DNA ploidy andc-Kitmutation in gastrointestinal stromal tumors

Abstract

AIM:To investigate the prognostic significance of c-Kit gene mutation and DNA ploidy in gastointestinal stromal tumors (GISTs). METHODS:A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC) techniques. DNA ploidy was determined by flow cytometry. RESULTS:Of the 55 cases of GISTs, 53 cases (96.4%) expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%), respectively. No mutations were found in exons 13 and 17. DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type. There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs. CONCLUSION:DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.Lee JH, Zhang X, Jung WY, Chae YS, Park JJ, Kim I. DNA ploidy and c-Kit mutation in gastrointestinal stromal tumors.

Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience

“…[ 4 ] The primary double KIT mutations which are quite rare may involve nucleotides within the same hotspot exon, which is considered to have an origin in a single mutagenic event or is characterized by losses or frameshift/stop codon mutations in the wild-type KIT allele of KIT -mutated GISTs. [ 23 ] Only 4 examples of double primary mutations involving different hotspot exons of KIT in treatment-naive GISTs are available in literature till date, of which 3 involved exons 9 and 11,[ 24 25 ] one in exons 13 and 17. [ 26 ] A novel occurrence of primary double mutation in exons 11 and 13, in a therapy-naive patient with gastric GIST was reported in this study.…”

Prediction of aggressiveness of gastrointestinal stromal tumours based on immunostaining with bcl‐2, Ki‐67 and p53

“…[4][5][6][7][8][9][10][11][12][13]25,26,[28][29][30][31][32][33] Among these assays, immunohistochemical evaluation of biomarker expression, perhaps, is the most common approach for predicting the aggressiveness of GISTs. [4][5][6][7][8][9][10][11][12][13]25,26,[28][29][30][31][32][33] Among these assays, immunohistochemical evaluation of biomarker expression, perhaps, is the most common approach for predicting the aggressiveness of GISTs.…”

“…Because of the relative insensitivity of histopathological features in predicting the biologic behaviour of GIST, many investigators have attempted to identify better predictive parameters which include biomarker expression, mutational analysis of c-kit, DNA ploidy and image analysis using histological materials. [4][5][6][7][8][9][10][11][12][13]25,26,[28][29][30][31][32][33] Among these assays, immunohistochemical evaluation of biomarker expression, perhaps, is the most common approach for predicting the aggressiveness of GISTs. Ki-67 is the most frequently studied marker.…”

KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)

“…16,54 The presence of two different KIT or PDGFRA mutations affecting the same or different exons has been reported in a few cases. 42,[55][56][57][58] More recently, double KIT exon 11 mutations have been found in as many as 9% (7 of 78) of primary tumors in 1 study. 59 Also, coexistence of missense and silent KIT exon 11 mutations and missense and nonsense KIT exon 11 mutations was reported twice in the primary tumors.…”