Publications by authors named "Edward C Stack"
SPINK1 immunohistochemistry: An ancillary tool to diagnose urothelial carcinoma in situ and urothelial dysplasia.
Pathol Res Pract
September 2025
Expression of SPINK1 (Serine protease inhibitor Kazal type I), also known as tumor associated trypsin inhibitor (TATI), has been demonstrated in a wide spectrum of benign, inflammatory, and neoplastic conditions. Based on our prior results of its expression in urothelial carcinoma, in this study we further characterized SPINK1 expression in a spectrum of urothelial lesions and investigated its potential diagnostic utility. A total of 396 samples comprising a spectrum of urothelial lesions including benign, premalignant, and malignant lesions were evaluated for SPINK1 expression by immunohistochemistry and amplification by fluorescence in situ hybridization (FISH).
View Article and Find Full Text PDFThe presence of T regulatory (Treg) cells in the tumor microenvironment is associated with poor prognosis and resistance to therapies aimed at reactivating anti-tumor immune responses. Therefore, depletion of tumor-infiltrating Tregs is a potential approach to overcome resistance to immunotherapy. However, identifying Treg-specific targets to drive such selective depletion is challenging.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFArticle Synopsis
- The interaction between the immune system and tumor cells is crucial for understanding cancer prognosis and treatment, with new technologies like multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) helping to analyze immune cell dynamics within tumors.
- A task force from the Society for Immunotherapy of Cancer is working on guidelines to optimize and validate mIHC/mIF assays, bringing together experts from various fields including pathology and pharmaceuticals.
- mIHC/mIF technologies are set to become common in clinical settings for biomarker studies, and the emphasis on proper optimization and validation will help ensure reliable results across different labs and platforms.
Article Synopsis
- The study emphasizes the need for improved analysis methods of the tumor microenvironment (TME) to better stratify melanoma patients for immunotherapy, moving beyond traditional TIL analysis.
- Researchers utilized quantitative multiplex immunofluorescence (qmIF) to evaluate the proximity of cytotoxic lymphocytes (CTLs) and macrophages in melanoma tumors, finding that CTLs were significantly closer to activated macrophages than to nonactivated ones.
- Results indicated that higher CTL density and lower macrophage density in the tumor stroma correlated with better disease-specific survival, suggesting that the CTL/macrophage ratio could serve as a potential biomarker for predicting patient outcomes in melanoma treatment.
MYC Overexpression at the Protein and mRNA Level and Cancer Outcomes among Men Treated with Radical Prostatectomy for Prostate Cancer.
Cancer Epidemiol Biomarkers Prev
February 2018
Article Synopsis
- * Results show that while MYC protein was present in 97% of tumors and correlated with tumor proliferation, it did not have a strong association with lethal prostate cancer outcomes or other clinical indicators like stage or PSA levels.
- * Overall, the study concludes that MYC protein and mRNA overexpression are not reliable prognostic markers for prostate cancer in treated patients, making it one of the largest studies on this subject.
Article Synopsis
- - Signaling through programmed cell death protein 1 (PD-1) and its ligands (PD-L1, PD-L2) allows malignant Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) to avoid detection by the immune system.
- - HRS cells show increased expression of PD-L1 and PD-L2 due to genetic changes, and nonmalignant tumor-associated macrophages (TAMs) also express PD-L1, but their interactions with each other and with T cells are not well understood.
- - Research using advanced imaging techniques reveals that PD-L1 TAMs surround HRS cells in the tumor microenvironment, with a specific focus on interactions with CD4
Article Synopsis
- Melanoma is a serious skin cancer treated by removing the primary tumor and potentially doing a sentinel lymph node biopsy to check for metastasis, where identifying cancerous cells in lymph nodes is crucial for treatment decisions.
- The study investigates the effectiveness of two metabolic proteins, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), in distinguishing between metastatic melanoma and benign nodal nevi in patients.
- Results showed that all metastatic melanoma samples had significant staining for FASN and ACC, indicating their potential as biomarkers for identifying cancerous cells in sentinel lymph nodes.*
Novel technologies and emerging biomarkers for personalized cancer immunotherapy.
J Immunother Cancer
January 2016
Article Synopsis
- Recent advances in cancer immunotherapies are improving treatment outcomes for various types of cancer by leveraging the immune system to better control tumors.
- Despite these therapies' successes, not all patients benefit, and some face significant side effects, highlighting the need for better predictive and prognostic biomarkers.
- The Society for Immunotherapy of Cancer (SITC) formed a task force to explore new technologies and strategies for biomarker discovery, focusing on immune checkpoint blockade therapy and addressing challenges in current research.
Background: Combination platinum chemotherapy is standard first-line therapy for metastatic urothelial carcinoma (mUC). Defining the platinum response biomarkers for patients with mUC could establish personalize medicine and provide insights into mUC biology. Although DNA repair mechanisms have been hypothesized to mediate the platinum response, we sought to analyze whether increased expression of DNA damage genes would correlate with worse overall survival (OS) in patients with mUC.
View Article and Find Full Text PDFBackground: We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer.
Methods: Using data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n = 276).
Unlabelled: Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes.
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- Archival FFPE tissue specimens are underutilized resources for gene expression profiling, useful in discovering biomarkers, especially in cancer studies.
- This study compares two RNA expression profiling platforms—Affymetrix and NanoString—using FFPE tissues from prostate and ovarian cancer, revealing their high sensitivity and reproducibility regardless of specimen age.
