Effect of formalin fixation on measured concentrations of deposited gadolinium in human tissue: an autopsy study

Background Generally, studies of gadolinium (Gd) deposition in humans measure concentration by analyzing formalin fixed postmortem tissue. However, the effect of formalin fixation on measured Gd concentration has not been well investigated. Purpose To evaluate the effect of fixation by comparing Gd concentration in fresh versus formalin-fixed postmortem human tissues. Material and Methods Fresh samples of bone and skin were collected from autopsy cases with previous exposure to Gd-based contrast agents (GBCAs). The type of GBCA administered, dose, and estimated glomerular filtration rate were recorded. Each tissue sample was cut into three aliquots. Paired samples were stored fresh frozen while the remaining two were stored in 10% neutral buffered formalin for one and three months, respectively. Gd concentration was measured using ICP-MS. Results Of 18 autopsy cases studied, 12 were exposed to only macrocyclic GBCA, one to only linear agents, and five received both macrocyclic and linear agents. On average, Gd concentration for bone decreased 30.7% after one month of fixation ( P = 0.043) compared to non-fixed values. There was minimal, if any, change in concentration between one and three months (average decrease 1.5%; P = 0.89). The findings were numerically similar for skin tissue with an average decrease of 36.9% after one month ( P = 0.11) and 6.0% ( P = 0.73) between one and three months. Conclusion Formalin fixation appears to decrease Gd concentration in bone and skin by approximately 30%–40% on average. The largest decrease occurs within the first 30 days of fixation followed by a considerably smaller decrease at 60 days.

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Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples

Experimental Biology and Medicine ◽

10.1177/1535370217736512 ◽

2017 ◽

Vol 242 (18) ◽

pp. 1802-1811 ◽

Cited By ~ 15

Author(s):

Xuan Dung Ho ◽

Phuong Phung ◽

Van Q Le ◽

Van H Nguyen ◽

Ene Reimann ◽

...

Keyword(s):

Extracellular Matrix ◽

Collagen Biosynthesis ◽

Normal Bone ◽

Paired Samples ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Fresh Frozen ◽

Whole Transcriptome Analysis ◽

Whole Transcriptome ◽

Formalin Fixed

We performed whole transcriptome analysis of osteosarcoma bone samples. Initially, we sequenced total RNA from 36 fresh-frozen samples (18 tumoral bone samples and 18 non-tumoral paired samples) matching in pairs for each osteosarcoma patient. We also performed independent gene expression analysis of formalin-fixed paraffin-embedded samples to verify the RNAseq results. Formalin-fixed paraffin-embedded samples allowed us to analyze the effect of chemotherapy. Data were analyzed with DESeq2, edgeR and Reactome packages of R. We found 5365 genes expressed differentially between the normal bone and osteosarcoma tissues with an FDR below 0.05, of which 3399 genes were upregulated and 1966 were downregulated. Among those genes, BTNL9, MMP14, ABCA10, ACACB, COL11A1, and PKM2 were expressed differentially with the highest significance between tumor and normal bone. Functional annotation with the reactome identified significant changes in the pathways related to the extracellular matrix degradation and collagen biosynthesis. It was suggested that chemotherapy may induce the modification of ECM with important collagen biosynthesis. Taken together, our results indicate that changes in the degradation of extracellular matrix seem to be an important mechanism of osteosarcoma and efficient chemotherapy induces the genes related to bone formation. Impact statement Osteosarcoma is a rare disease but it is of interest to many scientists all over the world because the current standard treatment still has poor results. We sequenced total RNA from 36 fresh-frozen paired samples (18 tumoral bone samples and 18 non-tumoral paired samples) from osteosarcoma patients. We found that differences in the gene expressions between the normal and affected bones reflected the changes in the regulation of the degradation of collagen and extracellular matrix. We believe that these findings contribute to the understanding of OS and suggest ideas for further studies.

