Biopsies Of Patients Research Articles

Correlation Between Orofacial Pain and Sensory and Autonomic Neuropathies.

Orofacial Pain (OFP) affects 15% of the general population. OFP conditions can be myofascial, also known as temporomandibular disorders (TMDs) or neuropathic. The underlying pathophysiology in several chronic OFP conditions, is unknown. Small fiber neuropathy (SFN) is a disorder of thinly myelinated A-delta and non-myelinated C-fibers and can manifest as sensory and autonomic neuropathies. SFN has been demonstrated in some OFP conditions. Our study aims to assess the presence of OFP in patients with sensory and autonomic neuropathies and assess the correlation between OFP, skin biopsy and autonomic dysfunction. This is a retrospective study (2018-2020) of patients from the SFN registry, Massachusetts General Hospital, Boston, USA, for the presence of OFP. All patients were included. Primary outcome: Prevalence of OFP in patients with chronic neuropathies. Secondary outcomes: Correlation between OFP and skin biopsy, dysautonomia, headaches, chronic nociceptive pain, psychological conditions, and patient factors, such as mean age and BMI. Charts of 450 patients with sensory and autonomic neuropathies were reviewed. 22.67% (n=102) had OFP. The mean (range) age at biopsy in patients with OFP was 48.36 (20-81) years, female: male ratio 3.25:1. More OFP patients had negative skin biopsy results (p value<0.05) than those with sensory neuropathies. Patients with OFP had significantly higher prevalence of psychological conditions (p value 0.000), and higher BMI >30 (p value 0.025). Dysautonomia was significantly higher in patients with TMDs when compared to the ones without TMDs (p value 0.030). There was no significant difference in mean age, gender predilection, presence of headaches, peripheral neuropathies, and nociceptive pain between patients with and without OFP. OFP and sensory neuropathies can be overlapping conditions. Patients presenting with concomitant TMD and dysautonomia can be further tested for SFN. This can further help us understand a correlation if any, between idiopathic TMD/OFP conditions and SFN and further our understanding of the pathophysiology of these conditions.

504LBA (PB-504) LBA Posters: Monitoring of endogenous target occupancy in cells and patient biopsies using FCCS

504LBA (PB-504) LBA Posters: Monitoring of endogenous target occupancy in cells and patient biopsies using FCCS

A-222 Flow cytometry of skin biopsies in CTCL patients during Mogamulizumab treatment

A-222 Flow cytometry of skin biopsies in CTCL patients during Mogamulizumab treatment

Microbiome characterization of skin biopsies in Spanish patients with hidradenitis suppurativa shows a decrease in D1 and H1 lineages of Cutibacterium acnes.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder, with dysbiosis and loss of Cutibacterium acnes commonly observed in affected skin. This study analyzed the microbiome of lesional, perilesional, and healthy skin samples, finding significant differences, including increased Mycoplasma and Bacillus in lesional skin. The reduction of Cutibacterium variants D1 and H1 in HS-affected skin highlights their potential as therapeutic targets, suggesting a strategy of topical replacement therapy.

PPP3CB overexpression mediates EGFR TKI resistance in lung tumors via calcineurin/MEK/ERK signaling.

Despite initial high response rates to first-line EGFR TKI, all non-small-cell lung cancer (NSCLC) with EGFR-activating mutation will ultimately develop resistance to treatment. Identification of resistance mechanisms is critical to adapt treatment and improve patient outcomes. Here, we show that a PPP3CB transcript that encodes full-length catalytic subunit 2B of calcineurin accumulates in EGFR-mutant NSCLC cells with acquired resistance against different EGFR TKIs and in post-progression biopsies of NSCLC patients treated with EGFR TKIs. Neutralization of PPP3CB by siRNA or inactivation of calcineurin by cyclosporin A induces apoptosis in resistant cells treated with EGFR TKIs. Mechanistically, EGFR TKIs increase the cytosolic level of calcium and trigger activation of a calcineurin/MEK/ERK pathway that prevents apoptosis. Combining EGFR, calcineurin, and MEK inhibitors overcomes resistance to EGFR TKI in both in vitro and in vivo models. Our results identify PPP3CB overexpression as a new mechanism of acquired resistance to EGFR TKIs, and provide a promising therapeutic approach for NSCLC patients that progress under TKI treatment.

