Abstract Introduction/Background: Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in breast cancer. The limited studies evaluating the role of FOLR1 ...in breast cancer have shown that FOLR1 protein expression is enriched in triple-negative breast cancer (TNBC) and associated with poor prognosis in all breast cancer types. Newly developed anti-FOLR1 therapy could potentially be used for patients with TNBC for whom few therapeutic options exist. We sought to evaluate FOLR1 protein expression in a cohort of patients with TNBC to determine its prevalence and prognostic value. Materials Immunohistochemistry was performed for FOLR1 in 76 cases of primary TNBC. Membranous staining in ≥5% of cells was deemed positive in a given case. Statistical analyses correlating FOLR1 protein expression with clinicopathologic parameters and clinical outcome disease-free survival (DSF) and overall survival (OS) were performed. Results 76 cases of primary TNBC were studied. Most cases were negative for FOLR1 (80.3%, 61/76). FOLR1 expression did not correlate with any clinicopathologic parameters. FOLR1 expression was significantly correlated with decreased DFS (2.61, 95% CI: 0.96-7.09, P = 0.0497 log-rank test). While FOLR1 expression trended towards decreased OS, it was not statistically significant (1.99, 95% CI: 0.62-6.36, P > 0.05 log-rank test). Conclusion We found a lower incidence of FOLR1 expression in TNBC compared to other studies; however, these patients may benefit from anti-folate therapy as other targeted therapies are not available. While no correlation between FOLR1 expression and standard clinicopathologic parameters was identified, our findings suggest that FOLR1 expression is prognostically significant in TNBC.
Summary We evaluated genomic alterations and biomarker expression in 20 florid lobular carcinomas in situ using array-based comparative genomic hybridization and immunohistochemical analysis. The ...genetic characteristics of florid lobular carcinoma in situ were compared with 20 classic lobular carcinomas in situ and 21 pleomorphic lobular carcinomas in situ (which included 8 apocrine variants), from our previously published data performed on a similar array-based comparative genomic hybridization platform. All 20 florid lobular carcinoma in situ cases were E-cadherin negative, and 92% were positive for estrogen receptor. Cyclin D1 expression correlated significantly negatively with estrogen receptor expression and was higher in cases with cyclin D1 ( CCND1 ) gene amplification. Compared with classic lobular carcinoma in situ, florid lobular carcinoma in situ displayed significantly more fraction genome alteration (mean, 0.109 versus 0.072; P = .007), fraction genome loss (mean, 0.06 versus 0.03; P = .007), numbers of breakpoints (mean, 11.55 versus 6.95; P = .002), numbers of chromosome with breakpoints (mean, 5.85 versus 3.8; P = .004), and higher numbers of amplifications (mean, 2.10 versus 0.25; P = .03). Interestingly, florid lobular carcinoma in situ had the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our study demonstrated that florid lobular carcinoma in situ shares the cytologic features, E-cadherin loss, and the lobular genetic signature of 1q gain and 16q loss found in classic lobular carcinoma in situ. However, this variant demonstrates more genomic alterations than classic lobular carcinoma in situ and shares the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our data support the conclusion that florid lobular carcinoma in situ is genetically more advanced compared with the indolent phenotype of classic lobular carcinoma in situ. This may explain the greater frequency of concurrent invasive carcinoma in florid lobular carcinoma in situ compared with classic lobular carcinoma in situ.
Summary Breast cancer patients who receive radiation therapy or develop chronic lymphedema following axillary dissection can develop secondary mammary angiosarcomas (ASs) and, additionally, atypical ...vascular lesions (AVLs) in the former group. Recently, MYC amplification by fluorescence in situ hybridization (FISH) has been identified in secondary mammary AS but not in AVL and most primary mammary AS as well as AS of other sites. We studied MYC amplification and MYC protein expression in 7 radiation-induced AVLs, 9 secondary mammary ASs, 17 primary mammary ASs, and 20 primary ASs of other sites by FISH analysis and immunohistochemistry. All 9 secondary mammary ASs showed gene amplification and protein expression, whereas neither was found in any of 7 AVLs. No MYC amplification or protein expression was identified in any of the 17 primary mammary ASs. Among primary ASs of other sites, 1 cardiac AS and 1 skin AS showed gene amplification and protein expression. The remaining 18 did not show amplification (90%), but some demonstrated protein expression (39%). We conclude that MYC amplification by FISH is present in secondary mammary AS but not in AVL. We also found MYC amplification in 1 primary skin AS and 1 primary cardiac AS. There was 100% concordance between MYC amplification and protein expression in all AVL, primary mammary AS, and secondary mammary AS, whereas only 65% concordance was found in AS of other sites. MYC protein expression in AS can be helpful in certain diagnostic scenarios in the breast but not in other sites.