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Quantifying the Effects of Formalin Fixation on the Mechanical Properties of Cortical Bone Using Beam Theory and Optimization Methodology With Specimen-Specific Finite Element Models

Journal of Biomechanical Engineering ◽

10.1115/1.4034254 ◽

2016 ◽

Vol 138 (9) ◽

Cited By ~ 6

Author(s):

Guan-Jun Zhang ◽

Jie Yang ◽

Feng-Jiao Guan ◽

Dan Chen ◽

Na Li ◽

...

Keyword(s):

Finite Element ◽

Beam Theory ◽

Optimization Method ◽

Formalin Fixation ◽

Theory Method ◽

Fe Method ◽

Three Point Bending ◽

Fresh Frozen ◽

Optimization Methodology ◽

Formalin Fixed

The effects of formalin fixation on bone material properties remain debatable. In this study, we collected 36 fresh-frozen cuboid-shaped cortical specimens from five male bovine femurs and immersed half of the specimens into 4% formalin fixation liquid for 30 days. We then conducted three-point bending tests and used both beam theory method and an optimization method combined with specimen-specific finite element (FE) models to identify material parameters. Through the optimization FE method, the formalin-fixed bones showed a significantly lower Young's modulus (−12%) compared to the fresh-frozen specimens, while no difference was observed using the beam theory method. Meanwhile, both the optimization FE and beam theory methods revealed higher effective failure strains for formalin-fixed bones compared to fresh-frozen ones (52% higher through the optimization FE method and 84% higher through the beam theory method). Hence, we conclude that the formalin fixation has a significant effect on bovine cortical bones at small, elastic, as well as large, plastic deformations.

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Faculty Opinions recommendation of A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726361618.793528010 ◽

2017 ◽

Author(s):

Alexandre Alanio

Keyword(s):

Mammary Tumors ◽

Dna Assay ◽

Branched Dna ◽

Canine Mammary Tumors ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Fresh Frozen ◽

Formalin Fixed

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The Dutch National TissueArchive Portal enables efficient, consistent, and transparent procurement of diagnostic tissue samples for scientific use

Cell and Tissue Banking ◽

10.1007/s10561-021-09949-1 ◽

2021 ◽

Author(s):

Robin Verjans ◽

Annette H. Bruggink ◽

Robby Kibbelaar ◽

Jos Bart ◽

Aletta Debernardi ◽

...

Keyword(s):

The Netherlands ◽

Tissue Sample ◽

Ffpe Tissue ◽

Tissue Samples ◽

Internet Portal ◽

Formalin Fixed Paraffin ◽

Practical Support ◽

Formalin Fixed Paraffin Embedded ◽

The Rich ◽

Formalin Fixed

AbstractBiobanks play a crucial role in enabling biomedical research by facilitating scientific use of valuable human biomaterials. The PALGA foundation—a nationwide network and registry of histo- and cytopathology in the Netherlands—was established to promote the provision of data within and between pathology departments, and to make the resulting knowledge available for healthcare. Apart from the pathology data, we aimed to utilize PALGA’s nationwide network to find and access the rich wealth of Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples for scientific use. We implemented the Dutch National TissueArchive Portal (DNTP) to utilize PALGA’s nationwide network for requesting FFPE tissue samples. The DNTP consists of (1) a centrally organized internet portal to improve the assessing, processing, harmonization, and monitoring of the procurement process, while (2) dedicated HUB-employees provide practical support at peripheral pathology departments. Since incorporation of the DNTP, both the number of filed requests for FFPE tissue samples and the amount of HUB-mediated support increased 55 and 29% respectively. In line, the sample procurement duration time decreased significantly (− 47%). These findings indicate that implementation of the DNTP improved the frequency, efficiency, and transparency of FFPE tissue sample procurement for research in the Netherlands. To conclude, the need for biological resources is growing persistently to enable precision medicine. Here, we access PALGA’s national, pathology network by implementation of the DNTP to allow for efficient, consistent, and transparent exchange of FFPE tissue samples for research across the Netherlands.

