GISTs with predominant epithelioid cell morphology may pose a diagnostic dilemma therefore in all suspected cases of GIST, immunocytochemistry for c-Kit and/or DOG1 should be employed on cell block preparations to confirm the diagnosis of GIST.
The nodule was resected in an enucleation procedure; subsequent histopathologic examination revealed a low-grade, spindled cell neoplasm with diffuse immunoreactivity for CD117 (cKit) and DOG1, diagnostic of GIST.
TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer.
Before anoctamins (TMEM16 proteins) were identified as a family of Ca<sup>2+</sup>-activated chloride channels and phospholipid scramblases, the founding member anoctamin 1 (ANO1, TMEM16A) was known as DOG1, a marker protein for gastrointestinal stromal tumors (GIST).
Twenty years after the discovery of KIT in GISTs, the diagnosis of GISTs became much more accurate by using immunohistochemical (IHC) panel (CD117/DOG1) and molecular analysis (<i>KIT/PDGFRA</i>), both of which constitute the gold standard of diagnosis in GISTs.
Dedifferentiation in GIST is a rare histologic change which may occur de novo or secondary to imatinib therapy and is characterized by abrupt transition of well-differentiated (WD) GIST to a subclonal anaplastic process that shows loss of immunohistochemical marks (CD117, DOG1).
Pathologically, diagnosis of a GIST relies on morphology and immunohistochemistry [KIT and/or discovered on gastrointestinal stromal tumor 1 (DOG1) is generally positive].
Immunohistochemical examination was performed with primary antibodies to CD34, CD117, SMA, and vimentin, and TMEM16a (DOG-1), the latter was used for the diagnosis of gastrointestinal stromal tumours (GIST) consisting of TCs.
SDH-deficient gastrointestinal stromal tumours (GISTs) show distinctive features, including absent KIT proto-oncogene receptor tyrosine kinase/platelet-derived growth factor receptor A (KIT/PDGFRA) mutations [but positive staining for cKIT and DOG1], virtually exclusive gastric location, lobulated growth, multi-focality, a prognosis not predicted by size and mitotic rate, frequent metastasis to lymph nodes and primary resistance to imatinib therapy.
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.
However, its function as a calcium-activated chloride channel suggests that the expression of ANO1 is not restricted to gastrointestinal stromal tumors.
Furthermore, immunohistochemistry with CD117, DOG1, and other molecular markers is critical for diagnosis of GIST of the stomach and facilitates optimization of treatments for GIST.
Typically, IHC staining for v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene (KIT) and discovered on GIST-1(DOG1) is positive in almost all GISTs.
By means of immunohistochemical analysis, all GIST cells expressed CD117, CD34 and Dog1 in all six synchronous gastric adenocarcinomas with GIST, and in GIST alone.
Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis.