BACKGROUND Oncocytic neoplasms of the salivary glands are rare and the differential diagnosis between oncocytic carcinomas (OCs) and oncocytomas is difficult. We present 5 cases of oncocytoma and 3 cases of OC of the salivary glands with clinicopathological and immunohistochemical comparisons. METHODS Eight cases of oncocytic neoplasms diagnosed at Asan Medical Center between 1998 and 2009 were reviewed for clinical data and histological features. Immunohistochemical staining for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her-2), c-kit, p53, and Ki-67 was done. RESULTS Cytological differences between oncocytomas and OCs were not obvious, but unequivocal infiltrative growths were identified in 3 cases, rendering the diagnosis of oncocytic carcinoma. When the remaining cases were classified as oncocytomas, there was no difference in age, size, and clinical symptoms between oncocytomas and OCs. Two of 3 OCs showed strong membranous expression of c-kit, but all oncocytomas were negative. The proportion of p53-positive cells was larger in OCs than oncocytomas. Her-2 or EGFR expression was absent, and Ki-67 labeling indices were less than 1% in all cases. CONCLUSIONS An infiltrative growth pattern, strong membranous expression of c-kit, and an increased proportion of p53-positive cells are features that can differentiate OCs from oncocytomas of the salivary glands.
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Primary oncocytic carcinoma of ectopic salivary gland: a unique case E. Touli, A. Manganaris, C. Nikolaidou, I. Karasmanis International Journal of Oral and Maxillofacial Surgery.2022; 51(4): 463. CrossRef
BACKGROUND Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis. METHODS We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues. RESULTS Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11. CONCLUSIONS Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.
BACKGROUND KIT and PDGFRA are tyrosine kinase receptors.
Stem cell factor/KIT-mediated signaling plays a role in normal spermatogenesis, and the alteration of KIT is important in the pathogenesis of seminomas/dysgerminomas (SD). METHODS: To determine the role of expression and mutation of the KIT and PDGFRA genes, we analyzed 16 seminoma cases, 4 spermatocytic seminoma (SS) cases and 8 dysgerminoma cases for KIT and PDGFRA expression and mutation of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR-SSCP methods. RESULTS: KIT was immunohistochemically positive in all 24 SD cases, and one of four (25%) SS cases. PDGFRA was immunohistochemically evident in 16 of the 24 (66.6%) SD cases, and two of the four (50%) SS cases. KIT expression was significantly reduced in SS compared with seminoma (p=0.0035). Four cases (14.3%) displayed mutation in KIT exon 17 or PDGFRA exon 12.
Distant metastasis was present in three cases (10.7%), one of which had a nonsense mutation in KIT. CONCLUSIONS: These results indicate that KIT is expressed in the majority of SD cases, but not in most SS cases. However, there was no significant correlation between the clinicopathologic features and mutation or expression of KIT and PDGFRA.
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Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors Sung Hee Jung, Kwang Sun Suh, Dae Young Kang, Dong Wook Kang, Young-Beum Kim, Eun-Sun Kim Gut and Liver.2011; 5(2): 171. CrossRef
Colonic gastrointestinal stromal tumors (GISTs) are rare and behave aggressively compared to GISTs in other parts of the gastrointestinal tract. Therefore, accurate diagnosis of GISTs and their distinction from other mesenchymal tumors is important for proper patient management and follow-up.
Herein, we present an unusual case of a colonic GIST mimicking an inflammatory fibroid polyp with a novel 63 bp deletion mutation in exon 11 of the c-kit gene, which has not previously been reported. The tumor consisted of loosely arranged spindle cells and many inflammatory cells scattered throughout the tumor. Immunohistochemically, the tumor cells were focally and weakly positive for c-kit and diffusely positive for CD34, but were negative for PKC-theta, SMA, S-100 protein, ALK-1, and desmin. Our case re-emphasizes the broad morphologic spectrum of GISTs.
Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g.
The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields.
Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.
BACKGROUND The interstitial cell of Cajal (ICC), the cell of origin for gastrointestinal stromal tumor (GIST), expresses CD117 (c-kit) which is a receptor for KIT ligand in cell membranes. It is immunohistochemically positive for CD117, CD34 and vimentin, but not for alpha-smooth muscle actin (SMA). METHODS We performed the immunohistochmical study with anti-CD117, anti-CD34, anti-VMT and anti-alpha-SMA in paraffin-embedded tissue of 28 GISTs and 19 smooth muscle tumors arising in the gastrointestinal tract, mesentery, omentum and retroperitoneum (GISMT) to determine the precise nature of GIST cells. RESULTS The positive rates of CD117, CD34 and vimentin in extraGISTs were significantly higher than in GISMTs. The positive rate of alpha-SMA in GIST was not significantly different than in GISMTs. CONCLUSIONS A subset of GISTs may express alpha-SMA as well as CD117 and the cell of their origin may be a ICC precursor cell which is capable of differentiating bidirectionally into ICC and smooth muscle cell. This explains why GISTs may arise out of gut where ICC is not present and that they may represent the tumors arising from ICC precursor cell present around the gastrointestinal tract.
BACKGROUND The proto-oncogene c-kit encodes a transmembrane tyrosine kinase growth factor receptor.
Studies have shown that c-kit is highly expressed in normal breast epithelium, but expression is decreased in primary breast cancer. Cyclooxygenase-2 (COX-2) is an inducible enzyme that converts arachidonic acid to prostaglandins.
Expression of COX-2 has been reported in malignant tumors including breast cancer. We evaluated the expression of c-kit and COX-2 in benign and malignant lesions of the breast to assess the roles of these proteins in cancer initiation and progression. METHODS We characterized 20 benign lesions, 20 intraductal carcinomas and 70 invasive breast carcinomas.