- Both platforms produced similar gene expression results, supporting the use of archival specimens for large-scale biomarker validation in precision medicine.
Article Synopsis
- Researchers studied the DNA copy-number alterations in metastatic urothelial carcinoma, comparing 30 metastatic samples to 29 primary ones to understand progression from primary to metastatic disease.
- They found that metastases had significantly more genetic amplifications and deletions than primary tumors, with specific alterations like E2F3 amplification being more common in metastases.
- The findings suggest that differences in genetic changes between primary and metastatic tissues could be important for developing targeted cancer treatments in precision medicine.
Article Synopsis
- Tissue sections are crucial for understanding a patient's condition and improving treatment decisions, but much of their potential information remains untapped due to limited analytical methods.
- Current assessments often focus on a small number of proteins or genetic markers, missing out on valuable insights related to the spatial relationships and diversity of cells within tissues.
- The text reviews advanced techniques like multiparametric imaging and automated analysis that enhance the ability to extract detailed metrics from tissue samples, ultimately supporting personalized medicine through better data interpretation and pathologist engagement.
Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer.
Cancer Epidemiol Biomarkers Prev
October 2014
Background: The androgen receptor (AR) is an essential gene in prostate cancer pathogenesis and progression. Genetic variation in AR exists, including a polymorphic CAG repeat sequence that is inversely associated with transcriptional activity. Experimental data suggest that heightened AR activity facilitates formation of TMPRSS2:ERG, a gene fusion present in approximately 50% of tumors of patients with prostate cancer.
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- - FGFR3, often mutated or overexpressed in nonmuscle-invasive urothelial carcinoma, shows differing prevalence in muscle-invasive urothelial carcinoma with about 29% of primary tumors and 49% of metastases displaying FGFR3 protein expression.
- - FGFR3 mutations are relatively rare in both primary (2%) and metastatic (9%) tumors, while mutant tumors reveal significantly higher FGFR3 mRNA levels compared to wild-type tumors.
- - Changes in FGFR3 copy number are infrequent, with 0.8% in primary tumors and 3.0% in metastatic tumors, highlighting that while FGFR3 expression may be present, mutations and copy number variations are not common in muscle
Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates.
J Clin Oncol
June 2014
Article Synopsis
- The study investigated the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) with pegfilgrastim support in treating muscle-invasive urothelial cancer (MIUC).
- Out of 39 enrolled patients, 49% achieved a significant pathologic response, and 10% experienced high-grade toxicities, with no serious complications like neutropenic fevers or deaths reported.
- One-year disease-free survival rates were notably higher for patients with better response, indicating that ddMVAC can be an effective and well-tolerated treatment option for MIUC.
Article Synopsis
- Understanding genetic mechanisms of cancer therapy sensitivity could lead to better patient selection and treatment designs.
- A study identified a patient with advanced tumors who had an exceptional response to the drugs pazopanib and everolimus, showing remarkable effectiveness for 14 months.
- Genetic analysis revealed activating mutations in the mTOR pathway, suggesting that screening for these mutations could help identify more patients who would benefit from targeted mTOR therapies.
Purpose: Metastatic urothelial carcinoma of the bladder is associated with multiple somatic copy-number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy.
Experimental Design: We obtained overall survival (OS) and array DNA copy-number data from patients with metastatic urothelial carcinoma in two cohorts.
Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG.
J Natl Cancer Inst
December 2013
Background: TMPRSS2:ERG is a hormonally regulated gene fusion present in about half of prostate tumors. We investigated whether obesity, which deregulates several hormonal pathways, interacts with TMPRSS2:ERG to impact prostate cancer outcomes.
Methods: The study included 1243 participants in the prospective Physicians' Health Study and Health Professionals Follow-Up Study diagnosed with prostate cancer between 1982 and 2005.
Article Synopsis
- The study investigates castration resistance in prostate cancer by analyzing data from genetic mouse models and patient clinical data.
- It finds that removing certain genes (Trp53 or Zbtb7a) along with Pten leads to castration-resistant prostate cancer, while castration normally stops tumor growth.
- The research highlights specific gene expressions (XAF1, XIAP, SRD5A1) as potential indicators for treatment and suggests a combined therapy targeting these genes to overcome resistance.
Article Synopsis
- A study was conducted on patients with progressive glioblastoma (GBM) who previously received temozolomide to evaluate the effects of a dose-intense regimen.
- The study included 58 participants, with only 47 providing MGMT methylation results, showing that 65% had methylated tumors; however, the treatment led to limited responses.
- Although the intensified treatment was found to be safe, the results indicated only a small benefit in progression-free survival (11%), highlighting the need for better predictive biomarkers for future therapies.
Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention.
Cancer Discov
January 2013
Article Synopsis
- Prostate cancer presents a unique opportunity for chemoprevention, but current trials using 5α-reductase inhibitors have shown mixed results, leading to challenges in understanding their effectiveness.
- In a mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN), it was found that androgen deprivation methods, like surgical castration, may actually worsen disease progression to invasive castration-resistant prostate cancer (CRPC).
- Targeting the PI3K signaling pathway either genetically or with drugs showed promise in reversing negative effects of PTEN loss and effectively treating CRPC, suggesting that patients with PTEN-deficient tumors could benefit more from these targeted therapies rather than traditional antiandrogen treatments.*