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

Rader, Anne E.; Avery, Anne K.; Wait, L B S Cecily; McGreevey, S B S Laura; Faigel, Douglas O.; Heinrich, Michael C.

doi:10.1002/cncr.9041

Cited by 116 publications

(94 citation statements)

References 44 publications

(30 reference statements)

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“…There is a proportion (5%) of true GISTs which are CD117 negative and antigen retrieval may result in false CD117 staining. In these cases the mutational analysis plays an important role in discovering mutations involving c-kit and PDGFRA genes, because it can confirm the diagnosis of GIST, if doubtful (12,13). In addition, mutational analysis has predictive value for sensitivity to imatinib therapy and prognostic implications (8).…”

Section: Discussionmentioning

confidence: 99%

Results on prognostic value of mutations in localized gastrointestinal stromal tumors (GIST): in one single center

Garcés-Albir

Martí-Obiol

López-Mozos

et al. 2012

Rev. esp. enferm. dig.

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Introduction: to study the prognostic value of mutations in KIT or PDGFRA in gastrointestinal stromal tumors (GIST) managed in our department.Materials and methods: forty five patients with localized GIST underwent surgery between 1998 and 2010. Thirty six patients were enrolled in a retrospective study. DNA was isolated from 3 to 5 µm sections of fixed and paraffin-embedded tissue. Exon 9, 11, 13 and 17 of c-kit gene and exon 12 and 18 of PDGFRA were amplified by PCR and sequenced.Results: tumors with mutations were larger at the surgery and showed higher mitotic count (p < 0.05). The mutations were found in 22 patients (61.2%), 18 had mutations in exon 11 of c-kit gene. PDGFRA mutations were located in exon 12. The 5-years relapsefree survival rate for patients with tumors having mutations was 38% and 100% for patients without mutations (p < 0.01). The 5-year survival rate was significantly worse for patients with mutations (20 vs. 97%, p < 0.01), with tumors larger than 5 cm (28 vs. 97%, p < 0.01) and with > 50 mitosis/HPF (42 vs. 88%, p < 0.03). Multivariate analyses indicated that the mutations, mitotic counts, and tumor size were independent prognostic factors for survival in patients with localized GIST.Conclusions: in this series, having a detected mutation is a poor prognostic factor with significantly increased recurrence rate and shortens survival. Key words:Gastrointestinal stromal tumors (GIST). c-kit. PDGFRA. Mutation. ABBREVIATIONSPDGFRA: platelet-derived growth factor receptor alpha. GIST: gastrointestinal stromal tumor. PCR: polymerase chain reaction. HPF: high power fields. PET: positron emission tomography. INTRODUCTIONGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are defined here as c-kit or KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasm primary in the GI tract, omentum, mesentery or retroperitoneum (1).Although around 87% of GIST expressed KIT, only 57-92% (according to the series and the diagnostic techniques) of GISTs showed mutations juxtamembrane to the c-kit gene domain (2-5).The c-kit mutations are mainly located in the exons 9, 11, 13 and 17. The frequencies of the mutations are 75-80% for the exon 11 and 20% for the exon 9. Also we found mutations in another receptor, PDGFRA, principally in the exons 12 and 18 (6). An important characteristic in the molecular pathology of these tumors are that the c-kit and PDGFRA mutations are reciprocally excluded (7,8).There is a group of GIST (approximately 2-10% of cases) that expresses very weakly or do not express c-kit, but in 10-50% of the cases they present c-kit or PDGFRA mutations and this helps to confirm the diagnosis of GIST (7). Vol. 104. N.° 8, pp. 405-410, 2012 Some of these results were presented in a session of the XXVIII Annual National Congress of the Spanish Society of Surgeons, held in Madrid (November, 2010 Results on prognostic value of mutations in localized gastrointestinal stromal tumors (GIST) in on...

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Section: Discussionmentioning

confidence: 99%

Results on prognostic value of mutations in localized gastrointestinal stromal tumors (GIST): in one single center

Garcés-Albir

Martí-Obiol

López-Mozos

et al. 2012

Rev. esp. enferm. dig.

