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

Analysis of DNA in fresh and fixed tissue by the polymerase chain reaction.

Author(s): Rogers BB, Alpert LC, Hine EA, Buffone GJ

Publication: Am J Pathol, 1990, Vol. 136, Page 541-8

PubMed ID: 2156429 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to evaluate the influence of tissue pretreatment (proteinase K, Triton X-100), specimen size, and formalin fixation duration (6 hours to 4 weeks) on the ability to amplify the c-K-ras gene from surgical and autopsy biospecimens using polymerase chain reaction (PCR).

Conclusion of Paper

The authors report formalin fixation decreased PCR efficiency in a time-dependent manner, with a significant decrease in amplicon intensity after 1 to 4 weeks in formalin compared to fresh frozen controls. PCR products were detectable in all formalin fixed biopsy specimens analyzed, but were absent in 2 of 6 formalin fixed autopsy specimens. Paraffin embedding, biospecimen size, and pretreatment with proteinase K or Triton X-100 did not significantly affect PCR amplification of the c-K-ras target gene.

Studies

  1. Study Purpose

    The purpose of this study was to determine if pretreatment of formalin-fixed, paraffin-embedded (FFPE) biopsy gastrointestinal specimens or the size of liver autopsy specimens impact the efficiency of PCR amplification of the c-K-ras gene.

    Summary of Findings:

    Tissue permeabilization with proteinase K or Triton X-100 (overnight at 48 degrees C) prior to DNA extraction did not significantly affect amplification of c-K-ras when compared to negative controls. While similar amplicon levels were observed among differing specimen sizes (assessed by proportions of a 5 um tissue section) fixed in formalin for 24 h, the generation of nonspecific products decreased with decreasing specimen size.

    Biospecimens
    Preservative Types
    • Formalin
    Diagnoses:
    • Neoplastic - Carcinoma
    • Not specified
    • Autopsy
    Platform:
    AnalyteTechnology Platform
    DNA PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Time in fixative 24 h
    Analyte Extraction and Purification Cell/tissue permeabilization No pretreatment
    Proteinase K
    Triton X-100
    Biospecimen Aliquots and Components Aliquot size/volume 1/6 of a tissue section
    Entire tissue section
    1/2 of a tissue section
    1/4 of a tissue section
  2. Study Purpose

    The purpose of this study was to determine if the duration of formalin fixation (6 h to 4 weeks) affects PCR amplification efficiency of c-K-ras.

    Summary of Findings:

    PCR amplification efficiency decreased in a fixation duration dependent manner. While the earliest decrease in amplicon intensity was observed in specimens fixed for 72 hours, a more robust and significant decrease was observed after fixation in formalin for 1 week or more (4 weeks). Paraffin embedding had no observable effect on PCR amplification.

    Biospecimens
    Preservative Types
    • Formalin
    Diagnoses:
    • Autopsy
    • Not specified
    • Neoplastic - Carcinoma
    Platform:
    AnalyteTechnology Platform
    DNA PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Time in fixative 6 h
    24 h
    72 h
    1 week
    2 weeks
    3 weeks
    4 weeks
    Biospecimen Preservation Embedding medium OCT
    Paraffin
  3. Study Purpose

    The purpose of this study was to determine if the method of biospecimen acquisition (biopsy versus autopsy) affects PCR amplification success of DNA extracted from FFPE tissue specimens. Liver, lung, heart, colon, and gastroitestinal tract specimens were included in the study.

    Summary of Findings:

    Of the 6 autopsy specimens assessed 2 failed to generate a c-K-ras amplicon, while all 39 biopsy specimens resulted in a detectable product. The duration of formalin fixation of these specimens was not specified.

    Biospecimens
    Preservative Types
    • Formalin
    Diagnoses:
    • Autopsy
    • Not specified
    • Neoplastic - Carcinoma
    Platform:
    AnalyteTechnology Platform
    DNA PCR
    DNA Southern blot
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Acquisition Method of tissue acquisition Autopsy
    Biopsy

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