A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer.

BACKGROUND: To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC). METHODS: Twenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis. KMplotter was assessed to determine the association of the miRNAs with survival, and functional enrichment analysis to determine the main affected pathways and miRNA/mRNA target interactions. RESULTS: A panel of eight, 23 and 27 miRNAs were associated with tumor size, LN, and REC status, respectively. Combined ROC analysis of two (miR-2117, and miR-378c), seven (let-7f-5p, miR-1255b-5p, miR-1268b, miR-200c-3p, miR-520d, miR-527, and miR-518a-5p), and three (miR-1200, miR-1249-3p, and miR-1271-3p) miRNAs showed a robust discriminatory power based on tumor size (AUC = 0.917), LN (AUC = 0.945) and REC (AUC = 0.981) status, respectively. Enrichment pathway analysis revealed their involvement in proteoglycans and glycan and cancer-associated pathways. Eight miRNAs with deregulated expressions in patients with large tumor size, positive LN metastasis, and recurrence were significantly associated with lower survival rates. Finally, the construction of miRNA/mRNA networks based in experimentally validated mRNA targets, revealed nodes of critical cancer genes, such as AKT1, BCL2, CDKN1A, EZR and PTEN. CONCLUSIONS: Altogether, our data indicate that miRNA deregulated expression is a relevant biological factor that can be associated with the poor prognosis in TNBC of AA patients, by conferring to their TNBC cells aggressive phenotypes that are reflected in the clinical characteristics evaluated in this study.

Expanding Hospital Human Immunodeficiency Virus Testing in the Bronx, New York and Washington, District of Columbia: Results From the HPTN 065 Study.

Background: Human immunodeficiency virus (HIV) testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. Methods: To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. Results: From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of 1621016 ED visits and 13.0% of 361745 inpatient admissions in Bronx hospitals and 13.8% of 729172 ED visits and 22.0% of 150655 inpatient admissions in DC. From year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%; inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to 15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient tests were positive and 0.7% (189) were new diagnoses. Conclusions: Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive.

Differential expression of Annexin 2, SPINK1, and Hsp60 predict progression of prostate cancer through bifurcated WHO Gleason score categories in African American men.

BACKGROUND: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. METHOD: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5). AA men aged 41-90 diagnosed from 1990 to 2013 at Howard University were included. Automated staining assessed expression of each biomarker. Spearman correlation assessed the direction and relationship between biomarkers, WHO and modified WHO GS, age, and 5-year survival. A two-tailed t-test and ANOVA evaluated biomarkers expression in relationship to WHO normal and other GS levels, and between WHO GS levels. A logistic and linear regression analysis examined the relationship between biomarker score and WHO GS categories. Kaplan-Meier curves graphed survival. RESULTS: ANX2 expression decreased monotonically with the progression of PCa while expression of SPINK1/TATI and Hsp60 increased but had a more WHO GS-specific effect; SPINK1/TATI differed between normal and GS 2-6 and HSP60 differed between GS 7 and GS 2-6. WHO GS was found to be significantly and negatively associated with ANX2, and positively with SPINK1/TATI and Hsp60 expression. High SPINK1/TATI expression together with the low ANX2 expression at higher GS exhibited a bi-directional relationship that is associated with PCa progression and survival. CONCLUSION: Importantly, the data reveal that ANX2, and SPINK1/TAT1 highly associate with WHO GS and with the transition from one stage of PrCa to the next in AA men. Future research is needed in biracial and larger population studies to confirm this dynamic relationship between ANX2 and SPINK1 as independent predictors of PCa progression in all men.

MYC amplification in subtypes of breast cancers in African American women.

BACKGROUND: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. METHODS: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 < 14%), Luminal B (ER or PR+, Ki-67 = > 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling. RESULTS: Sixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 > 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p < 0.0001), stage (p < 0.001), metastasis (p < 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4). CONCLUSIONS: HER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa.

Expression of p27 and c-Myc by immunohistochemistry in breast ductal cancers in African American women.

