Harold C. Sullivan

GATA-3 expression in male and female breast cancers: comparison of clinicopathologic parameters and prognostic relevance

Expression of GATA-3 in female breast cancers has been linked to estrogen receptor (ER) expression and, in turn, to improved outcomes. However, GATA-3 has not been studied in male breast cancers. Nineteen male breast carcinomas (average age: 63 years) and 164 female breast carcinomas (average age: 57 years) were immunostained for GATA-3. Results were compared to age, tumor size, tumor grade, lymph node status, distant metastases, survival, and positivity for ER, progesterone receptor (PR), and HER2/neu. Six of 19 (31.6%) male and 135 of 164 (82.3%) female breast carcinomas were GATA-3 positive (P < .001). In women, 82.1% of GATA-3-positive cancers were grade 1 or 2, whereas 75.9% of GATA-3-negative cancers were grade 3 (P < .001); no such significant correlation was seen in men. Unlike female cancers, male cancers showed no correlation between GATA-3 positivity and ER positivity, PR positivity, or distant metastases. Nodal metastasis and HER2 status were not linked to GATA-3 in either sex. Seventeen (89.5%) men were alive at follow-up (average: 61 months); only 1 died of disease. Most women (159/164, 97.0%) were also alive at follow-up (average: 41 months), with a higher proportion of GATA-3-negative women dead than GATA-3-positive women (3/29 [10.3%] vs. 2/135 [1.5%], P = .039). GATA-3 is expressed less often in male than female breast cancers. Male cancers show no correlation between GATA-3 positivity and ER/PR positivity or distant metastases, unlike female cancers. There appears to be no link between GATA-3 positivity and survival in men, whereas in women, GATA-3-positive tumors are typically lower grade with a better prognosis.

The utility of ERG, CD31 and CD34 in the cytological diagnosis of angiosarcoma: an analysis of 25 cases

Aims Erythroblast transformation specific related gene (ERG), a proto-oncogene member of the erythroblast transformation specific transcription factor family, is a sensitive marker of endothelial differentiation and is expressed in vascular tumours, including angiosarcomas (AS). Immunohistochemistry is necessary for the diagnosis of AS in fine needle aspirates where low cellularity and lack of preserved tissue architecture impedes diagnosis. The aim of this study was to assess the utility of an ERG-enriched immunohistochemistry panel in the cytological diagnosis of AS. Methods 25 AS diagnosed on fine needle aspirates were stained for ERG, CD31, CD34, and AE1/AE3. Staining intensity and percentage tumour cell positivity were evaluated. Spearman’s correlation was assessed for significant correlations between antibodies. Results Sensitivities for ERG, CD31, CD34 and AE1/AE3 were 100%, 100%, 60% and 21%, respectively. Spearman’s analysis revealed that ERG and CD31 staining correlated significantly; there was no significant correlation between CD31 and CD34 staining. Conclusions With equal sensitivity to, and strong correlation with CD31, ERG staining is highly suitable for the cytological diagnosis of AS. ERG and CD31 are more sensitive vascular markers than CD34. ERG, a nuclear stain, complements the cytoplasmic/membranous staining of CD31. Used in conjunction with CD31, ERG can corroborate the diagnosis of AS.

Daratumumab (anti-CD38) induces loss of CD38 on red blood cells

To the editor: The recently approved anti-CD38 monoclonal antibody daratumumab (DARA) provides a unique therapeutic strategy that more selectively targets plasma cells in patients with plasma cell myeloma.[1][1][⇓][2][⇓][3][⇓][4][⇓][5]-[6][6] While DARA recognizes and removes malignant

Anti-KEL sera prevents alloimmunization to transfused KEL RBCs in a murine model

Alloantibodies against red blood cell (RBC) antigens, which may be generated following exposure to foreign antigens on transfused RBCs or on fetal RBCs during pregnancy, can be clinically significant from the standpoint of morbidity and mortality.[1][1] In the transfusion setting, RBC alloantibodies

The role of immunohistochemical analysis in the evaluation of EML4-ALK gene rearrangement in lung cancer

Background:Among the mutations described in non–small cell lung carcinoma is a rearrangement resulting from an inversion within chromosome 2p leading to the formation of a fusion gene, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK). Fluorescence in situ hybridization (FISH) is the gold standard for the detection of ALK gene rearrangements. However, molecular methods are not readily available in all pathology laboratories. Immunohistochemistry (IHC) using an antibody directed against the EML4-ALK fusion protein provides a widely available alternative method of detection. We assessed whether IHC is a comparable and cost-effective alternative to FISH analysis for the detection of ALK gene rearrangements. Design:A total of 110 non–small cell lung carcinoma cases (63 surgical/biopsy and 47 cytology specimens), previously tested for ALK gene rearrangements by FISH [7 (6.4%) positive for the rearrangement], were probed for the EML4-ALK fusion protein using a monoclonal EML4-ALK antibody, clone 5A4. Cells were considered to stain positive for ALK if >5% of cells showed cytoplasmic staining of at least grade 1 intensity (scale: 0 to 3). A cost analysis was performed using ALK IHC as a screening test. Results:The sensitivity and specificity of the EML4-ALK IHC stain compared with ALK FISH analysis were 100% and 96%, respectively. All 7 FISH-positive cases stained positive by IHC, whereas 4 FISH-negative cases demonstrated positive staining. One of the 4 FISH-negative, IHC-positive cases harbored an EML4-ALK rearrangement by RT-PCR yielding 3 false-positive results overall. The &kgr; agreement between IHC and FISH methods is 0.76 (substantial/excellent). The potential savings of implementing the ALK IHC as a screening method would be

Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion.