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Quantification of HIV DNA in the brain by PCR: differences between fresh frozen and formalin fixed tissue.

Journal of Clinical Pathology ◽

10.1136/jcp.49.5.425 ◽

1996 ◽

Vol 49 (5) ◽

pp. 425-427 ◽

Cited By ~ 5

Author(s):

F Davison ◽

S F An ◽

F Scaravilli

Keyword(s):

Fixed Tissue ◽

Formalin Fixed Tissue ◽

Hiv Dna ◽

Fresh Frozen ◽

The Brain ◽

Formalin Fixed

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IMMUNOHISTOCHEMICAL LOCALIZATION OF HUMAN CHORIONIC GONADOTROPIN

Journal of Experimental Medicine ◽

10.1084/jem.115.2.289 ◽

1962 ◽

Vol 115 (2) ◽

pp. 289-294 ◽

Cited By ~ 149

Author(s):

A. R. Midgley ◽

G. B. Pierce

Keyword(s):

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Hydatidiform Mole ◽

Immunohistochemical Localization ◽

Formalin Fixation ◽

Cell Of Origin ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Immunohistochemical Techniques ◽

Formalin Fixed

Through the use of immunohistochemical techniques, human chorionic gonadotropin has been localized to syncytiotrophoblastic cells of immature placenta, hydatidiform mole, chorioadenoma destruens, and choriocarcinoma. No gonadotropin has been detected in cytotrophoblast. Evidence is discussed which suggests that syncytiotrophoblast is the cell of origin of human chorionic gonadotropin. The observation that formalin fixation did not alter the ability of human chorionic gonadotropin to react with its specific antibody permitted the study of formalin-fixed paraffin-embedded tissues stored in the tissue collection. In addition, the excellence of histologic preparations following formalin fixation facilitated cytologic identification.

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Comparison of Heart Valve Circumference Examined Before and After 10% Formalin Fixation

Siriraj Medical Journal ◽

10.33192/smj.2021.62 ◽

2021 ◽

Vol 73 (7) ◽

pp. 478-484

Author(s):

Watcharit Anantakal ◽

◽

Somboon Thamtakerngkit ◽

Vijarn Vachirawongsakorn ◽

◽

...

Keyword(s):

Mitral Valve ◽

Aortic Valve ◽

Heart Valve ◽

Tricuspid Valve ◽

Heart Valves ◽

Formalin Fixation ◽

Pulmonic Valve ◽

Fresh State ◽

Before And After ◽

Formalin Fixed

Objective: To compare the heart valve circumference before and after 10% formalin fixation. Materials and Methods: The study analyzed 63 Thai human cadaveric hearts. Each heart valve circumference was separately measured in the fresh state by specifically designed equipment. After that, the hearts were fixed in 10% formalin for 3 days. Then each heart valve circumference was measured by the same equipment and by the thread and ruler technique. The results were analyzed using SPSS package to find the association between the heart valve circumference before and after formalin fixation. Results: This study showed that the average circumferences of the heart valve measured in the fresh state were 13.329 cm in the tricuspid valve, 10.617 cm in the mitral valve, 8.416 cm in the pulmonic valve, and 7.122 cm in the aortic valve. The average circumferences of the heart valve measured after 10% formalin fixation were 11.019 cm in the tricuspid valve, 8.714 cm in the mitral valve, 6.751 cm in the pulmonic valve, and 6.089 cm in the aortic valve. The average ratios of the heart valve circumference measured fresh and after 10% formalin fixation were 0.8267 in the tricuspid valve, 0.8235 in the mitral valve, 0.8050 in the pulmonic valve, and 0.8573 in the aortic valve. There were significant differences in the heart valve circumference between the fresh state and after formalin fixation (p < 0.001). Conclusion: This study revealed important information on the dimensional changes of all the formalin-fixed heart valves. We found that the heart valve shrank after formalin fixation, with the formalin-fixed hearts an estimated 0.8 times smaller than the fresh cadaveric hearts.

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