Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit

Anne E. Rader, Anne Avery, Cecily L. Wait, Laura S. McGreevey, Douglas Faigel, Michael Heinrich

    Research output: Contribution to journalArticle

    106 Citations (Scopus)

    Abstract

    BACKGROUND. Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB. METHODS. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. RESULTS. Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case. CONCLUSIONS. Ancillary techniques such as immunocytochemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs.

    Original languageEnglish (US)
    Pages (from-to)269-275
    Number of pages7
    JournalCancer
    Volume93
    Issue number4
    DOIs
    StatePublished - Aug 25 2001

    Fingerprint

    Gastrointestinal Stromal Tumors
    Fine Needle Biopsy
    Immunohistochemistry
    Exons
    Polymerase Chain Reaction
    Mutation
    Endoscopic Ultrasound-Guided Fine Needle Aspiration
    Desmin
    Sequence Deletion
    Veterans
    Amino Acid Substitution
    Point Mutation
    Genes
    Smooth Muscle
    Gastrointestinal Tract
    Actins
    Neoplasms
    Coloring Agents
    DNA

    Keywords

    • Cytology
    • Fine-needle aspiration
    • Gastrointestinal stromal tumor
    • GIST

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit. / Rader, Anne E.; Avery, Anne; Wait, Cecily L.; McGreevey, Laura S.; Faigel, Douglas; Heinrich, Michael.

    In: Cancer, Vol. 93, No. 4, 25.08.2001, p. 269-275.

    Research output: Contribution to journalArticle

    Rader, Anne E. ; Avery, Anne ; Wait, Cecily L. ; McGreevey, Laura S. ; Faigel, Douglas ; Heinrich, Michael. / Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit. In: Cancer. 2001 ; Vol. 93, No. 4. pp. 269-275.
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    title = "Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit",
    abstract = "BACKGROUND. Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB. METHODS. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. RESULTS. Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case. CONCLUSIONS. Ancillary techniques such as immunocytochemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs.",
    keywords = "Cytology, Fine-needle aspiration, Gastrointestinal stromal tumor, GIST",
    author = "Rader, {Anne E.} and Anne Avery and Wait, {Cecily L.} and McGreevey, {Laura S.} and Douglas Faigel and Michael Heinrich",
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    T1 - Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit

    AU - Rader, Anne E.

    AU - Avery, Anne

    AU - Wait, Cecily L.

    AU - McGreevey, Laura S.

    AU - Faigel, Douglas

    AU - Heinrich, Michael

    PY - 2001/8/25

    Y1 - 2001/8/25

    N2 - BACKGROUND. Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB. METHODS. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. RESULTS. Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case. CONCLUSIONS. Ancillary techniques such as immunocytochemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs.

    AB - BACKGROUND. Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB. METHODS. Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. RESULTS. Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case. CONCLUSIONS. Ancillary techniques such as immunocytochemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs.

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    KW - Fine-needle aspiration

    KW - Gastrointestinal stromal tumor

    KW - GIST

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