10,418.21. Conclusions:Sensitivity of the EML4-ALK IHC stain is excellent (100%) but due to its suboptimal specificity, IHC cannot reliably supplant FISH analysis for the detection of ALK gene rearrangements. IHC shows promise as a screening tool to prevent unnecessary costly FISH analysis.

Unusual presentation of metastatic Ewing sarcoma to the ovary in a 13 year-old: a case report and review.

Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density. RBC alloantigens exist at different densities on the RBC surface and likewise exhibit distinct propensities to induce RBC alloantibody formation. However, although distinct alloantigens reside on the RBC surface at different levels, most alloantigens also represent completely different structures, making it difficult to separate the potential impact of differences in Ag density from other alloantigen features that may also influence RBC alloimmunization. To address this, we generated RBCs that stably express the same Ag at different levels. Although exposure to RBCs with higher Ag levels induces a robust Ab response, RBCs bearing low Ag levels fail to induce RBC alloantibodies. However, exposure to low Ag–density RBCs is not without consequence, because recipients subsequently develop Ag-specific tolerance. Low Ag–density RBC–induced tolerance protects higher Ag–density RBCs from immune-mediated clearance, is Ag specific, and occurs through the induction of B cell unresponsiveness. These results demonstrate that Ag density can potently impact immune outcomes following RBC transfusion and suggest that RBCs with altered Ag levels may provide a unique tool to induce Ag-specific tolerance.

Understanding solid-phase HLA antibody assays and the value of MFI

Ewing sarcoma (ES) is the second most common bone malignancy in children and adolescents. Together with primitive neuroectodermal tumors (PNET), ES comprises the PNET/ES family. Metastasis is present in about 25% of patients at diagnosis and is most commonly found in the lung and bones. Primary PNET/ES of the ovary has been reported in many adult cases; however, secondary occurrences are rare. Here we present the clinical course of a 13-year-old patient with metastatic ES to the ovary without involvement of any other sites. To our knowledge, this is the second reported pediatric case of metastatic ES to the ovary.

Triple-negative breast carcinoma in African American and Caucasian women: clinicopathology, immunomarkers, and outcome.

As the practice of medicine becomes more reliant on imaging and laboratory tests, medical decisions will be increasingly based on numbers. Accordingly, following the introduction of solid-phase testing to the HLA testing repertoire, laboratory directors and physicians have employed preset mean fluorescence intensity (MFI) thresholds as the basis for decisions in the management of transplant patients. However, what do MFI values mean? The literature is rife with reports detailing numerous factors that influence antibody assessment including (but not limited to) sensitization history of the patient, level of mismatch between donor and recipient, presence of interfering substances in the serum, whether the antigen on multiplex beads is native or denatured, day-to-day and technologist variability, and the historical performance of an assay in a given institution. How are these variables incorporated into the interpretation of MFI values? Herein, the pitfalls and complexities of single antigen bead (SAB) testing and interpretation are discussed with specific attention to what can and cannot be inferred by MFI.

Cytologic features of angiosarcoma: A review of 26 cases diagnosed on FNA

Purpose:Breast cancers are often classified on the presence/absence of hormone receptors, and growth factor oncogenes (estrogen receptor, progesterone receptor, HER2). Triple-negative breast cancers, negative for these markers, do not benefit from targeted therapy. We compared clinicopathologic parameters and immunohistochemical markers of prognostic and/or predictive significance, and outcome between African American and Caucasian triple-negative breast cancer patients. Methods:Invasive triple-negative breast cancers from African American (n=94) and Caucasian (n=68) patients were studied. Clinicopathologic features (age, tumor size, grade, lymph node status, angiolymphatic invasion, visceral metastases) and survival (overall and progression free) were compared. Marker expression (CK5, CK7, CK8, CK14, CK18, CK19, vimentin, CD44, c-Kit, epidermal growth factor receptor, p-cadherin, p53, p63, topoisomerase II, androgen receptor, Ki-67) was assessed in tissue microarrays. Results:Significant differences between African American and Caucasian women were observed for mean age and tumor size. African Americans had a trend toward greater lymph node involvement than Caucasians. The following markers were found in significantly different frequencies between the 2 groups: CK5, CK8, CK19, c-Kit, androgen receptor, and high Ki-67. African Americans show shorter overall and progression-free survival. Other clinicopathologic parameters, markers, and outcome were present at similar frequencies. Discussion:African American triple-negative breast cancers were more aggressive, occurring at a younger age, being larger, with higher proliferation, patients more frequently dying of disease, and with a trend toward positive lymph node status. Heterogeneity of marker expression suggests variation in the genetics of breast carcinomas in different races.