کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4135341 1271492 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors: markers with potential prognostic implications
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی آسیب‌شناسی و فناوری پزشکی
پیش نمایش صفحه اول مقاله
Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors: markers with potential prognostic implications
چکیده انگلیسی

SummaryGastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The prediction of the malignant potential of GISTs is still difficult. Altered cell cycle regulation may underlie the tumorigenesis and/or the progression of human malignancies. Although p53 and Bcl-2 have been extensively investigated in GISTs, little is known about the frequency of expression and possible clinical implications of alterations of other cell cycle regulatory proteins in these neoplasms. We have previously investigated the role of loss of p16INK4A by loss of heterozygosity and immunohistochemistry in the progression of GISTs and found that loss of heterozygosity of 9p and loss of p16 expression are confined to malignant GISTs. This has led us to investigate the role of other cell cycle regulatory proteins in these tumors. Twenty-three cases of GIST (9 low malignant potential [LMP], 10 primary malignant, and 4 intra-abdominal recurrences) were examined. All cases were strongly positive for KIT (CD117). Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G1-S transition and proteins that regulate apoptosis including Rb, E2F1, cyclin D1, CDK4, CDK6, p27KIP1, p21WAF1/CIP1, p53, Mdm2, Bcl-2, and Bax. The positive phenotypes identified were as follows: Rb, 39.1%; E2F1, 69.6%; cyclin D1, 30.4%; CDK4, 100%; CDK6, 30.4%; 39.1%; p27KIP1, 47.8%; p21WAF1/CIP1, 39.1%; p53, 43.5%; Mdm2, 17.4%; Bcl-2, 91.3%; and Bax, 100%. Malignant GISTs are more likely to be associated with a positive E2F1 and p53 phenotype and a negative p16 and p27KIP1 phenotype. It was concluded that aberration of the cell cycle regulators is a frequent finding and may be a contributing factor to the pathogenesis of GISTs. While some alterations are seen in LMP and malignant GISTs and therefore may represent an early event in molecular tumorigenesis of GISTs, other alterations are more common in malignant GISTs than LMP and therefore have potential utility as complementary tools for the prognostication of GISTs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Pathology - Volume 37, Issue 6, June 2006, Pages 648–655
نویسندگان
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