OBJECTIVES: Proteins p27 and c-Myc are both key players in the cell cycle. While p27, a tumor suppressor, inhibits progression from G1 to S phase, c-Myc, a proto-oncogene, plays a key role in cell cycle regulation and apoptosis. The objective of our study was to determine the association between expression of c-Myc and the loss of p27 by immunohistochemistry (IHC) in the four major subtypes of breast cancer (BC) (Luminal A, Luminal B, HER2, and Triple Negative) and with other clinicopathological factors in a population of 202 African-American (AA) women. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 AA women. Five micrometer sections were stained with a mouse monoclonal antibody against p27 and a rabbit monoclonal antibody against c-Myc. The sections were evaluated for intensity of nuclear reactivity (1-3) and percentage of reactive cells; an H-score was derived from the product of these measurements. RESULTS: Loss of p27 expression and c-Myc overexpression showed statistical significance with ER negative (p < 0.0001), PR negative (p < 0.0001), triple negative (TN) (p < 0.0001), grade 3 (p = 0.038), and overall survival (p = 0.047). There was no statistical significant association between c-Myc expression/p27 loss and luminal A/B and Her2 overexpressing subtypes. CONCLUSION: In our study, a statistically significant association between c-Myc expression and p27 loss and the triple negative breast cancers (TNBC) was found in AA women. A recent study found that constitutive c-Myc expression is associated with inactivation of the axin 1 tumor suppressor gene. p27 inhibits cyclin dependent kinase2/cyclin A/E complex formation. Axin 1 and CDK inhibitors may represent possible therapeutic targets for TNBC.

Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of Unknown Significance in Early-Onset Breast Cancer in African American Women.

BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS: In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the potential function of each of the variants. RESULTS: Using next generation sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and 266 BRCA2 variants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14). CONCLUSIONS: Knowing a patient's BRCA mutation status is important for prevention and treatment decision-making. Improving the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Americans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies.

Papillary renal cell carcinoma with extensive spindle cell foci: mimicker of mucinous tubular and spindle cell carcinoma.

Papillary renal cell carcinoma (PRCC) is the second most common renal cell carcinoma (RCC), accounting for 10-15% of cases. Mucinous tubular and spindle cell carcinoma (MTSCC), on the other hand, accounts for only 1% of renal tumors and has a more favorable prognosis compared to PRCC. We report a 75-year-old female with a left upper pole solid renal mass displaying features of both papillary renal cell carcinoma (PRCC) and mucinous tubular and spindle cell carcinoma (MTSC). In this case, a shaggy luminal surface, multiple papillations, and psammoma bodies, absence of E-cadherin expression, and strong CD10 expression favored PRCC. Both immunohistochemistry and genomic analysis are critical to diagnose and differentiate tumors that may have overlapping features accurately.

Emerging infection: streptococcal toxic shock-like syndrome caused by group B Streptococcus (GBS), Streptococcus agalactiae.

Streptococcus agalactiae or Group B Streptococcus (GBS) infections are commonly associated with infections in neonates and pregnant women. However, there has been a rising incidence in nonpregnant adults. The risk of GBS infection in nonpregnant adults is increased for patients of advanced age and those with underlying medical conditions such as diabetes mellitus and cancer. We present a 77-year-old female with type-2 diabetes mellitus, hypertension, and bilateral foot ulcers that presented in probable septic shock with necrotic foot ulcers and necrotizing fasciitis and underwent bilateral lower limb amputations. The patient fulfilled the Streptococcal Toxic Shock Syndrome (STSS) criteria as defined by The Working Group on Severe Streptococcal Infections. These criteria were created for group A Streptococcus (Streptococcus pyogenes). Our patient fulfilled the Working Group's criteria, except that the blood culture was positive for group B Streptococcus (Streptococcus agalactiae). Numerous studies demonstrate the importance of early detection and antibiotic treatment for GBS infections in general and early surgical management for necrotizing soft tissue infections (NSTIs) such as necrotizing fasciitis.

Beyond Triple-Negative: High Prevalence of Quadruple-Negative Breast Cancer in African Americans.

Quadruple-negative breast cancer (QNBC) is a triple-negative breast cancer (TNBC) subtype that lacks expression of the androgen (AR) receptor. Few studies have focused on this highly aggressive breast cancer, portending worse survival rates. We aimed to determine the following: (1) QNBC's molecular and clinical characteristics and compare them with other subtypes and (2) QNBC's association with clinicopathological factors and prognostic markers. We performed immunohistochemical evaluations of ARs on tissue tumor microarrays from FFPE tumor blocks of invasive ductal breast carcinomas in 202 African American women. Univariate analysis was performed using the chi-square test, with survival rates calculated using Kaplan-Meier curves. Overall, 75.8% of TNBCs were AR-negative. Compared to the luminal subtypes, TNBC and QNBC tumors were likely to be a higher grade (p < 0.001); HER2+/AR- and QNBCs were also larger than the other subtypes (p < 0.001). They also expressed increasing mean levels of proteins involved in invasion, such as CD44, fascin, and vimentin, as well as decreasing the expression of proteins involved in mammary differentiation, such as GATA3 and mammaglobin. We found no association between QNBC and stage, recurrence-free survival, or overall survival rates. The high prevalence of TNBC AR-negativity in these women could explain observed worse outcomes, supporting the existence of the unique QNBC subtype.

