Publications by authors named "Esther Elishaev"

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).

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Objective: Social determinants of health (SDOH) impact cancer outcomes. The CDC Social Vulnerability Index (SVI) integrates scores for four neighborhood-based SDOH domains (socioeconomic status, household characteristics, minority status, and housing type/transportation) to assess neighborhood social vulnerability (NSV). While NSV has been associated with overall cancer mortality and lung, breast, colon, and endometrial cancer-specific mortality, the relationship between NSV as defined by the SVI and ovarian cancer outcomes remains unknown.

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Background: Artificial intelligence (AI)-based systems are transforming cytopathology practice. The aim of this study was to evaluate the sensitivity of high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) diagnosis assisted by the Hologic Genius Digital Diagnostics System (GDDS).

Methods: A validation study was performed with 890 ThinPrep Pap tests with the GDDS independently.

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BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.

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Objectives: The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group-related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs).

Methods: SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs.

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Introduction: Intra-tumoral B cells mediate a plethora of immune effector mechanisms with key roles in anti-tumor immunity and serve as positive prognostic indicators in a variety of solid tumor types, including epithelial ovarian cancer (EOC). Several aspects of intra-tumoral B cells remain unclear, such as their state of activation, antigenic repertoires, and capacity to mature into plasma cells.

Methods: B lymphocytes were isolated from primary EOC tissue and malignant ascites and were maintained in cell culture medium.

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Article Synopsis
  • Elevated allostatic load (AL), which reflects cumulative physiological stress, is linked to increased mortality in various cancer patients, but its connection to ovarian cancer mortality was previously unknown.
  • This study analyzed data from 201 ovarian cancer patients to examine the relationship between high allostatic load and overall survival, using a robust statistical model to assess outcomes.
  • Results indicated that high allostatic load significantly correlated with increased mortality risk in ovarian cancer patients, suggesting it could be a useful marker for identifying those in need of additional socioenvironmental support during treatment.
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Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).

Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes.

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Fallopian tube pathology in patients with and mutations suggests a possible pathway to high grade serous ovarian carcinoma originates with a p53 signature, which is thought to represent a potential precursor to serous tubal intraepithelial carcinoma (STIC). The clinical implications of an isolated p53 signature in the average-risk population has not been well-established. This study aims to describe clinical outcomes in patients with incidentally noted p53 signature lesions.

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Article Synopsis
  • Researchers studied a common genetic change that happens in a type of ovarian cancer called high-grade serous carcinoma (HGSC), looking at how it affects patient survival.
  • They found that losing the RB1 protein was linked to longer survival in patients with HGSC, but it was the opposite for a different type of ovarian cancer called endometrioid cancer.
  • Patients with both RB1 loss and certain inherited genetic changes had much better survival rates compared to those with just one of these problems or none at all.
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  • The study explores the efficacy of the Ki67 proliferation marker in breast cancer treatment, highlighting issues with current scoring methods due to variability and time constraints.
  • Researchers used digital image analysis to quantify Ki67 indices in 280 breast cancer specimens as a potential solution for standardization and improved workflow.
  • The results showed strong agreement between digital analysis and manual counts, achieving an intraclass correlation coefficient of 0.96, indicating that digital image analysis could enhance Ki67 scoring accuracy.
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We present a case of uterine dedifferentiated leiomyosarcoma in a 42-yr-old woman who presented with severe abdominal pain and vaginal bleeding. The mass measured 10.5 cm.

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Introduction: Ovarian clear cell carcinoma (OCCC) is a rare subtype of ovarian epithelial carcinoma. Patients with low-stage disease have an excellent prognosis, while the prognosis for those with high-stage disease is poor. Neoplastic cells in abdominopelvic washings upstages the patient to at least FIGO 1C3.

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Objective: Endometrial cancer stage is a strong prognostic factor; however, the current stage classification does not incorporate transtubal spread as determined by intraluminal tumor cells (ILTCs). We examined relationships between ILTCs and survival outcomes according to histological subtype and stage and examined whether identification of ILTCs improves prognostic accuracy of endometrial cancer staging.

Methods: We conducted a retrospective cohort study of women diagnosed with endometrial cancer at five academic hospitals between 2007 and 2012.

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Objectives: Our aim was to explore the performance of TRPS1 as an immunohistochemical diagnostic marker; find the optimal conditions for its use in breast carcinomas, especially triple-negative breast cancers (TNBCs); and compare its results in carcinomas of a select few organ sites, with an emphasis on gynecologic tumors.

