title: Biological analysis of gastrointestinal stromal tumors.
abstract: The biological behaviour of a gastrointestinal stromal tumor (GIST) cannot be easily predicted from preoperative clinical examination alone. As a result, there is little standardization in the surgical treatment of GIST. In this study, we analyzed the clinicopathology and immunohistochemistry of 20 cases of GIST to clarify factors associated with tumors showing malignant potential. Immunohistochemical analysis of KIT, CD34, vimentin, alpha-smooth muscle actin (SMA), s-100, p53, ki-67, bcl-2 and bax expression was performed on 20 surgically resected GIST. An apoptotic index (AI) was calculated for each sample using a TdT-mediated dUTP-biotin nick end-labeling method. With regard to bcl-2, t(14;18) translocations were also investigated using a polymerase chain reaction based method. Finally, the relationship between these biological results and clinicopathological data was analyzed. Of the 20 cases studied, two patients died due to lung or liver metastasis. All cases stained positive for vimentin, nine cases were positive for alpha-SMA and three cases positive for s-100. All cases were stained for both KIT and CD34, which tended to correlate with malignant potential. There was significant difference in frequency of bcl-2 overexpression (p<0.05) and trend in Ki-67 labeling index (p=0.098) between benign and malignant cases. However, with regard to bcl-2, no chromosomal t(14;18) translocations were detected in four analyzed cases. In GIST, overexpression of bcl-2 may play an important role in increasing malignant potential. Furthermore, Ki-67 L.I. and bcl-2 overexpression may be useful in predicting malignant potential, and therefore help to determine the surgical treatment, follow-up manner, and the necessity of adjuvant therapy.
authors.affiliation: Department of Oncological Science (Surgery II), Oita Medical University, Hasama-machi, Oita, Japan. surg2@oita-med.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sato
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Takeno
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Uchida
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashima
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Wolfram
authors.initials: W
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011300:Preoperative Care; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D009418:S100 Proteins / Q000032:analysis; D017154:Stromal Cells / Q000737:chemistry* / Q000473:pathology; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014746:Vimentin / Q000032:analysis; D051028:bcl-2-Associated X Protein
chemical_list: D018952:Antigens, CD34; C494826:BAX protein, human; D014408:Biomarkers, Tumor; D017931:DNA Primers; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D014746:Vimentin; D051028:bcl-2-Associated X Protein; D019009:Proto-Oncogene Proteins c-kit