Clostridioides difficile infection leading to fulminant colitis with toxic megacolon.

Clostridioidesdifficile infection (CDI) is the culprit of millions of nosocomial infections in the United States. Programs that successfully decrease its incidence, therefore, render cost savings for the healthcare system. Toxic megacolon and perforation are two of the most significant complications with increased mortality rates. We report a 23-year-old nursing home resident hospitalized for fever, cough, and green sputum. After 3 days of antibiotic therapy, he developed abdominal distension, diarrhea, and vomiting and underwent a total colectomy. The colon was dilated to a maximum of 11 cm with markedly edematous mucosa and yellow pseudomembranes. Qualitative PCR of the stool detected Clostridioides difficile toxin B gene. While there is no consensus for the required interval between antibiotic treatment and CDI, this presentation 3 days after starting the antibiotic therapy is earlier than most proposed ranges.

Necrotizing fasciitis and fatal septic shock associated with Streptococcus constellatus.

Streptococcus constellatus is usually a benign, commensal bacteria but has increased incidence in blood cultures and abscesses. This pathogenic involvement is most prevalent in individuals with underlying medical conditions, such as solid tumors and type 2 diabetes mellitus, as well as in cases of community-acquired infections. We report a 43-year-old male with a right medial thigh ulcer and necrotic scrotal skin. The wound culture from surgical debridement grew Streptococcus constellatus, and histology was consistent with stage III necrotizing fasciitis. Regardless of etiology, the mortality rate of patients with necrotizing fasciitis is greatly decreased with early intervention and thorough surgical debridement.

Aggressive Malignant Paraganglioma Involving the Pancreas and Vertebral Column.

Paraganglioma (PGL) is a rare neuroendocrine tumor arising from chromaffin cells outside the adrenal medulla. The most common sites are the abdomen and head and neck. Seventy percent (70%) of PGLs are sporadic, and 30% are hereditary; the latter are more often aggressive and malignant and occur in young adults. We report a case of a 36-year-old woman with a history of hypertension and abdominal pheochromocytoma resected at the age of 10 years who presented with back pain. Magnetic resonance imaging of the spine showed vertebral metastasis at L2-L5. Computed tomography of the abdomen showed a mass in the body of the pancreas and a laparoscopic biopsy was performed. The tumor cells had granular eosinophilic/basophilic cytoplasm and showed a nested pattern (Zellballen) with a prominent vascular network and infiltration of dense fibrous connective tissue. Strong and diffuse expression of synaptophysin in tumor cells, S100 expression in sustentacular cells at the periphery of nests, and lack of pancytokeratin expression supported the diagnosis of PGL. Due to limited tissue, it was difficult to determine metastatic vs primary neoplasm of the pancreas. The earlier age of onset and history of abdominal pheochromocytoma suggested the possibility of hereditary PGL associated with succinate dehydrogenase (SDH) deficiency. The tumor cells lacked SDHB expression. Germline mutation testing for SDH was recommended. The patient underwent palliative radiotherapy and systemic chemotherapy. Most PGLs are benign and asymptomatic, but there is an increased risk of cardiovascular mortality secondary to catecholamine secretion, and surgical excision is curative. Malignant PGLs are rare (10-40%), have poor prognosis, and are incurable. Increased size of the tumor, deep tissue infiltration, and high proliferative index increase the risk of malignancy, but metastasis is required for the diagnosis of malignant PGL. The advanced disease is treated with surgical removal of the tumor and combined radiotherapy and chemotherapy.

Characterization of GATA3 and Mammaglobin in breast tumors from African American women.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.

Characterization of GATA3 and Mammaglobin in breast tumors from African American Women.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Additional markers with improved specificity and sensitivity are warranted for triple negative breast tumors given the high prevalence in women of African descent.

Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer.