Challenge of Kidney Biopsy in Diabetic Patients: A Northwest Italy Large Cohort

Challenge of Kidney Biopsy in Diabetic Patients: A Northwest Italy Large Cohort

In vitro obtainment of stem-like cells from gubernaculum testis biopsies of cryptorchid pediatric patients

Testicular descent is a crucial event in male sexual development, and alterations in this process during gestation can lead to reduced fertility in adulthood. Cryptorchidism, i.e., failure of one or both testicles to descend into the scrotum, is one of the most common birth defects and represents a principal cause of infertility in adulthood. Therefore, identifying effective approaches for preserving fertility in childhood is of primary importance. In this context, the key role played by the gubernaculum testis during the placement of the testes in the scrotal bursa emerges. Given its close affinity to testicular tissue and its richness in mesenchymal cells, our prime aim is to characterize this para-testicular tissue to explore its potential ability to differentiate into testicular cells for fertility preservation. The first step of our task is represented by the present study that aimed to obtain in vitro stem-like cells starting from gubernaculum testis biopsies of four pediatric patients affected by cryptorchidism, aiming to differentiate them into testicular functioning cells. Our results show that the obtainment of aggregates with stem features is not dependent on the age of the patients and, therefore, not even on the damage suffered by the testis during its stay in the abdomen. This study opens the possibility of extending this approach to older patients, offering a new potential approach to support their fertility potential.

P2.04A.08 Feasibility of Cell-Free DNA Liquid Biopsy in Screening High-Risk Patients for Lung Cancer

P2.04A.08 Feasibility of Cell-Free DNA Liquid Biopsy in Screening High-Risk Patients for Lung Cancer

Assessing Chronicity Index on Kidney Biopsies of Patients with Lupus Nephritis and Its Correlation with Creatinine and Proteinuria at 1-Year Follow-Up

Assessing Chronicity Index on Kidney Biopsies of Patients with Lupus Nephritis and Its Correlation with Creatinine and Proteinuria at 1-Year Follow-Up

Comparison of the incidence of clinically significant prostate cancer in patients with isolated peripheral versus transitional zone PIRADS 3 lesions.

We sought to investigate the association between isolated PIRADS 3 lesions of the transitional zone (TZ) versus the peripheral zone (PZ) and the incidence of clinically significant prostate cancer (csPCa) on systematic and targeted prostate biopsy (SB, TB). We retrospectively reviewed our tertiary institutional database of patients who underwent mpMRI-fusion followed by TB + SB between 2016 and 2021. We compared the incidence of csPCa (Gleason Grade Group ⩾ 2) in patients with solitary TZ-only PIRADS 3 and PZ-only PIRADS 3 on SB and TB. We excluded patients with (1)known PCa, (2)PIRADS 4-5 and/or (3)lesions in both TZ and PZ. T-tests, Chi-square tests, were conducted to compare between the groups. Of 1913 patients, we identified 110 with PZ-only and 38 with TZ-only PIRADS 3 lesions. 73 patients in PZ-only and 19 in TZ-only met inclusion criteria. No statistically significant differences were observed between PZ and TZ groups in terms of age, median prostate-specific antigen (PSA), prostate volume, median PSA-density, or median number of targeted cores obtained, all with p > 0.05.On SB, the incidence of csPCA was higher in patients with PZ rather than TZ PIRADS-3 lesions (10/73 vs 1/19, p = 0.28). Similarly, csPCA was more common in TB of PZ versus TZ PIRADS 3 lesions (7/73 vs 0/19, p = 0.33). Based on these results, the positive predictive values of PIRADS3 as a marker of csPCA were 5.3% and 0% for TZ lesions on SB versus TB, respectively, compared to 17.7% and 9.6% in the PZ. PIRADS 3 lesions are rarely associated with csPCA on SB and TB, particularly when located in the TZ, which is an important factor to consider when deciding on a biopsy in patients with isolated TZ lesions.

