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

PCR amplification of DNA from archival specimens. A methodological approach.

Author(s): Pavelic J, Gall-Troselj K, Bosnar MH, Kardum MM, Pavelic K

Publication: Neoplasma, 1996, Vol. 43, Page 75-81

PubMed ID: 8843966 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to determine the effects of fixation parameters, storage, and extraction procedures on PCR success.

Conclusion of Paper

A 318 bp fragment of beta-actin was successfully amplified in paraffin-embedded specimens fixed with AmeX, Carnoy's, 10% buffered formalin, paraformaldehyde or acetone, but not in Bouin's fixed specimens. Amplification was possible in unembedded specimens fixed with formalin for up to 48 h. Storage of formalin-fixed paraffin-embedded (FFPE) specimens for 10 years decreased PCR success. PCR amplification was only successful from FFPE specimens that were deparaffinized for more than 4 h, and there was no benefit of extracting the DNA with phenol-chloroform after proteinase k digestion. PCR was successful from Papanicolaou-stained cytological smears, but only after phenol-chloroform extraction.

Studies

  1. Study Purpose

    The purpose of this study was to determine the effects of fixative type on amplification of beta-globin from paraffin-embedded brain specimens.

    Summary of Findings:

    Amplification of a 318 bp fragment of beta-actin was successful in paraffin-embedded specimens fixed with AmeX, Carnoy's, or 10% buffered formalin. There was less amplification product from specimens fixed with paraformaldehyde or acetone, and PCR was not successful in specimens fixed with Bouin's fixative.

    Biospecimens
    Preservative Types
    • Formalin
    • Other Preservative
    Diagnoses:
    • Neoplastic - Benign
    • Neoplastic - Sarcoma
    • Normal
    • Autopsy
    Platform:
    AnalyteTechnology Platform
    DNA PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Type of fixation/preservation Paraformaldehyde
    Acetone
    AMeX
    Bouin's fixative
    Carnoy's solution
    Formalin (buffered)
  2. Study Purpose

    The purpose of this study was to determine the effects of fixation duration, storage, deparaffinization and extraction on the amplification of beta-globin from FFPE brain specimens.

    Summary of Findings:

    Beta-actin was successfully amplified from unembedded specimens fixed for up to 48 h, but there was a lower product yield when specimens were fixed for 48 h than when fixed for 24 h or less. Amplification of a 720 bp fragment of bcl-2 was successful after 40 cycles in FFPE specimens stored for 1 year, but not in specimens stored for 10 or 39 years. Increasing the number of PCR cycles to 50, allowed for amplification of bcl-2 from 10 year old specimens but not from 39 year old specimens. Beta-actin could be amplified when FFPE specimens were deparaffinized for more than 4 h, but not in specimens deparaffinized for less than 4 h. There was no benefit of extracting the DNA with phenol-chloroform after proteinase k digestion.

    Biospecimens
    Preservative Types
    • Formalin
    Diagnoses:
    • Neoplastic - Benign
    • Neoplastic - Sarcoma
    • Normal
    • Autopsy
    Platform:
    AnalyteTechnology Platform
    DNA PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Time in fixative 2 h
    4 h
    6 h
    8 h
    12 h
    24 h
    48 h
    Biospecimen Preservation Embedding medium Not embedded
    Paraffin
    Analyte Extraction and Purification Deparaffinization Xylene
    1 h
    2 h
    4 h
    24 h
    Analyte Extraction and Purification Protein digestion Proteinase k
    3 h
    4 days
    Analyte Extraction and Purification Analyte isolation method Phenol-chloroform extraction
    None
    PCR Specific Length of gene fragment 318 bp
    720 bp
    PCR Specific Targeted nucleic acid Beta-actin
    Bcl-2
    PCR Specific Number of cycles 30 cycles
    40 cycles
    50 cycles
    Storage Storage duration 1 year
    10 years
    39 years
  3. Study Purpose

    The purpose of this study was to determine the effect of Papanicolaou staining on the amplification of beta-actin and TGF-beta from cytological smears.

    Summary of Findings:

    Amplification of TGF-beta and beta-actin was only possible from Papanicolaou stained specimens after phenol-chloroform extraction. The authors report that eosin dye migrated through the gel producing an interfering fluorescent signal.

    Biospecimens
    Preservative Types
    • Ethanol
    Diagnoses:
    • Not specified
    Platform:
    AnalyteTechnology Platform
    DNA PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Analyte Extraction and Purification Analyte isolation method Phenol-chloroform extraction
    None
    PCR Specific Length of gene fragment 318 bp
    500 bp
    PCR Specific Targeted nucleic acid Beta-actin
    TGF-beta
    PCR Specific Type of tissue stain Papanicolaou stain

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