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

Real-time PCR analysis of RNA extracted from formalin-fixed and paraffin-embeded tissues: effects of the fixation on outcome reliability.

Author(s): Castiglione F, Degl'Innocenti DR, Taddei A, Garbini F, Buccoliero AM, Raspollini MR, Pepi M, Paglierani M, Asirelli G, Freschi G, Bechi P, Taddei GL

Publication: Appl Immunohistochem Mol Morphol, 2007, Vol. 15, Page 338-42

PubMed ID: 17721281 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to evaluate the effects of differing formalin fixation durations (1 to 72 h) on the amplification of GAPDH and COX-2 mRNAs using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR).

Conclusion of Paper

The authors report successful amplification of mRNA extracted from fresh (RNAlater preserved), formalin-fixed, and formalin-fixed, paraffin-embedded (FFPE) tissues for all fixation times examined; no effects of paraffin embedding were observed on RNA yield or amplification. Relative expression in formalin-fixed tissues was time-dependent, with samples fixed for 1 h displaying overexpression in 30% of samples, those fixed for 3 h displaying sample-dependent over- and under-expression, and those fixed for 24 to 72 h displaying overexpression in the majority of samples analyzed (75-87%) when compared to RNAlater preserved controls. Thus the authors conclude that qRT-PCR may be employed to compare mRNA levels between patients only if identical fixation times have been employed.

Studies

  1. Study Purpose

    The purpose of this study was to evaluate the effects of differing formalin fixation times (1 to 72 h) on the amplification of GAPDH and COX-2 mRNAs using qRT-PCR.

    Summary of Findings:

    The authors report successfully extracting RNA from fresh (RNAlater preserved) and formalin-fixed tissues, although RNA extracted from formalin-fixed tissue was more fragmented, 130-200 bp compared to 650 bp in RNAlater preserved controls. They also report successful amplification of mRNA extracted from fresh (RNAlater preserved), formalin-fixed, and formalin-fixed, paraffin-embedded (FFPE) tissues for all fixation times examined; no effects of paraffin embedding were observed on RNA yield or amplification. COX-2 was overexpressed in 30% of tissues formalin -fixed for 1 to 3 h compared to RNAlater preserved controls, and in 75-87% of tissue formalin-fixed for 24 to 72 h. Tissues fixed in formalin for 3 h also exhibited a mean underexpression compared to controls. Thus, the authors conclude that qRT-PCR may be employed to compare mRNA levels between patients only if identical fixation times have been employed.

    Biospecimens
    Preservative Types
    • Formalin
    • RNAlater
    Diagnoses:
    • Neoplastic - Normal Adjacent
    Platform:
    AnalyteTechnology Platform
    RNA Electrophoresis
    RNA Real-time qRT-PCR
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Preservation Type of fixation/preservation Formalin (buffered)
    RNAlater
    Biospecimen Preservation Time in fixative 1 h
    3 h
    24 h
    48 h
    72 h

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