Spleen shear wave elastography measurements do not correlate with histological grading of liver fibrosis in Fontan physiology: a preliminary investigation.

Elevated spleen stiffness may be seen in patients with portal hypertension due to cirrhosis. In patients with Fontan physiology, elevated liver stiffness has been shown to correlate poorly with liver fibrosis. It is unknown whether spleen stiffness may instead serve as a surrogate marker of liver fibrosis in these patients. To compare spleen stiffness determined by shear wave elastography (SWE) with histological findings of an ultrasound-guided liver biopsy in patients who had undergone Fontan palliation as a potential surrogate for Fontan-associated liver disease. This was an IRB-approved single-center, retrospective study. Patients with Fontan palliation who had undergone both a spleen SWE study and a percutaneous liver biopsy between 2016 and 2020 were included. Biopsy, performed during cardiac catheterization, within 3months of the SWE was required for inclusion. Using Kruskal-Wallis tests, spleen stiffness was compared with three liver biopsy scoring methods: Ishak, METAVIR, and congestive hepatic fibrosis score (CHFS). When available, Pearson's correlation was also used to compare collagen deposition determined using Sirius Red stain (%SR) with SWE values. A P-value < 0.05 was considered statistically significant. Twenty-two patients (15 males) were included in the study, with a median age of 17years (IQR is 14.8-20.5years; age range: 7years to 30.2years). The median spleen stiffness was 2.94m/s (IQR: 2.57-3.61m/s; range: 1.48-4.27m/s). The median Fontan pressure was 11mm Hg (IQR: 10-13.3mm Hg; range: 7-19mm Hg) obtained within a median of 10days (IQR: 1-41days) of SWE. Splenic stiffness did not correlate with the extent of fibrosis determined by histology (all P > 0.05). There was also no statistically significant correlation between the %SR staining and SWE-determined spleen stiffness (Pearson's correlation of 0.165, P = 0.59, n = 13). In this preliminary study, SWE spleen stiffness values did not correlate with biopsy-determined scoring of liver fibrosis in patients with Fontan physiology.

Isolated Primary Central Nervous System Lymphoma of the Optic Nerve: A Case Report and Review of the Literature.

Optic nerve involvement in primary central nervous system lymphoma (PCNSL) has been reported only a few times in the literature, with generally dismal outcomes. We focused on an extremely rare presentation of PCNSL in an immunocompetent patient with isolated manifestations of the optic nerve. A 72-year-old man presented with subacute vision loss in his left eye and optic disc swelling. Initial magnetic resonance imaging (MRI) of the orbits revealed a T2 hyperintense signal with enhancement of the left prechiasmatic optic nerve, suggestive of optic neuritis. He experienced visual improvement after 6 weeks of prednisone. However, 2 months after steroid tapering, he presented with worsening left-eye vision loss and new right-eye vision loss with imaging showing a peripherally enhancing chiasm lesion. A biopsy of the left optic nerve confirmed diffuse large B-cell lymphoma and negative systemic imaging was consistent with PCNSL. He was treated with high-dose methotrexate, rituximab, procarbazine vincristine (R-MVP), and cytarabine (AraC) with some visual improvement in the right eye and resolution of previously seen enhancement on MRI. The patient is in remission with no further deterioration of his vision. This is the first reported case of isolated optic nerve involvement with a durable response to chemotherapy. This case emphasizes the importance of considering malignancy and maintaining a low threshold for optic nerve biopsy in patients with atypical cases of severe steroid-refractory vision loss with enhancement or enlargement of the optic nerve on MRI. Standard chemotherapy regimens for PCNSL can potentially achieve a curative response in these patients.

