The determination of the reliability of mutational analysis (mitotic index) in the prog-nostication of GISTs’ risk of relapse
Gastrointestinal stromal tumors
The determination of the reliability of mutational analysis (mitotic index) in the prognostication of GISTs’ risk of relapse
Introduction
The treatment of Gastrointestinal stromal tumors (GISTs), a common mesenchymal tumors of the gastrointestinal tract is an aggressive, rare as well as difficult to treat (Sujendran, 2007) presents a medical nightmare to patients and medical practitioners alike. Neoplastic gastrointestinal stromal tumors appears to arise from various and otherwise common precursor cells that are responsible for the creation of the interstitial cells of Cajal in the conventional myenteric plexus (Nishida & Hirota,2000).It is worth noting that GISTs can affect any part of the gastrointestinal tract. They are however very common in the small intestines and the stomach most likely as a consequence of activated mutations (Demetri,Mehren, Antonescu et al.,2010).
Problem of statement
Gastrointestinal stromal tumors (GISTs) have been shown to span a very wide spectrum of malignancy (Royster, 2006).Whenever a GIST is extracted surgically (resected), the patient and the physicians have the urge of predicting whether the surgery was curative or if the GIST would reappear later. A general agreement exists that a whole R0 resection (which indicates clear margins) presents hope of curing primary GIST. If microscopic evidence of the GIST cells are left on the margins (as a consequence of an R1 resection), then chances of preventing a relapse are increased immensely. It is worth noting that an incomplete resection that leaves visible elements of GIST (R2 resection) is never curative. Gastrointestinal stromal tumors (GISTs) presents a variety of medical complications which are extremely difficult to treat and manage. The ability to determine the progression as well as come up with a correct prognosis of a medical condition or disease is key to its better management and treatment. The existing prognostication techniques for GISTs are not reliable. The prognostication of the risk of relapse is even harder. Mutational analysis is one of the prognostication techniques of determining GISTs’ risk of relapse.
Aim
The aim of this study is to intensively investigate the reliability of mutational analysis as a technique in the prognostication of GISTs’ risk of relapse.
Objectives
The objectives of this study are;
To analyze mutational analysis as a GISTs prognostication technique
To provide a comparative analysis of mutational analysis and other GISTs prognostication tools
To identify as well as evaluate the advantages that are associated with mutational analysis technique in the prognostication of GISTs
To propose a better way of improving the reliability of mutational analysis on the prognostication of GISTs.
Literature review
Extant literature has been dedicated to the prognostication of GISTs. Royster (2006) mentioned the use of mitotic count in the prognostication of GIST relapse.Demetri,Benjamin and Blanke (2007) mentioned that mutational testing can be used prior to adjuvant imatinib testing for GISTs whose risks range from intermediate to high. Cho et al (2006) found that the deletion of exon-11 were closely associated with poor prognosis of GISTs.In their study, a 25 percent of the patients who experienced exon-11 deletion were noted to develop liver metastases as compared to between 0-6 percent of other mutation categories. Other publications indicated poorer prognostic for individuals with KIT exon-11 deletion (Corless et al.,2004;Martin et al.,2005;Waldelmann et al.,2003).Yalcinkaya,Yerci and Koc (1997) discussed the use of prognostic factors such as proliferative index,cellulality,mitotic index, tumor size, hemorrhage, mucosal invasion, telomerase activity, presence of necrosis, site of tumor and histological pattern.
Research methodology
The research is to involve a review of 40 cases of gastrointestinal stromal tumor cases in which mitotic index was used in the prognosis of the disease. This is to be followed by a quantitative analysis and determination of the reliability of the mitotic index in the prognostication of GIST.
Data collection
The data is to be collected from both primary and secondary sources. The primary sources of data are patient files obtained from hospital facilities and organizations that have data on GISTs and sarcomas. Some of the data is to be collected using questionnaires administered to medical doctors handling GIST patients.
Data Analysis
The data is to be analyzed quantitatively in order to determine the level of confidence and reliability of mitotic index as a prognostic technique for GIST.
Reliability and validity
This study will demonstrate both validity and reliability in its methodology. This study will be consistent as pointed out by Maylor & Blackmon (2005).This is to ensure that there is objectivity,professionalism and reliability in the reserach process.
LimitationsThe limitations that are most likely to face this research are related to the strict privacy and ethical guidelines that would demand permission to be sort from various sources. Time would also be a limiting factor.
References
HYPERLINK “http://sarcomahelp.org/learning_center/GIST_prognosis.html” http://sarcomahelp.org/learning_center/GIST_prognosis.html Cho S, Kitadai Y, Yoshida S, Tanaka S, Yoshihara M, Yoshida K, Chayama K.,2006. Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach. Int J Oncol. 2006 Jun;28(6):1361-7. PMID: 16685437
Corless CL, McGreevey L, Town A, Schroeder A, Bainbridge T, Harrell P, Fletcher JA, Heinrich MC,2004.KIT gene deletions at the intron 10-exon 11 boundary in GI stromal tumors. J Mol Diagn. 2004 Nov;6(4):366-70. PMID: 15507676
Demetri GD, Benjamin RS, Blanke CD et al ,2007.NCCN Task force report: management of patients with gastrointestinal stromal tumor (GIST)—update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 5(Suppl 2):S1–S29
Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H, Corless CL, Debiec-Rychter M, DeMatteo RP, Ettinger DS, Fisher GA, Fletcher CD, Gronchi A, Hohenberger P, Hughes M, Joensuu H, Judson I, Le Cesne A, Maki RG, Morse M, Pappo AS, Pisters PW, Raut CP, Reichardt P, Tyler DS, Van den Abbeele AD, von Mehren M, Wayne JD, Zalcberg J; NCCN Task Force..2007.NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)–update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw. 2007 Jul;5 Suppl 2:S1-29; quiz S30.
Martin J, Poveda A, Llombart-Bosch A, Ramos R, Lopez-Guerrero JA, Garcia del Muro J, Maurel J, Calabuig S, Gutierrez A, Gonzalez de Sande JL, Martinez J, De Juan A, Lainez N, Losa F, Alija V, Escudero P, Casado A, Garcia P, Blanco R, Buesa JM,2005. Spanish Group for Sarcoma Research. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol. 2005 Sep 1;23(25):6190-8.
Maylor, H., & Blackmon, K. ,2005. Researching Business and Management. Palgrave macmillan.
Nishida T, Hirota S.2000. Biological and clinical review of stromal tumours in the gastrointestinal tract. Histol Histopathol 2000;15:1293–301.
Royster,JD,2006. Prognosis in GIST
Sujendran, V., Fearnhead,N., De Pennington,N., Warren,B.F and Maynard,N.D .2007.
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Proposals for the management of gastrointestinal stromal tumours of the stomach
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Yalcinkaya U, Yerci O, Koc EU, 2007.Significance of p53 expression in gastrointestinal stromal tumors. Hepatogastroenterology. 2007 Jan-Feb;54(73):140-3.
Wardelmann E, Losen I, Hans V, Neidt I, Speidel N, Bierhoff E, Heinicke T, Pietsch T, Buttner R, Merkelbach-Bruse S. 2003. Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer. 2003 Oct 10;106(6):887-95.