Immunohistochemical staining for c-kit and COX-2 was performed. RESULTS Expression of c-kit was detected in 75% of the benign breast lesions, 40% of the intraductal carcinomas and 10% of the invasive carcinomas. COX-2 expression was observed in 80% of the benign lesions, 70% of the intraductal carcinomas and 52% of the invasive carcinomas.
Expression of c-kit was significantly correlated with tumor size (p=0.02). COX-2 expression was significantly correlated with negative expression of estrogen receptor and progesterone receptor (p=0.02, p=0.04), Her-2/neu expression (p=0.008) and the high proliferation index (p=0.0002). CONCLUSIONS Our results suggest that c-kit and COX-2 might be involved in malignant transformation of the mammary epithelium and tumor progression. It is suggested that c-kit and COX-2 can be used as predictive markers and therapeutic targets.
BACKGROUND The abnormal expression of c-kit is implicated in the pathogenesis of a variety of solid tumors. The Rb pathway and p53 act as cell cycle regulators. The purpose of this study was to assess the expression of c-kit, Rb, p53, p16 and cyclin D1 and their relationship to clinical and pathological parameters in patients with non-small cell lung carcinomas (NSCLC(s)). METHODS Tissue microarrays consisting of 2 mm cores from the corresponding blocks were constructed from 54 NSCLC(s).
Immunohistochemical staining for c-kit, Rb, p53, p16 and cyclin D1 was performed. C-kit immunostaining was considered positive if > or =10% of tumor cells were immunoreactive along the membrane and/or in cytoplasm. For Rb, p53, p16 and cyclin D1, tumor cells showing a nuclear staining pattern were interpreted as positive. RESULTS We found that c-kit was expressed in 13 (24%) cases, Rb was lost in 39 (72%) cases, p53 was expressed in 28 (52%) cases, p16 was lost in 42 (78%) cases and cyclin D1 was expressed in 33 (61%) cases. The c-kit expression was significantly higher in adenocarcinoma (39%) than in squamous cell carcinoma (8%). We did not find any correlation between c-kit, Rb, p53, p16 and cyclin D1 expression and clinicopathological parameters such as: age, tumor size, lymph node involvement, disease stage and distant metastasis. There was a direct correlation between p53 expression and Rb loss. CONCLUSIONS These results suggest that c-kit may be a useful therapeutic target for patients with c-kit positive tumors, and that the disruption of Rb and p53 pathways may play an important role in the development and progression of NSCLC(s).
Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract, but this tumor is rarely seen in association with type 1 neurofibromatosis (NF-1). We report here on two cases of multiple GISTs of the small intestine that occurred in NF-1 patients. We also analyzed the mutations of c-kit exons 9, 11, 13 and 17 and the plateletderived growth factor receptor-alpha (PDGFRA) exons 12 and 18 in two GIST patients. Histologically, the NF-1-associated GISTs were similar to those of non-the NF-1 GISTs, but they characteristically revealed hyperplastic interstitial cells of Cajal around the GISTs. Immunohistochemically, these tumors showed strong co-expressions of CD117 and CD34. The molecular genetic analysis of the GISTs showed that all of the c-kit and PDGFRA exons that were analyzed in the GISTs of the two patients were the wild-type, suggesting a limited role for the c-kit and PDGFRA mutations in the tumorigenesis of NF-1-associated GISTs.
BACKGROUND Our objectives in this study were to (1) evaluate the possible role of p53, c-kit and CD34 proteins in sarcomas and to determine their potential relationship; (2) use a tissue microarray to compare the immunohistochemical staining results on both the tissue microarrays and the corresponding whole tissue sections. METHODS Whole sections from 85 sarcomas were studied for the immunohistochemical expression of p53, c-kit and CD34.
Tissue microarrays consisting of triplicate 2 mm cores from the corresponding blocks were constructed and stained according to the same protocols as those used for the whole sections. RESULTS On whole section analysis, p53 protein was expressed in 25 cases (29.4%). Expression of c-kit was observed in 31 specimens (36.5%), whereas CD34 expression was noted in 11 tumors (12.9%). The overall concordance between triplicates was 96% (217/226). The consensus score from the combined triplicates agreed with the results on the whole sections at 91.4% (233/255). The correlations between p53 and CD34, and between c-kit and CD34, were statistically significant (p=.028 and p=.010 respectively). CONCLUSIONS p53 and c-kit express relatively frequently in sarcomas. Tissue microarrays are an effective alternative to whole sections; however, the presence of triplicate punches seems to improve the yield but not the concordance of data.
BACKGROUND Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract. The aim of this study is to investigate the correlation among the clinicopathologic features, presence of c-kit mutation, and immunohistochemical expression of c-kit in 61 cases of GISTs. METHODS We divided the GISTs into three groups as benign, boderline and malignant, according to histologic grade. Exon 11 of the c-kit was amplified by PCR and sequenced. We performed immunohistochemical study for CD117, CD34, vimentin, SMA, desmin, and S-100 protein. RESULTS Twenty-one cases were diagnosed as benign GISTs, 14 cases as borderline GISTs, and 26 cases as malignant GISTs.
The shape, atypia, cellularity, and necrosis showed good correlations with the histologic grades of the GISTs.Mutations of exon 11 of the c-kit were detected in 3 benign GISTs, 4 borderline GISTs, and 13(%) malignant GISTs.
Sequence analysis confirmed the deletion mutation (n=16) and the singlebase pair mutation (n=4). The immunohistochemical stainings showed myogenic differentiation(n=20), neurogenic differentiation (n=15), and neither myogenic or neurogenic differentiation(n=34). CONCLUSIONS The GIST is the primitive mesenchymal tumor capable of divergent differentiation, and the mutation of the c-kit is a good parameter for the malignant GIST.