NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

The HOPE fixation technique--a promising alternative to common prostate cancer biobanking approaches.

Author(s): Braun M, Menon R, Nikolov P, Kirsten R, Petersen K, Schilling D, Schott C, Gündisch S, Fend F, Becker KF, Perner S

Publication: BMC Cancer, 2011, Vol. 11, Page 511

PubMed ID: 22151117 PubMed Review Paper? No

Purpose of Paper

The aim of this paper was to compare morphology and molecular endpoints among prostate specimens that were preserved by snap-freezing in liquid nitrogen, formalin-fixation and paraffin-embedding (FFPE), or hepes-glutamic acid buffer mediated organic solvent protection effect (HOPE) fixation and paraffin-embedding.

Conclusion of Paper

Case-matched FFPE and HOPE-fixed prostate specimens displayed comparable morphology, while freeze-induced artifacts and distorted morphology were reported for specimens snap frozen in liquid nitrogen. Immunohistochemical (IHC) staining was comparable among FFPE and HOPE-preserved specimens, while snap-frozen specimens displayed more prominent background staining. PCR amplification success was influenced by amplicon length and preservation method, with inferior results observed for FFPE specimens compared to snap-frozen or HOPE-fixed specimens. Quantitative RT-PCR (qRT-PCR) analysis revealed that differences in cycle threshold (Ct) values for three reference genes (TATA binding protein, TBP; glyceraldehyde 3-phosphate dehydrogenase, GAPDH; beta-actin) were significant among differentially preserved specimens (p<0.05), with the lowest values reported for snap-frozen specimens and the highest values for FFPE specimens. No significant differences in total protein yield, Western blot or fluorescence in situ hybridization (FISH) results were observed among differentially preserved specimens.

Studies

  1. Study Purpose

    The purpose of this study was to compare morphology and protein yield and integrity of ten case-matched surgically-resected prostate specimens preserved by snap-freezing in liquid nitrogen, FFPE, or HOPE fixation followed by paraffin embedding.

    Summary of Findings:

    Case-matched FFPE and HOPE-fixed prostate specimens displayed comparable morphology, while freeze-induced artifacts and distorted morphology were reported for specimens that were snap frozen in liquid nitrogen. IHC staining for prostate-specific antigen (PSA), Golgi phosphoprotein 2 (GOLPH2), and p63 was comparable between FFPE and HOPE-preserved specimens, although an antigen retrieval step was required for specimens preserved by FFPE but not HOPE. Snap-frozen specimens displayed more prominent background staining than FFPE or HOPE-fixed specimens. Total protein yields and Western blot analyses were comparable across differentially fixed specimens.

    Biospecimens
    Preservative Types
    • Frozen
    • Other Preservative
    • Formalin
    Diagnoses:
    • Neoplastic - Carcinoma
    • Neoplastic - Benign
    Platform:
    AnalyteTechnology Platform
    Morphology H-and-E microscopy
    Protein Immunohistochemistry
    Protein Western blot
    Protein Spectrophotometry
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Type of fixation/preservation Formalin (buffered)
    Snap frozen
    HOPE
    Immunohistochemistry Specific Targeted peptide/protein PSA
    GOLPH2
    p63
    Western blot Specific Targeted peptide/protein GOLPH2
    PSA
    Beta-actin
  2. Study Purpose

    The purpose of this study was to compare DNA and RNA integrity and suitability for molecular analysis of ten case-matched surgically-resected prostate specimens preserved by snap freezing in liquid nitrogen, FFPE, or HOPE fixation followed by paraffin embedding.

    Summary of Findings:

    PCR amplification success rates were influenced by preservation method and amplicon length. PCR analysis of 100-600 bp amplicons was successful for snap-frozen and HOPE-fixed, paraffin-embedded specimens, while PCR success was limited to 100-400 bp amplicons for FFPE specimens. qRT-PCR analysis of a six patient subset revealed that differences in Ct values for three reference genes (TBP, GAPDH, beta-actin) were significant among differentially preserved specimens (p<0.05). The magnitude of Ct differences was greatest between snap-frozen and FFPE specimens which had the lowest and highest mean values, respectively, and differed by 6, 8, and 10 cycles for TBP, GAPDH, and beta-actin, respectively. The magnitude of Ct differences was notably smaller between snap-frozen and HOPE-fixed specimens which differed by 1-2 cycles for each reference gene. FISH analysis of Ets related gene (ERG) was successful for all specimens, although proteinase pretreatment was required for HOPE-fixed specimens to enhance signal, and freeze-induced artifacts were observed among snap-frozen specimens.

    Biospecimens
    Preservative Types
    • Frozen
    • Other Preservative
    • Formalin
    Diagnoses:
    • Neoplastic - Carcinoma
    • Neoplastic - Benign
    Platform:
    AnalyteTechnology Platform
    DNA FISH
    DNA PCR
    RNA Spectrophotometry
    RNA Real-time qRT-PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Type of fixation/preservation Snap frozen
    Formalin (buffered)
    HOPE
    Real-time qRT-PCR Specific Targeted nucleic acid TBP
    GAPDH
    Beta-actin
    FISH Specific Targeted nucleic acid ERG
    PCR Specific Targeted nucleic acid TBXAS1
    RAG1
    PLZF
    AF4
    PCR Specific Length of gene fragment 100 bp
    200 bp
    300 bp
    400 bp
    600 bp

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