Indocyanine green and methylene blue dye guided sentinel lymph node biopsy in patients with penile cancer (PeCa): results of 50 inguinal basins assessed at a single institution in India.

The primary aim of this study was to validate the reliability, sensitivity and safety profile of novel combination of ICG- methylene blue dye as an SN tracer for PeCa. This is a validation and non-randomised prospective observational study involving 25 patients (50 inguinal basins) who underwent SLNB where in ICG and methylene blue were used for localisation. The patients with clinically node negative groins were recruited in the study. SNs were identified intraoperatively using near infrared fluorescence imaging (NIRF Imaging system, SPY-PHI, Stryker, Sweden) and blue dye. The numbers of SNs identified by each tracer and the rates of complications and nodal recurrence during the followup. Overall 137 SNs were identified intraoperatively. Among the 137 SNs excised fluorescence, blue dye and Combined (blue + green) identified 57(41.6%), 27 (19.7%), and 51 (37.2%), respectively. The average number of SLNs removed per patient was 5 (range, 1-11) with sentinel lymph nodes detection rate at 94% (47/50). Seven patients had malignancy on SLNB and underwent ipsilateral radical inguinal lymphadenectomy. One patient had false negative SN and positive node in modified inguinal lymphadenectomy specimen. No adverse events were observed in all cases. The Novel combination of ICG fluorescence-Methylene blue dye technique is simple, reliable and safe. Moreover, it demonstrates a high SLN detection rate with a low false-negative rate, and it avoids radiation exposure.

PCR-based RFLP and ERIC-PCR patterns of Helicobacter pylori strains linked to multidrug resistance in Egypt.

H. pylori infects approximately 50% of the world's population that causes chronic gastritis, and may lead to peptic ulcer disease (PUD). H. pylori-induced chronic infections are associated with gastric adenocarcinoma and low-grade gastric lymphoma. In Egypt, H. pylori strains are widespread and became resistant to antimicrobial agents, thus advanced typing methods are needed to differentiate infectious strains that are resistant to antibiotics, and therefore earlier prognosis and infection control. The main objectives were (i) to determine susceptibility of infectious H. pylori strains to some antimicrobial agents that are currently used in eradication therapy in Egypt; (ii) to identify diverse strains commonly detected in the gastrointestinal (GIT) endoscopy units in Egypt through phenotypic and genotypic analyses. In this observational study we isolated 167 isolates from 232 gastric biopsies (antrum and corpus) of patients who were admitted to the upper GIT endoscopy units in five governmental Egyptian hospitals. Antimicrobial susceptibility patterns were investigated using Kirby Bauer disc diffusion and agar dilution Minimum Inhibitory Concentrations (MICs) methods. Phenotypic characterization was based on biotyping and antibiogram typing techniques. Genotypic characterization was carried out using PCR-based Restriction Fragment Length Polymorphism (RFLP) and Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR analyses. H. pylori isolates were highly resistant to diverse antimicrobial agents including Metronidazole, Fluoroquinolones, Macrolides, Amoxycillin, Tetracycline and Gentamicin. Two factors contributed to the increased resistance of H. pylori to the conventional therapy seen in Egypt: (i) Metronidazole and Amoxycillin are inexpensive and available drugs being abused by patients; (ii) the regional prescribing practice of Macrolids commonly used to treat upper respiratory and urinary tract infections. Five different biotypes were identified depending on the ability of the isolates to synthesize different enzymes. Nine antibiogram types were identified. PCR-RFLP analysis revealed fifteen different fingerprints while ERIC-PCR revealed 22 fingerprints. Biotyping alone or in combination with antibiogram typing are highly useful molecular tools in the prognosis of strain relatedness. PCR-RFLP and ERIC-PCR acquired good discriminatory power for identifying H. pylori infectious sub-types.

Magnetic lymphatic tracing for omission of sentinel lymph node biopsies in mastectomy patients: a community cancer center experience.

