Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nasal natural killer/T-cell lymphoma (N-NK/T-L) is prevalent in China. To further characterize this neoplasm, 36 cases of N-NK/T-L from 304 cases of malignant lymphomas in the north China area were investigated by histopathology, immunophenotyping, and genomic analysis of c-kit, in comparison with 11 cases of B-cell lymphoma (BCL) at the same region and 5 cases of nodal peripheral T-cell lymphoma (PTCL) (unspecified). Histopathologically, N-NK/T-L was characterized by coagulative necrosis, inflammatory background, and angiodestructive growth pattern. In 36 cases of N-NK/T-L, 27 cases (75.0%) were stained for CD45RO and 25 (72.2%) for CD3epsilon. Thirty cases (83.3%) were positive for T-cell intracellular antigen-1, 22 (61.1%) for granzyme B, 18 (50.0%) for CD56, and 11 (30.6%) for CD30, whereas none was positive for CD117. All 5 cases of PTCL displayed positive staining for CD45RO and T-cell intracellular antigen-1, 3 cases for CD3epsilon, but only 1 case for granzyme B. All 11 BCLs presented positive staining for CD20 and CD79a but negative for other antibodies. A significant relationship was observed between neoplastic cells pleomorphism and granzyme B expression (P < .05). Despite the fact that all cases were negative for CD117 staining, genomic sequences of c-kit 11 and exon 17 sequencing showed that 8 (26%) of 31 cases N-NK/T-L proved to contain genomic mutations, including 4 cases in exon 11 and 4 in exon 17. For the control group, only 1 (9%) of 11 BCLs and 1 (20%) of 5 cases of PTCL were detected to harbor mutations in exon 11. All mutations detected in 3 groups were missense by base substitution, and codes 571, 572, and 821 were hot spots. The results suggested that, in addition to histological features and routine immunophenotyping, granzyme B expression should be a more reliable marker in correct diagnosis of N-NK/T-L, and genetic analysis of c-kit mutation should be helpful in the diagnosis of this tumor.
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PMID:Immunohistochemical and genetic analysis of Chinese nasal natural killer/T-cell lymphomas. 1636 Apr 16

Natural killer cells are important innate immune effector cells with potentially broad applications in the treatment of human malignancy due to their ability to lyse neoplastic cells without the need for tumor-specific antigen recognition. Human NK cells can be divided into two functional subsets based on their surface expression of CD56; CD56(bright) immunoregulatory cells and CD56(dim) cytotoxic cells. In addition to functional differences, these NK cell subsets can be modulated differently by interleukin (IL)-2, which has permitted the development of lower dose, better tolerated IL-2 regimens for the in vivo expansion and activation of NK cells. The importance of early hematopoietic growth factors, such as c-kit ligand and flt-3 ligand, and their synergy with IL-15 in the development of human NK cells in the bone marrow has permitted the investigation of novel cytokine combinations for optimizing in vivo expansion of NK cell in the clinic. The importance of lymph nodes as a site for NK cell development has recently been elucidated. Furthermore, progress in the field of how NK cell recognize target cells via activating and inhibitory receptors, and how the balance of signals from these receptors can modulate NK cell activity has revolutionized our understanding of the selective killing of tumor cells by NK cells while sparing normal cells. In this review, we summarize current understanding of NK cell biology, and highlight how such knowledge may be translated to optimize the efficacy of using autologous or allogeneic NK cell for the immunotherapy of cancer.
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PMID:Human natural killer cell development and biology. 1636 19

