The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%).
The cross validation SVM classifiers achieved with combination of stdDeviation, anatomic location and CD34_stain level demonstrated medium to good prediction efficiency (AUC = 0.864-0.904) regarding the GIST genotypes.
Gastrointestinal stromal tumor (GIST) is believed to originate from intestinal cells of Cajal or their stem cell precursors, and expresses stemness-related markers, such as CD117, CD34, DOG1 and nestin.
<i>Materials and methods</i> We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with <i>BCR-ABL</i>, and other tumors without <i>BCR-ABL</i> (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST).
After imatinib treatment, in both patients, the resected tumors were composed of heterogeneous spindle cells negative to KIT, DOG1, and CD34 IHC staining, which was unusual for GIST.
Immuhistochemical analysis of CD34 and CD117 was performed on GIST biopsy samples from both siblings, while c-kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin-embedded gastric biopsy specimens of affected siblings.
Additional transcripts relevant to GIST biology were also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and insulin receptor [INSR]), neural markers (CDH2[CDH: Cadherin], neurofilament, light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE like]), KIT, PDGFRA, CD34, and HIF1A.
Fine-needle aspiration biopsy revealed spindle cells with moderate pleomorphism and immunohistochemically reactive to CD117 and CD34 suggestive of GIST, but the clinical picture was unusual for GIST.
Compared with the overall mutation rate (8.7%) of exon 9, GISTs with CD34+SMA+ had > or = 20% probability of harboring an exon 9 mutation, and all GISTs in the small intestine had a probability of 19%.
The diagnosis of GISTs relies on histological arguments--proliferation of spindle-shaped cells in 70% of cases, of epithelioid cells in 20%, histological variants are rare--, and on immunohistochemical arguments--expression of CD117 in 95%, usually associated with CD34 expression in 70% of cases.
KIT-negative GISTs also showed lower expression rates of CD34, Bcl-2, and PKC than KIT-positive GISTs; mutational analysis revealed that 30% of KIT-negative GISTs harboured a PDGFRA exon 18 mutation.
This antibody yielded positive staining in 370 of 425 (87%) scorable GIST, whereas CD117 was positive in 317 of 428 (74%) GIST and CD34 in 254 of 430 (59%) GIST.
The findings confirmed the usefulness of CD117 and CD34 in diagnosing GIST and the prognostic role of MIB-1, but do not support a correlation between aneuploidy in flow cytometry and poor outcome.
Most GISTs (95%) express Kit (CD117), CD34 (70%), and heavy caldesmon (80%), whereas 25% are positive for smooth muscle actin and less than 5% for desmin.