Patients with ductal carcinoma in situ (DCIS) and patients undergoing risk reduction mastectomy may undergo sentinel lymph node biopsy (SLNB) at the time of mastectomy to complete axillary staging were an underlying invasive malignancy to be found on final pathology. Among patients with DCIS undergoing mastectomy, 15-29% of patients will have invasive disease on final pathology; therefore, approximately 70-85% of patients may benefit from avoiding SLNB. Superparamagnetic tracers (SPMT) have been proven to be non-inferior to the standard radioisotope and blue dye combination. SPMT remains active for several weeks, allowing a large proportion of DCIS and genetic carrier patients to potentially avoid SLNB in the setting of mastectomy. We hypothesize the use of SPMT will reduce the number of SLNB performed in patients undergoing mastectomy for DCIS and risk reduction, ultimately reducing the number of complications associated with axillary surgery. We seek to report our community cancer center's experience with SPMT and omission of SLNB in the DCIS and prophylactic mastectomy patient population. We performed a retrospective review of 52 female patients with DCIS or known genetic predisposition undergoing mastectomy. SPMT (Magtrace®, Endomag Ltd, Cambridge, UK) was injected ipsilateral to DCIS and bilaterally for prophylactic mastectomy patients. Our primary outcome was rate of return to the operating room (OR) for delayed SLNB. Secondary outcomes included post-operative complications within 30days of surgery and operative time. We compared outcomes to a control group of 28 women undergoing mastectomy for DCIS or for risk reduction who underwent SLNB at their index operation in traditional fashion. Continuous variables were reported using median and interquartile ranges (IQR) and were compared using the Mann-Whitney U test. Categorical data were reported using frequency and percent and were compared using Pearson's Chi-Square or Fisher's Exact test, as appropriate. Alpha was set to 0.05 to determine statistical significance. There was a total of 80 patients (52 SPMT, 28 control). Median age of SPMT patients was 49.5 (IQR 40-60.75) vs. 54.5 (48 - 65) in the traditional tracer group. vs. control group. 57.7% of SPMT patients underwent mastectomy for DCIS vs. 89.3% in the control group. Eight SPMT patients (15.4%) had invasive ductal carcinoma (IDC) on final pathology and seven of those patients underwent delayed SLNB (87.5%). None of the delayed SLNB were positive for metastatic disease. Rates of post-operative complications were similar between the two groups, including hematoma, seroma, and surgical site infection. OR times were also similar with median OR time 202min (min) for the SPMT group vs. 195min for the control group. Use of SPMT avoided SLNB in 84.6% of our patients. We found no difference in rates of post-operative complications or operative times in patients using SPMT for omission of SLNB at time of mastectomy compared to the control group. Our findings suggest SLNB can be avoided in a majority of patients undergoing mastectomy for DCIS or risk reduction in the setting of genetic predisposition.

Correlation Between Clinical Assessment and Postmortem Lung Biopsy in Patients With Pulmonary Infiltrates and Respiratory Failure.

Pulmonary complications commonly cause mortality in critically ill patients with acute and chronic liver diseases in the intensive care unit. Pneumonia is the most common clinical diagnosis supported by radiological and microbiological results, which are subjective and often with poor yield. The study aimed to correlate clinical diagnosis and postmortem lung histology in patients with liver disease with respiratory failure. Records of acute and chronic liver disease patients with respiratory failure-associated mortality and postmortem lung biopsy from September 2009 to March 2020 were analyzed. Clinical diagnosis supported by radiological and/or microbiological data was compared with histology. One hundred eight patients (age 46.83±12.96 years), males 80 (74.1%), 63 (58.3%) cirrhosis of the liver, 30 (27.8%) acute-on-chronic-liver-failure, and 9 (8.3%) acute liver failure, were analyzed. Of the 76 patients (70.37 % of the total) with pneumonia, 33 (43.4 %) had histological evidence of pneumonia. Other histological diagnoses in these patients were normal or nonspecific changes in 27 (35.5 %) and alveolar hemorrhage in 13 (17.1 %). In the remaining 32 patients, histological diagnosis of pneumonia was evident in nine patients (28.1%). Using postmortem histology as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive valuefor clinical diagnosis of pneumonia were found to be 78.57%, 34.85%, 43.42%, and 71.88% respectively. The kappa statistics for agreement between the two was 0.12 (95% C.I. -0.04 to 0.27) suggesting poor agreement. Age and histological pneumonia predicted significant missed diagnosis. There is poor agreement between clinical diagnosis and postmortem histology. Postmortem lung biopsy helps with the unexplained cause of death.