We describe a hitherto undocumented variant of dimorphic pituitary neoplasm composed of an admixture of neurosecretory cells and profuse leiomyomatous stroma around intratumoral vessels. Radiologically perceived as a macroadenoma of 3.8 cm in diameter, this pituitary mass developed in an otherwise healthy 43-year-old female. At the term of a yearlong history of amenorrhea and progressive bitemporal visual loss, subtotal resection was performed via transsphenoidal microsurgery. Discounting mild hyperprolactinemia, there was no evidence of excess hormone production. Histologically, solid sheets, nests and cords of epithelial-looking, yet cytokeratin-negative cells were seen growing in a richly vascularized stroma of spindle cells. While strong immunoreactivity for NCAM, Synaptophysin and Chromogranin-A was detected in the former, the latter showed both morphological and immunophenotypic hallmarks of smooth muscle, being positive for vimentin, muscle actin and smooth muscle actin. Architectural patterns varied from monomorphous stroma-dominant zones through biphasic neuroendocrine-leiomyomatous areas, to pseudopapillary fronds along vascular cores. Only endothelia were labeled with CD34. Staining for S100 protein and GFAP, characteristics of sustentacular cells, as well as bcl-2 and c-kit was absent. Except for alpha-subunit, anterior pituitary hormones tested negative in tumor cells, as did a panel of peripheral endocrine markers, including serotonin, somatostatin, calcitonin, parathormone and vasoactive intestinal polypeptide. Mitotic activity was absent and the MIB-1 labeling index low (1-2%). While assignment of this lesion to any established neoplastic entity is not forthcoming, we propose it is being considered as a low-grade neuroendocrine tumor possibly related to null cell adenoma.
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PMID:Leiomyomatoid angiomatous neuroendocrine tumor (LANT) of the pituitary: a distinctive biphasic neoplasm with primitive secretory phenotype and smooth muscle-rich stroma. 1652 Sep 66

Hepatic stem cells can be identified by the expression of putative markers such as CD117 (c-kit), CD90 (Thy-1), CD34, and HLA-DR. We have identified populations expressing these markers in both fetal and tumoral human liver by flow cytometry, using monoclonal antibodies against CD90, CD117, CD34, and HLA-DR. In tumoral liver CD117+/CD90+ cells were found in decreasing number from the neoplastic (2.48 +/- 0.67) and peritumoral region (0.88 +/- 0.12) to the area of para-tumoral (normal) parenchyma (0.13 +/- 0.04). The CD117+/CD34+ cells showed the following distribution: 0.35 +/- 0.05% in the tumoral region, 1.01 +/- 0.23% in the peritumoral region and 0.35 +/- 0.01 in the para-tumoral region. Using the same markers on fetal liver cells we have also identified small populations of CD117+/CD90+ cells (0.28 +/- 0.07%) and CD117+/CD34+ cells (1.13 +/- 0.24%), presumably resident stem cells or hematopoietic stem cells. Immunomagnetic negative separation was then performed on fetal liver cells using monoclonal antibodies against specific markers of hematopoietic lineages such as CD3, 14, 16, 19, 22, and CD56 to eliminate this population. The remaining cells were then incubated with fluorescently labeled monoclonal antibodies against CD90 and CD117 and analyzed using fluorescence microscopy. As expected these markers were expressed on the majority of the selected cells (89.28 +/- 9.56%). Isolation using appropriate markers and initiation of primary cultures is a first step to the therapeutic use of fetal stem cells and for the study of adult liver stem cells involvement in carcinogenesis.
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PMID:[Expression of stem cell markers on fetal and tumoral human liver cells in primary culture]. 1660 35

The concept of lymphoid differentiation in the human gastrointestinal tract is controversial but is the focus of this study, which examined adult human small intestinal tissue for the presence of CD34(+)CD45(+) hemopoietic stem cells (HSCs) and lymphoid progenitors. Flow cytometry demonstrated that over 5% of leukocytes (CD45(+) cells) isolated from human gut were HSCs coexpressing CD34, a significantly higher incidence than in matched peripheral blood or control bone marrow. HSCs were detected in cell preparations from both the epithelium and lamina propria of all samples tested and localized to the intestinal villous and crypt regions using immunofluorescence. A high proportion of gut HSCs expressed the activation marker CD45RA, and few expressed c-kit, indicating ongoing differentiation. The vast majority of intestinal HSCs coexpressed the T cell Ag, CD7 (92% in the epithelium, 80% in the lamina propria) whereas <10% coexpressed the myeloid Ag CD33, suggesting that gut HSCs are a relatively mature population committed to the lymphoid lineage. Interestingly, almost 50% of epithelial layer HSCs coexpressed CD56, the NK cell Ag, compared with only 10% of the lamina propria HSC population, suggesting that the epithelium may be a preferential site of NKR(+) lymphoid differentiation. In contrast, bone marrow HSCs displayed low coexpression of CD56 and CD7 but high coexpression of CD33. The phenotype of intestinal HSCs, which differs significantly from circulating or bone marrow HSCs, is consistent with a role in local lymphoid development.
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PMID:Detection and characterization of hemopoietic stem cells in the adult human small intestine. 1662 84