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“…Although the tumor amount of cell blocks prepared from fine needle aspirations obtained from the lung, pancreas, gastrointestinal tract, soft tissue masses, and similar tissues is very small, clearly successful results are obtained (1,18,29,31,32,85,93,94).…”

Section: Methods Of Cytopreparationmentioning

confidence: 99%

“…However, it should be noted that the tumor cell ratio can be low in cell blocks even if the total amount of material is high. Tumor enrichment such as microdissection can be applied to cell blocks as for tissue blocks (15).Although the tumor amount of cell blocks prepared from fine needle aspirations obtained from the lung, pancreas, gastrointestinal tract, soft tissue masses, and similar tissues is very small, clearly successful results are obtained (1,18,29,31,32,85,93,94).Cell blocks have similar advantages to liquid-based samples. However, a common disadvantage in both the cell block and the liquid-based specimen is that material adequacy cannot be determined immediately.…”

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confidence: 99%

Techniques for maximizing the performance of molecular pathology testing: responsibilities of all pathologists

Uzun

Sarıoğlu²

2017

TJPATH

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Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities.This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs) and cell-free circulating nucleic acids), effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned.Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.Key Words: Molecular Pathology, Tissue saving, Tumor enrichment, Tumor percentage INTRODUCTION "Molecular Pathology" is one of the pathological methods with expanding role in patient diagnosis, prediction of prognosis and treatment. Tissue and cellular material from patients have always been valued in pathology laboratories; however they gain additional importance in the molecular pathology era with the increase in new disease classifications according to molecular changes and new targeted therapy options being determined with predictive molecular testing.While the value of diseased and normal tissue is expanding with the advances in immunohistochemistry and molecular pathology, minimally invasive techniques have taken the place of radical processes in tissue sampling along with developments in the technology. These techniques are better for the comfort of the patient but they also have disadvantages, as they provide smaller amounts of tissue for diagnosis. The management of tissues obtained with these techniques can be problematic for pathologists. The application of individualized treatment regimens developed in recent years has depended on molecular studies. The adequacy of the obtained material and its reliability for molecular investigation are of utmost importance in many cases.The diagnosis of lung carcinomas is usually made with small biopsies or cytological materials and these materials are generally the only options for further studies. Transthoracic, transbronchial fine needle aspirations, forceps biopsies, bronchial brushes, and washes are some of these materials (1). A molecular examination requires the best process and good sample quality. The most important factor for the success of molecular tests is the number of tumor cells and the percentage of mutant cells (2). The requirements for tumor cell number and mutation perc...

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“…EGFR exons 18, 19, 20, and 21 were amplified using the following primer pairs: 5 ¶-GCTGAG-GTGACCCTTGTCTC-3 ¶ (EGFR sense primer, exon 18), . PCR amplification of genomic DNA was performed using 500 ng of DNA (38).…”

Section: Methodsmentioning

confidence: 99%

“…Samples were run at 50jC (EGFR, exons 19 and 20) to check for length mutations or at 62jC for EGFR exon 18, 59.4jC for EGFR exon 19, 63jC for EGFR exon 21, 58.1jC for KRAS exon 1, 58.5jC for KRAS exon 2, 55.4jC for PIK3CA exon 9, and 57.5jC for PIK3CA exon 20 for the screening for point mutations. In addition, amplimers were bi-directionally sequenced on an ABI 310 sequencer using the BigDye terminator kit (38).…”

Section: Denaturing Wave High Per Formanc E Liquid Chromatographymentioning

confidence: 99%

Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

Schittenhelm

Kollmannsberger

Oechsle

et al. 2009

Molecular Cancer Therapeutics

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Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be effective in patients with nonsmall cell lung cancer (NSCLC) that express EGFR. We recently published a phase I study of weekly matuzumab plus paclitaxel. This therapy was well tolerated and showed clinical responses in the majority of patients. Although matuzumab displays potent antitumor activity in some patients, not all patients respond well to treatment. Whether dysregulation of EGFR-mediated pathways precludes or sensitizes cells to paclitaxel is unknown. We sought to determine molecular predictive factors for therapy response in a phase

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

Cited by 116 publications

References 44 publications

Results on prognostic value of mutations in localized gastrointestinal stromal tumors (GIST): in one single center

Results on prognostic value of mutations in localized gastrointestinal stromal tumors (GIST): in one single center

Techniques for maximizing the performance of molecular pathology testing: responsibilities of all pathologists

Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer

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