Communication between cancer cell subtypes by exosomes contributes to nasopharyngeal carcinoma metastasis and poor prognosis.

Intratumor heterogeneity is common in cancers, with different cell subtypes supporting each other to become more malignant. Nasopharyngeal carcinoma (NPC), a highly metastatic cancer, shows significant heterogeneity among its cells. This study investigates how NPC cell subtypes with varying metastatic potentials influence each other through exosome-transmitted molecules. Exosomes were purified and characterized. MicroRNA expression was analyzed via sequencing and qRT-PCR. The effects of miR-30a-5p on migration, invasion, and metastasis were evaluated in vitro and in vivo. Its impact on desmoglein glycoprotein (DSG2) was assessed using dual-luciferase assays and Western blotting. Immunohistochemistry (IHC) and statistical models linked miR-30a-5p/DSG2 levels to patient prognosis. Different NPC cell subtypes transmit metastatic potential via exosomes. High-metastatic cells enhance the migration, invasion, and metastasis of low-metastatic cells through exosome-transmitted miR-30a-5p. Plasma levels of exosomal miR-30a-5p are reliable indicators of NPC prognosis. miR-30a-5p may promote metastasis by targeting DSG2 and modulating Wnt signaling. Plasma exosomal miR-30a-5p inversely correlates with DSG2 levels, predicting patient outcomes. High-metastatic NPC cells can increase the metastatic potential of low-metastatic cells through exosome-transmitted miR-30a-5p, which is a valuable prognostic marker assessable via liquid biopsy.

Cardiomyocyte-derived circulating extracellular vesicles allow a non-invasive liquid biopsy of myocardium in health and disease.

The ability to track disease without tissue biopsy in patients is a major goal in biology and medicine. Here, we identify and characterize cardiomyocyte-derived extracellular vesicles in circulation (EVs; "cardiovesicles") through comprehensive studies of induced pluripotent stem cell-derived cardiomyocytes, genetic mouse models, and state-of-the-art mass spectrometry and low-input transcriptomics. These studies identified two markers (POPDC2, CHRNE) enriched on cardiovesicles for biotinylated antibody-based immunocapture. Captured cardiovesicles were enriched in canonical cardiomyocyte transcripts/pathways with distinct profiles based on human disease type (heart failure, myocardial infarction). In paired myocardial tissue-plasma from patients, highly expressed genes in cardiovesicles were largely cardiac-enriched (vs. "bulk" EVs, which were more organ non-specific) with high expression in myocardial tissue by single nuclear RNA-seq, largely in cardiomyocytes. These results demonstrate the first "liquid" biopsy discovery platform to interrogate cardiomyocyte states noninvasively in model systems and in human disease, allowing non-invasive characterization of cardiomyocyte biology for discovery and therapeutic applications.

Abstract A039: Joint roles of proteomics and neighborhood-level social determinants of metastatic prostate cancer

