Maspin expression is frequent and correlates with basal markers in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Maspin is a unique member of the serine protease inhibitor superfamily and its expression is found in myoepithelial cells of normal mammary glands; therefore, it has been considered to be a myoepithelial marker. We previously reported that maspin was frequently expressed in biologically aggressive breast cancers. In turn, triple-negative (TN) breast cancer is a subtype of tumor with aggressive clinical behavior and shows frequent expression of basal markers. We hypothesized that maspin expression may be frequent and correlate with basal rather than myoepithelial markers in TN breast cancer.</p> <p>Methods</p> <p>Paraffin-embedded 135 TN invasive ductal carcinoma tissue samples were immunohistochemically investigated using the Dako Envision+ kit and primary antibodies for maspin, basal (CK5/6, EGFR, CK14) and myoepithelial markers (p63, CD10). The correlation between maspin expression and relapse-free survival (RFS) was investigated by the log-rank test.</p> <p>Results</p> <p>The positive rate for maspin was 85.9% and significantly correlated with younger age (<it>P </it>= 0.0015), higher histological grade (<it>P </it>= 0.0013), CK5/6 positivity (<it>P </it>< 0.0001), CK14 positivity (<it>P </it>= 0.0034) and the basal-like subtype defined by CK5/6, EGFR and CK14 positivity (<it>P </it>= 0.013). The positive rates for CK5/6, EGFR, CK14, CD10 and p63 were 59.2%, 48.9%, 34.1%, 17.8% and 12.6%, respectively. There was no significant correlation between maspin expression and RFS.</p> <p>Conclusions</p> <p>The positive rate for maspin is the highest among known basal and myoepithelial markers, and strongly correlates with basal markers in TN breast cancer. These results suggested that maspin could be a candidate for a therapeutic target for TN breast cancer.</p

Mucocele-like lesions of the breast: a long-term follow-up study

<p>Abstract</p> <p>Background</p> <p>Mucocele-like lesions (MLL) of the breast were originally described as benign lesions composed of multiple cysts lined by uniform flat to cuboidal epithelium with extravasated mucin, but subsequent reports described the coexistence of columnar cell lesions (CCL), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). Several reports have investigated whether core biopsy can diagnose MLL reliably; however, there is only one report with a long-term follow-up after excision of MLL. We report here 15 surgically excised MLL with a long-term follow-up.</p> <p>Findings</p> <p>Fifteen lesions diagnosed as MLL from 13 patients who had undergone excisional biopsy between January 2001 and December 2006 were retrieved and followed-up for 24-99 months (median 63.8). Two lesions were accompanied with CCL, 5 with ADH and 3 with low grade DCIS. Four lesions (2 ADH, 2 DCIS) were additionally resected and their histology revealed 2 ADH, one DCIS and one MLL with CCL. Of 4 lesions (3 ADH, one DCIS) without additional resection, one lesion (ADH) relapsed accompanied with DCIS at 37 months after excision.</p> <p>Conclusions</p> <p>MLL were frequently accompanied with CCL, ADH or low grade DCIS. Complete resection may be recommended in case of MLL with ADH or DCIS because of intralesional heterogeneity and the probabilities of relapse.</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570