Faculty Bibliography

In diagnostic breast pathology, there is no reliable applicable immunostain to help discern atypical and in situ apocrine lesions from benign apocrine tissue. At present, the diagnosis of non-invasive apocrine lesions remains challenging with current diagnoses rendered based on discrete morphologic characteristics on conventional hematoxylin and eosin staining. Interobserver variability is significant even among subspecialists partly due to lack of adjuvant diagnostic immunohistochemical stains. Herein, we set to elucidate the potential utility of EZH2 and Ki-67 immunostains as tangible tools in non-invasive apocrine proliferations. A cohort of apocrine breast lesions [Benign apocrine hyperplasia (BAH), n = 10; Atypical apocrine hyperplasia (AAH), n = 16; Apocrine ductal carcinoma in situ (ADCIS), n = 12] were subjected to EZH2 immunostaining and analyzed via H-scoring of nuclear expression. Mean H-scores for EZH2 progressively increased from BAH (23.5), to AAH (47.4) and ADCIS (196.4), and showed a significant difference utilizing the Kruskal-Wallis test (p < 0.0001). Further interrogation of Ki-67 demonstrated incremental expression from BAH to AAH and ADCIS at 1.6 %, 4.7 % and 24.7 %, respectively (p < 0.0001, Kruskal-Wallis test), suggesting an association with increased proliferation. Our results demonstrate that a combination of EZH2 and Ki-67 immunostaining may be employed in differentiating among challenging apocrine breast lesions and suggest a putative diagnostic utility for EZH2 and Ki-67 in non-invasive apocrine breast lesions.

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.ajpath.2020.07.001. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Background: The Mediator Complex (MED) is a large multi-subunit protein which interacts directly with RNA Polymerase II and transcription factors for general regulation of protein expression. Recently, Mediator Complex 7 (MED7) has been shown to be underexpressed in high grade invasive mammary carcinomas in comparison to lower grade invasive carcinomas. No study has yet investigated the expression of MED7 in ductal carcinoma in situ (DCIS). In our study, we set out to evaluate the biological significance of MED7 in DCIS.
Design(s): MED7 immunostaining was performed with a rabbit monoclonal antibody (EPR15410, Abcam- Ab187146, Cambridge, UK). The H-score method was utilized for quantifying MED7 nuclear expression in DCIS. This method combines nuclear staining intensity and the percentage of positive cells. Staining intensity (0-3) is multiplied by percentage of positive DCIS cells (0-100) leading to the H-score, with a range of 0-300 for each case. We investigated breast core biopsies with DCIS; 20 were high grade, 14 were intermediate grade, and 15 were low grade. The hormone receptor status of each case was also recorded. GraphPad PRISM 7.0 software was used for statistical analysis.
Result(s): The mean H-Score for high grade DCIS cases was 146, intermediate grade was 219, and low grade was 228 (p <0.0001, Kruskal-Wallis test). The mean H-score for high grade DCIS cases was significantly lower than that of low and intermediate grade DCIS (p <0.0001 and p = 0.0004, respectively, Dunn's test). The MED7 H-Score was significantly lower in ER negative cases compared to that seen in ER positive cases (p <0.0001). Area under the curve (AUC) in the ROC curve for MED7 H-Scores in high grade versus non-high grade DCIS cases was 0.9276 (p <0.0001). (Table presented)
Conclusion(s): Our results suggest that MED7 expression is significantly down regulated in high grade and ER-negative DCIS cases, thus implying a significant biological role of MED7 in the progression of DCIS. Taken together, our data establishes MED7 H-score as a tangible tool for evaluating high grade DCIS. Further studies are underway to establish a practical cut-off value for the MED7 H-Score for high grade DCIS. We believe that these important early steps investigating MED7 are crucial in clarifying its important role in the development and progression of breast and other cancers