26.2 % (P < 0.001). Both univariate and multivariate analysis demonstrated that STI and molecular subtype were associated with a Ki67 change after CNB. Luminal A tumors experienced more Ki67 elevation than Luminal B-HER2- diseases (6.2 % vs -0.1 %, P = 0.014). Patients with longer STI after CNB had a higher Ki67 increase: -1.1 % within 1-2 days, 2.1 % with 3-4 days, and 5.6 % more than 4 days, respectively (P = 0.007). For TN and HER2+ tumors, the Ki67 change was apt to be 0 with STI ≤ 4 days, while a >7 % Ki67 increase was noticed in patients with STI ≥ 5 days.Conclusion: CNB was accurate in evaluating ER, PR, HER2, and molecular subtype status. Ki67 value significantly increased after CNB, which was associated with STI and molecular subtype. Further translational research needs to consider Ki67 changes following CNB among different breast cancer molecular subtypes. [ABSTRACT FROM AUTHOR]

In non-pSS (Grade II), the duct structure of normal glands is clear, and ductal epithelial cells have full nuclei and are connected with myoepithelial cells by desmosomes. Primary Sjogren's syndrome (pSS), bioinformatics analysis, severity, transcriptome sequencing, potential biomarkers Keywords: primary Sjogren's syndrome (pSS); transcriptome sequencing; potential biomarkers; bioinformatics analysis; severity EN primary Sjogren's syndrome (pSS) transcriptome sequencing potential biomarkers bioinformatics analysis severity 1 2 2 10/01/21 20210929 NES 210929 In the original article, there was a mistake in the legends for B Figures 7 b , B Figure 8 b as published. [Extracted from the article]

Background: The chromodomain helicase/adenosine triphosphatase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21. CHD1L protein over-expression in primary hepatocellular carcinoma is correlated with enhanced apoptosis inhibition, reduced chemosensitivity and shortened patient survival. However, CHD1L protein status or mRNA expression in breast cancer and its clinical significance remain obscure. Material and Methods: In this study, immunohistochemical staining for CHD1L expression was performed on tissue microarrays containing 179 primary invasive breast cancers and 65 matched normal breast tissue specimens. Clinico-pathological features were collected and compared between different CHD1L statuses. Kaplan-Meier curves were applied to estimate disease-free survival (DFS) and overall survival (OS). Cox regression was used to identify independent prognostic factors. Also, quantitative real-time polymerase chain reaction (QRT-PCR) was employed to evaluate the mRNA level expression of CHD1L in six breast cancer cell lines. Results: Presence of CHD1L over-expression was observed in 87 of the 179 patients (48.6%), which associated with a younger age (P = 0.011), higher grade (P = 0.004), higher Ki-67 index (P = 0.018) and HER2 over-expression/amplification (P = 0.037). After a median follow-up of 55 months, patients with presence of CHD1L over-expression had significantly poorer DFS (82.6% Vs 76.3%, P = 0.035), but not OS (87.0% Vs 94.9%, P = 0.439). In multivariate analysis, CHD1L status (HR = 2.169, [95%CI, 1.029–4.573], P = 0.042), triple negative subtype (HR = 2.809, [95%CI 1.086–7.264], P = 0.033) and HER2 positive subtype (HR = 5.221, [95%CI 1.788–15.240], P = 0.002) were identified as independent prognostic factors for DFS. In vitro study indicated that relative mRNA expression level of CHD1L was higher in breast cancer cell lines, especially in MDA-MB-231 and LM2-4175, when compared to normal breast epithelial cell line. Conclusions: Presence of CHD1L over-expression is probably associated with aggressive tumor biology in breast cancer. CHD1L status might be a novel prognostic biomarker for patients with breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making. Patients and Methods: A total 398 patients with luminal B/HER2-negative breast cancer were included. Kaplan-Meier curves were applied to estimate disease-free survival and Cox regression to identify prognostic factors. Results: Progesterone receptor (PR) negative expression was associated with higher tumor grade (p<.001) and higher Ki-67 index (p = .010). PR-negative patients received more chemotherapy than the PR-positive group (p = .009). After a median follow-up of 28 months, 17 patients (4.3%) had early relapses and 8 patients (2.0%) died of breast cancer. The 2-year disease-free survival was 97.7% in the PR-positive and 90.4% in the PR-negative groups (Log-rank p = .002). Also, patients with a high Ki-67 index (defined as >30%) had a reduced disease-free survival (DFS) when compared with low Ki-67 index group (≤30%) (98.0% vs 92.4%, respectively, Log-rank p = .013). In multivariate analysis, PR negativity was significantly associated with a reduced DFS (HR = 3.91, 95% CI 1.29–11.88, p = .016). Conclusion: In this study, PR negativity was a prognostic factor for early relapse in luminal B/HER2-negative breast cancer, while a high Ki-67 index suggested a higher risk of early relapse. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the capacity of magnetic resonance imaging (MRI) to distinguish breast cancer from inflammatory breast diseases manifesting as a rim-enhanced mass with central cystic changes. Materials and Methods: Forty cases of breast cancer and 52 of inflammatory breast diseases showing a rim-enhanced mass with central cystic changes were retrospectively reviewed. All cases underwent dynamic contrast-enhanced MRI and 31 of them underwent diffusion-weighted imaging (DWI). Morphological features, dynamic parameters and apparent diffusion coefficient (ADC) values were comparatively analyzed using univariate analysis and binary logistic regression analysis. Results: Breast cancer had a significantly thicker wall than the inflammatory breast diseases (P<0.001) while internal enhancing septa were more common in inflammatory breast diseases (P = 0.003). On DWI, 86.7% of breast cancers demonstrate a peripheral hyperintensity whereas 93.8% of inflammatory breast diseases had a central hyperintensity (P<0.001). Compared to the inflammatory breast diseases, breast cancers had a lower ADC value for the wall (1.09×10−3 mm2/s vs 1.42×10−3 mm2/s, P<0.001) and a higher ADC value for the central part (1.94×10−3 mm2/s vs 1.05×10−3 mm2/s, P<0.001). Conclusions: Both breast cancer and inflammatory breast diseases could present as a rim-enhanced mass with central cystic changes on MRI. Integrated analysis of the MR findings can allow for an accurate differential diagnosis. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/ncomms15533 [ABSTRACT FROM AUTHOR]

The genomic alterations for benign thyroid nodule, especially adenomatoid nodule, one of the most common types of hyperplasia lesion, are ill-studied. Here, we show whole-exome sequencing and/or transcriptome sequencing data on adenomatoid nodules with or without coincidental papillary thyroid carcinoma (PTC). Somatic mutation of BRAF (22/32) is only detected in PTC, while mutations in SPOP (4/38), ZNF148 (6/38) and EZH1 (3/38) are found enriched in adenomatoid nodule. In an expanded cohort of adenomatoid nodule (n=259) mutually exclusive SPOPP94R, EZH1Q571R and ZNF148 mutations are identified in 24.3% of them. Adenomatoid nodules show very few overlapped mutations and distinct gene expression patterns with their coincidental PTC. Phylogenetic tree analysis uncovers that PTCs evolved independently from their matched benign nodules. Our findings reveal that benign nodules possess a unique molecular signature that differs from PTC and provide genomic evidence for the conventional belief that PTC and benign nodules have independent origin. [ABSTRACT FROM AUTHOR]