Evidence map›Paper›PMID 21679412›Full record

ArticleBMC cancer2011

Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens.

Al Muktafi Sadi, Dong-Yu Wang, Bruce J Youngson, Naomi Miller, Scott Boerner, Susan J Done, Wey L Leong

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 37 citations in OpenAlex.

  1. Pooled it
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  3. Expression profiling of archival tumors for long-term health studies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012
    Pooled it
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  8. ANLN Regulated by miR-30a-5p Mediates Malignant Progression of Lung Adenocarcinoma.Computational and mathematical methods in medicine · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Al Muktafi SadiOntario Cancer Institute and Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.
Dong-Yu Wang
Bruce J Youngson
Naomi Miller
Scott Boerner
Susan J Done
Wey L Leong
Ontario Institute for Cancer Research · CAUniversity Health Network · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe ability of gene profiling to predict treatment response and prognosis in breast cancers has been demonstrated in many studies using DNA microarray analyses on RNA from fresh frozen tumor specimens. In certain clinical and research situations, performing such analyses on archival formalin fixed paraffin-embedded (FFPE) surgical specimens would be advantageous as large libraries of such specimens with long-term follow-up data are widely available. However, FFPE tissue processing can cause fragmentation and chemical modifications of the RNA. A number of recent technical advances have been reported to overcome these issues. Our current study evaluates whether or not the technology is ready for clinical applications.

methodsA modified RNA extraction method and a recent DNA microarray technique, cDNA-mediated annealing, selection, extension and ligation (DASL, Illumina Inc) were evaluated. The gene profiles generated from FFPE specimens were compared to those obtained from paired fresh fine needle aspiration biopsies (FNAB) of 25 breast cancers of different clinical subtypes (based on ER and Her2/neu status). Selected RNA levels were validated using RT-qPCR, and two public databases were used to demonstrate the prognostic significance of the gene profiles generated from FFPE specimens.

resultsCompared to FNAB, RNA isolated from FFPE samples was relatively more degraded, nonetheless, over 80% of the RNA samples were deemed suitable for subsequent DASL assay. Despite a higher noise level, a set of genes from FFPE specimens correlated very well with the gene profiles obtained from FNAB, and could differentiate breast cancer subtypes. Expression levels of these genes were validated using RT-qPCR. Finally, for the first time we correlated gene expression profiles from FFPE samples to survival using two independent microarray databases. Specifically, over-expression of ANLN and KIF2C, and under-expression of MAPT strongly correlated with poor outcomes in breast cancer patients.

conclusionWe demonstrated that FFPE specimens retained important prognostic information that could be identified using a recent gene profiling technology. Our study supports the use of FFPE specimens for the development and refinement of prognostic gene signatures for breast cancer. Clinical applications of such prognostic gene profiles await future large-scale validation studies.

Indexed as

FormaldehydeOligonucleotide Array Sequence AnalysisParaffin EmbeddingTissue FixationAdultAgedBiomarkers, TumorBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedPrognosisReceptors, EstrogenBiomarkers, TumorErb-b2 Receptor Tyrosine KinasesFormaldehydeReceptors, Estrogen

Identifiers

PMID21679412
PMCPMC3128009
OpenAlexW2022993352

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.