Gastrointestinal Stromal Tumor: Genotype Frequency and Prognostic Relevance.
BACKGROUND
Genotyping has an important role in the prognosis and prediction of response to tyrosine kinase inhibitor therapy. KIT exon 11 deletions serve as an adverse prognostic marker. Gastrointestinal stromal tumor (GIST) genotype has been described in developed countries; however, data from India are lacking. The aim of this study was to determine the genotype frequency and its prognostic relevance.


METHODS
Eighty consecutive cases of resected GIST were evaluated for histologic and immunohistochemical findings. Mutation analysis for exons 9, 11, 13, and 17 of KIT and 12 and 18 of PDGFRA was carried out by PCR-Sanger sequencing. Genotypes were correlated with risk groups, recurrence, and imatinib therapy.


RESULTS
Forty-seven of 80 cases (58.7%) showed mutations, including 30 cases (37.5%) in KIT exon 11, 9 cases (11.2%) in KIT exon 9, and 8 cases (10%) in PDGFRA exon 18. Codon 557-558 deletion was present in 15 cases. D842E was the most common in PDGFRA, with similar histologic features as D842V. KIT exon 11 deletion had higher mitotic rate, larger tumor size, high-risk stratification, and lower recurrence-free survival. Recurrences were seen in 12 (16.4%) patients. Nine patients (75%) with recurrence were on imatinib therapy.


CONCLUSIONS
GIST genotype frequency is lower in Indians. KIT exon 11 deletion is associated with poor prognosis compared with wild-type and other missense mutations. D842E is a common PDGFRA mutation in Indian patients. Patients with a wild genotype are not suitable candidates for imatinib therapy. Genotyping can serve as an important prognostic marker.
Departments of Pathology.
Niraj
N
Kumari
Departments of Pathology.
Valli
V
Priyaa
Departments of Pathology.
Pooja
P
Shukla
Surgical Gastroenterology.
Ashok
A
Kumar
Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Rakesh
R
Aggarwal
Departments of Pathology.
Narendra
N
Krishnani
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047368:Tumor Burden