Abstract Introduction: Striking racial disparities in prostate cancer (PCa) outcomes among American Black men warrant significant efforts to identify early predictors of lethal PCa, to avoid over- treatment of clinically favorable disease with minimal risk of progression. Building on prior work, this study examined independent and joint roles of proteomic markers and social determinants of health (SDOHs) in predicting prostate disease aggressiveness in a racially diverse cohort of men undergoing prostate biopsy. Methodology: A retrospective cohort of 300 men biopsied for prostate cancer was assembled at University Hospitals (UH) Seidman Cancer Center in Cleveland, Ohio between January 1, 2005-May 2022. An extensive medical chart review was performed to identify Black and White men undergoing transrectal ultrasound- guided biopsy that resulted in: (i) a negative biopsy in patients with a history of 1+ prior negative biopsy and no PCa history (“NEG”); (ii) a biopsy-detected PCa of Gleason sum 6 (“GL6”); and (iii) biopsy-detected PCa with nodal and/or distant metastases at initial cancer detection (“METS”). Prostate biopsy tissues were obtained on each patient, balancing 100 men per biopsy group, and balanced on race (1:1) within each biopsy group. Informed by findings from an untargeted analysis of the entire proteome of 60 patients (“Discovery cohort”), we conducted a targeted proteomics analysis of 16 protein markers generated from prostate biopsy tissue, using mass spectrometry, on n=240 patients (“Verification cohort”). Chi-square testing and Analysis of Variance (ANOVA) were used to assess associations between protein expression, neighborhood-level SDOHs, and biopsy group. Race-stratified analyses were performed to examine statistical interactions between study associations. Principal components (PC) analysis was used to identify protein markers that predicted the greatest variance in biopsy group. Multivariable logistic regression (MLR) was used to predict METS (vs. NEG and GL6, combined), as a function of PC-selected protein markers and census block-group level area deprivation index (ADI). Bonferroni correction was used to establish the threshold for the decision rule of statistical significance (alpha error 0.05/16 markers: p&amp;lt; 0.0031). Results: Median patient age was 68 years. Protein expression distributions were transformed into quintiles due to non-normality. Of 16 protein markers, 14 were significantly correlated with biopsy group, including PARP 1 and TGFB1, for which METS patients had the highest expression. ADI was strongly correlated with race but not protein expression. ADI was significantly higher in METS patients, followed by GL6 and lowest in NEG group; however no associations were seen for ADI with protein expression. Eight proteins were found to predict METS in PC and MLR analysis. Conclusions: These data support use of proteomics markers to predict a metastatic versus non-metastatic biopsy result. Next steps include deep exploration of proteome findings generated in the Discovery cohort, such as biological pathways. Citation Format: Jennifer Cullen, Tao Liu, Holly Hartman, Fangzhou Liu, Anood Alfahmy, Rini Ghosh, Ayesha Shafi, Julia Payne, Randy Vince, Lee Ponsky, Gregory MacLennan. Joint roles of proteomics and neighborhood-level social determinants of metastatic prostate cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A039.

A study of PGP 9.5 immunohistochemical labeling on formalin-fixed paraffin embedded tissues for epidermal nerve fiber density testing

ABSTRACT There have been several methods established for immunohistochemical labeling of the PGP 9.5 antigen in human tissue for the assessment of epidermal nerve fiber density, none of which uses neutral-buffered formalin as the preferred fixative for paraffin-embedded tissue. The literature maintains that formalin-fixed paraffin embedded tissues are unable to be used for this purpose and that other fixatives must be used due to the cross-linkages caused by formalin fixation. This study was undertaken to develop a standardized method for the use of formalin-fixed paraffin embedded tissues for immunohistochemical labeling and assessment of epidermal nerve fiber density. Formalin-fixed paraffin embedded tissues from the punch biopsies of patients suspected to have small fiber neuropathy were prepared for immunohistochemical labeling using heat-induced epitope retrieval for one hour at 92°C. The tissues were then stained with a polyclonal rabbit anti-human PGP 9.5 primary antibody. The resulting stains were then evaluated by a licensed pathologist who counted the number of epidermal nerve fibers stained and recorded the epidermal length in millimeters. Human foreskin was used as the tissue control in these studies. Satisfactory immunohistochemical labeling of epidermal nerve fibers was achieved from formalin-fixed paraffin embedded tissues through the use of heat-induced epitope retrieval. The authors of this paper have concluded that formalin-fixed paraffin embedded tissues may be used to achieve satisfactory immunohistochemical labeling for the assessment of epidermal nerve fiber density.