Summary Adenoid cystic carcinomas (ACCs) from various anatomical sites harbor a translocation t(6;9)(q22-23;p23-24), resulting in MYB-NFIB gene fusion. This gene fusion is not well studied in mammary ...ACCs, and there are no studies examining this abnormality in solid variant of ACC with basaloid features (SBACC), a high-grade variant thought to behave more aggressively than ACCs with conventional histologic growth. Our aim was to investigate the frequency of MYB-NFIB gene fusion in mammary ACCs with a focus paid to SBACC. MYB rearrangement and MYB-NFIB fusion were assessed by fluorescence in situ hybridization and reverse-transcription polymerase chain reaction, respectively. Histologic features and the presence of MYB rearrangement were correlated with clinical outcome. MYB rearrangement was present in 7 (22.6%) of 31 mammary ACCs (5/15 33.3% ACCs with conventional growth; 2/16 12.5% SBACCs). One patient with conventional ACC developed distant metastasis, and no patients had axillary lymph node involvement by ACC (mean follow-up, 34 months; range, 12-84 months). Two patients with SBACC had axillary lymph node involvement at initial surgery, and 2 additional patients experienced disease recurrence (1 local, 1 distant; mean follow-up, 50 months; range, 9-192 months). MYB-NFIB fusion status did not correlate with clinical outcome in studied patients. We confirm that MYB - NFIB gene fusion is observed in mammary ACCs and that a subset lacks this abnormality. This study is the first to confirm the presence of MYB rearrangement in SBACC. Additional validation with long-term follow-up is needed to determine the relationship, if any, between MYB-NFIB gene fusion and clinical outcome.
Summary Classification of mammary fibroepithelial tumors (FETs) relies on assessment of mitotic activity, among other histopathologic parameters. Routine hematoxylin and eosin (H&E) mitotic counts ...can be subjective and time consuming. Difficulty may arise in identifying “true” mitoses for a variety of reasons. Phosphorylation of histone H3 protein (PHH3) is correlated with mitotic chromatin condensation. The utility of PHH3 immunohistochemical staining to identify mitoses has been demonstrated in multiple organ systems. In this study, we examined the utility of PHH3 in assessing mitotic activity in FETs and compared PHH3- with H&E-determined mitotic counts. PHH3-stained mitoses were readily identifiable at ×10 magnification and allowed for rapid identification of mitotic “hot spots.” Median mitotic counts/10 high-power fields for fibroadenoma, benign phyllodes tumor, borderline phyllodes tumor (BlnPT), and malignant phyllodes tumor (MPT) were 0, 0.5, 4.25, and 9, respectively on H&E, and 0, 0.75, 4.5, and 8, respectively for PHH3. Among all FETs, there was a strong positive correlation between H&E- and PHH3-determined mitotic counts ( r = 0.91, P < .001). Using PHH3, 2 cases would be reclassified, both from BlnPT to MPT. PHH3-determined counts correlated with H&E-determined counts in FETs. Using PHH3, a small number of cases were reclassified from BlnPT to MPT, for which treatment is similar. Although H&E-determined counts remain the criterion standard for assessing mitotic activity in FETs, PHH3 may be a useful adjunctive tool in some cases and is helpful in identifying mitotic hot spots.
Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a family of CD34-positive tumors with ...similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates distinct smooth muscle differentiation which can be confused with other smooth muscle tumors of the breast, itself constituting a rarified morphological subgroup. We aimed to characterize 4 cases of the leiomyomatous variant of myofibroblastoma arising in the breast by clinicopathological, immunohistochemical, and molecular means. All 4 examples arose in women aged 41–62 years (median, 46.5 years). Tumors ranged in size from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were characterized by bundles of smooth muscle cells with elongated cigar-shaped nuclei and eosinophilic cytoplasm. All four tumors showed diffuse positive staining with desmin, caldesmon, smooth muscle actin (SMA), estrogen receptor (ER), and Bcl-2. CD34 staining was diffusely positive in two cases, weak and patchy in one case, and was negative in one case. Two of four (50%) tumors showed deletion of RB1 by fluorescence in situ hybridization (FISH). Loss of Rb staining was seen in one tumor with RB1 deletion by FISH, while intact Rb staining was observed in one non-deleted case studied. In conclusion, this rare variant of myofibroblastoma is a distinct subgroup of tumors among an already uncommon category of (smooth muscle) breast tumors. Some reported examples of “parenchymal leiomyoma” may represent the leiomyomatous variant of myofibroblastoma.
A case of primary breast angiosarcoma Dashevsky, Brittany Zadek, MD, DPhil; Charnoff-Katz, Karin, MD; Shin, Sandra J, MD ...
Radiology case reports,
2013, Letnik:
8, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract Angiosarcoma of the breast is a rare malignancy that may be easily misdiagnosed. Of the two forms, the more common form presents in patients (typically postmenopausal0 with a history of ...breast cancer, secondary to irradiation or chronic lymphedema. In contrast, the rarer form, primary angiosarcoma, arises sporadically in premenopausal women who present with palpable masses. Primary angiosarcoma accounts for 1 in 2,500 cases (0.04%) of breast cancer ( 1 ). The described patient presented with primary breast angiosarcoma. Ultrasound, mammography, and magnetic resonance imaging findings are presented.
In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum
Negarnaviricota
was amended and emended. The phylum was ...expanded by two new families (bunyaviral
Discoviridae
and
Tulasviridae
), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of
Negarnaviricota
as now accepted by the ICTV.
Highlights ► Global Vaccine Safety Blueprint Strategy developed in 2011. ► Strategy is based on landscape analysis of vaccine safety stakeholders and systems. ► Strategy aims at minimal and enhanced ...country capacity and global support network. ► Global Vaccine Safety Initiative launched 2012, supports implementation of Strategy. ► Decade of Vaccines is opportunity to raise awareness for Blueprint implementation.