Methods: Tissue microarrays from breast carcinomas (n = 197), endometrial adenocarcinomas (n = 69), ovarian tumors (n = 250), vulvar squamous cell carcinomas (n = 97), pancreatic ductal adenocarcinomas (n = 20), and gastric adenocarcinomas (n = 12) were stained with TRPS1 using 2 different conditions (protocol 1: high pH; protocol 2: low pH). Breast carcinomas consisted of hormone receptor (HR)-positive/ERBB2 (formerly HER2 or HER2/neu)-negative (n = 53) samples, HR-positive/ERBB2-positive (n = 6) samples, and TNBCs (n = 138).

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Endometrial carcinoma is the most common extraintestinal cancer in Lynch syndrome (LS). Recent studies have demonstrated mismatch repair (MMR) deficiency can be detected in benign endometrial glands in LS. We performed MMR immunohistochemistry in benign endometrium from endometrial biopsies and curettings (EMCs) from a study group of 34 confirmed LS patients and a control group of 38 patients without LS who subsequently developed sporadic MLH1-deficient or MMR-proficient endometrial carcinoma.

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Introduction: In the past 2 decades, cervical cancer screening guidelines in the United States have undergone numerous revisions with recent greater emphasis on primary high-risk human papillomavirus (hrHPV) testing.

Materials And Methods: We examine the trends of Papanicolaou test and hrHPV testing at our large academic center across 4 years (2006, 2011, 2016, and 2021) over a 15-year period. The number of ThinPrep Papanicolaou and hrHPV tests, as well as the triggers for HPV testing, were retrospectively analyzed.

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Article Synopsis
  • The study aimed to investigate the relationship between p53 protein expression and survival rates in women with different types of ovarian cancer, particularly high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), and clear cell carcinoma (CCC), using a large cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium.
  • It was found that abnormal p53 expression patterns were prevalent in 93.4% of HGSC cases, but in EC and CCC, these abnormal patterns were linked to a significantly higher risk of death, indicating a poor prognosis.
  • The research concluded that while abnormal p53 expression doesn't affect survival in HGSC, it serves as a strong independent prognostic marker for EC and CCC,
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Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC.

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Background: Recently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.

Methods: Two prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively).

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Article Synopsis
  • Undifferentiated and dedifferentiated endometrial carcinomas (UDEC and DDEC) are rare, aggressive cancers of the uterus characterized by their lack of specific differentiation and associated mutations in SWI/SNF chromatin remodeling genes.
  • The study involved examining 20 cases, including immunohistochemical analysis of protein expression and next-generation sequencing to identify genetic mutations, revealing high tumor mutational burden and significant mutations in several key genes.
  • Findings showed a strong correlation between the presence of ARID1A mutations and the undifferentiated component of DDECs, while most cases demonstrated aggressive features such as advanced stage and lymphovascular invasion, highlighting the need for further research into these cancers.
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  • Advanced-stage mucinous ovarian carcinoma (MOC) is difficult to treat due to poor chemotherapy response and the need for better biomarkers for stage I treatment, leading researchers to analyze gene-expression and clinicopathologic data.
  • A study identified 19 genes potentially linked to patient prognosis, validating findings with data from 604 patients that included different types of tumors.
  • Results indicated that an infiltrative pattern of invasion correlates with worse survival, and higher levels of certain proteins (THBS2 and TAGLN) are associated with poor prognosis, suggesting both may be useful for determining treatment approaches.
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Unlabelled: Ovarian clear cell carcinoma (OCCC) is a deadly and treatment-resistant cancer, which arises within the unique microenvironment of endometriosis. In this study, we identified a subset of endometriosis-derived mesenchymal stem cells (enMSC) characterized by loss of CD10 expression that specifically support OCCC growth. RNA sequencing identified alterations in iron export in CD10-negative enMSCs and reciprocal changes in metal transport in cocultured OCCC cells.

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Background: Testosterone is one of the strategies that transmasculine persons can elect in order to align physical traits to their gender identity. Previous studies have shown morphologic changes in the genital tract associated with testosterone. Here, we aim to evaluate cervicovaginal cytology specimens (Pap tests) and high-risk HPV (HR-HPV) testing from transmasculine individuals receiving testosterone.

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Objectives: SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology-specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH).

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