Background: Diagnosed invasive breast carcinomas in African American patients are more aggressive compared with those in Caucasian patients and diagnosed at later stages of the disease with higher grade tumors. Despite advances in breast cancer systemic treatment, new prognostic and predictive biomarkers are still needed. Therefore, potential biomarkers were chosen to correlate with different subtypes, recurrence, and survival of invasive breast cancer in a cohort of African American women. Methods: Eight protein biomarkers (ER, PR, HER2, Cyclin A2, Cytokeratin 5, Vimentin, Bcl2, and Ki-67) were evaluated using tissue microarrays (TMAs) and immunohistochemistry (IHC). The IHC results from TMAs were analyzed by both supervised and unsupervised clustering methods. The predictive clusters for the supervised and unsupervised methods were compared for agreement with the empirical classification. Kappa values were used to determine the overall percent correct clusters and agreement between specific clusters. Chi-square statistics was used to examine the association between hierarchical and multinomial logistic clustering methods. Results: Five subtypes of breast tumors with distinct protein expression patterns were identified among the studied 166 breast tumors. Luminal B tumors have been distinguished from luminal A tumors by staining for cell cycle proteins Cyclin A2 and Ki-67, which promote cell proliferation. Forty-nine percent were stained positive for Cyclin A2, 39.2% positive for Ki-67, and 37% positive for both Cyclin A2 and Ki-67. The age of patients did not show any significant effect whether five (p-value= 0.576) or eight (p-value= 0.605) biomarkers were used, which indicating that age did not have any influence on the classification of the subtypes. Ninety percent of the thirty triple negative tumors were positive for Cyclin A2 or Ki-67 or both. Six-year overall survival was better for luminal A tumors (76%) than luminal B tumors (71%). Likewise, six-year relapse-free survival was better for luminal A tumors (76%) than luminal B tumors (29%). Conclusion: Discovery of molecular markers such as Cyclin A2 and Ki-67, and subtypes that are most prevalent in African Americans could lead to a better understanding of the factors contributing to higher morbidity and mortality in this group and to aid in decision-making to offer earlier treatment.

PDJ amplicon in triple negative breast cancer.

Amplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1. Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 ≥ 2 and/or PDJ/9q34.1 ≥ 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ- TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC.

Inverse Correlation of KISS1 and KISS1R Expression in Triple-negative Breast Carcinomas from African American Women.

BACKGROUND/AIM: The kisspeptin 1 (KISS1) gene encodes a precursor polypeptide which after proteolysis forms the kisspeptin-10 (KISS1) protein. KISS1, retains maximum physiological activity when it binds to its receptor (KISS1R), allowing KISS1 to effectively function as a suppressor of metastasis in melanomas and other types of cancer. The goal of this study was to evaluate the expression of KISS1 and KISS1R in breast carcinomas from African American (AA) women and correlate their association with clinicopathological features, including breast cancer subtypes, and outcomes. MATERIALS AND METHODS: Tissue microarrays were constructed from formalin-fixed, paraffin-embedded surgical blocks from 216 AA patients. KISS1 and KISS1R expression was assessed using immunohistochemistry. Univariate analysis was used to determine the association between the expression of KISS1 and KISS1R, and clinicopathological characteristics. Pearson correlation was also determined between immunohistochemical H-scores, tumor size, and the number of positive lymph nodes. Kaplan-Meier estimates of overall and disease-free survival were plotted, and log-rank tests were performed to compare estimates among groups. RESULTS: KISS1 protein expression was found to be higher in receptor-negative and triple-negative breast cancer (TNBC) compared to other subtypes (p<0.001). However, KISS1R expression was higher in non-TNBC tumors compared to other subtypes (p<0.001). Higher KISS1R expression was marginally negatively correlated with tumor size (p=0.077), and positively correlated with lymph-node positivity (p=0.056), and disease-free survival (p=0.092). CONCLUSION: Our study showed a significant inverse correlation between KISS1 and KISS1R in TNBC. This investigation implicates a role for KISS1 and KISS1R in the pathogenesis of TNBCs in AA women.

Postmenopausal virilization secondary to a large ovarian cystadenoma with stromal hyperthecosis.

Ovarian cystadenomas may present in a functional manner. Biochemical workup of seemingly benign ovarian lesions should be considered in the appropriate clinical context.

Absence of Antibody Reponses and Severe COVID-19 in Patients on Hemodialysis Following mRNA Vaccination.

Inpatient dialysis patients cannot isolate, resulting in a higher rate of coronavirus disease 2019 (COVID-19) infections, with increased severity and higher mortality rate [1]. We present 2 African American dialysis patients who developed severe COVID-19 infections after vaccination. Both patients had not mounted antibody response to the COVID-19 vaccine or to hepatitis B vaccination.