Small cell carcinoma of the prostate (SCPC) is morphologically similar to small cell carcinoma of the lung (SCLC) and maybe misinterpreted as Gleason pattern 5b prostate adenocarcinoma (HGPC). Recognition of SCPC is important because of its different clinical behavior. This study aims to characterize the immunophenotype of histologically classic SCPC using a comprehensive panel of markers, to better understand its histogenesis, aid in its classification, and evaluate potential therapeutic targets. Using the World Health Organization morphologic criteria for SCLC, 18 SCPC cases were identified; and studied for the following tumor marker groups: prostate specific/related, neuroendocrine, sex steroid hormone receptors, and prognostic/treatment target-related. Ten cases of UPC were used as controls. PSA was positive in 17% of SCPC and neuroendocrine markers were expressed in HGPC. PSA, TTF-1 and CD56 were the most helpful markers in differentiating between SCPC and HGPC (P<0.01), whereas bombesin/GRP, c-kit, bcl-2, and EGFR expression was more frequent in SCPC. SCPC is best diagnosed by following the World Health Organization diagnostic criteria for SCLC. Immunohistochemical markers can help separate SCPC from HGPC and may be useful in histologically borderline cases. Potential therapeutic targets are identified immunohistochemically in SCPC (Bombesin/GRP, c-kit, bcl-2, and EGFR).
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PMID:Small cell carcinoma of the prostate: an immunohistochemical study. 1672 47

Small cell neuroendocrine carcinoma is a type of undifferentiated, malignant neuroendocrine tumor. Most of neuroendocrine tumors exhibit well-differentiated features and are classified as carcinoid tumors. However, carcinomas of the liver with anaplastic characters, which are classified as small-cell carcinomas are extremely rare and only few cases have been reported in the literature. We report an unusual case of primary small cell neuroendocrine carcinoma of the liver in a 67-year-old man. The patient was found to have a palpable mass on right upper quadrant of abdomen on physical examination. The diagnosis was made by immunohistochemical stains of biopsied specimen from the liver. Other possible primary site was excluded by radiologic and endoscopic evaluations. The tumor was composed of small monotonous and hyperchromatic poorly differentiated cells with higher nuclear to cytoplasmic ratio, and were positive for neuroendocrine tissue markers such as synaptophysin, c-kit, and CD56.
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PMID:[A case of primary small cell neuroendocrine carcinoma of the liver]. 1686 80

Nonsmall cell neuroendocrine carcinoma (NSCNEC) of the ovary is a rare and aggressive tumor commonly associated with other surface epithelial and germ cell neoplasms. In this study, we present the clinicopathologic and immunohistochemical features of 11 such cases seen at The University of Texas M.D. Anderson Cancer Center in a 16-year period (1990 to 2005). Patients ranged in age from 22 to 63 years (mean 46.7). The most common presentation was abdominal/pelvic pain (6 cases), followed by ascites (2 cases), pelvic mass, vaginal bleeding, and abdominal bloating (1 case each). Tumors were mostly unilateral, cystic, or solid/cystic and ranged in size from 5 to 26 cm (mean 16.2). In 8 cases, NSCNEC was associated with other epithelial neoplasms, including mucinous neoplasms of low malignant potential, mucinous carcinoma, endometrioid carcinoma, mixed endometrioid and mucinous carcinoma, and a high-grade carcinoma, not otherwise specified. In 2 cases, the tumor was associated with a mature cystic teratoma; one of them also containing an invasive moderately differentiated adenocarcinoma. A single case was associated with a benign ovarian cyst. The latter case had a dermoid cyst in the contralateral ovary. NSCNEC represented anywhere from 10% to 90% of the ovarian tumor. Microscopically, the neuroendocrine component was usually composed of large and/or intermediate oval to round cells. In 2 cases, the intermediate cells were intermixed with small cells. Three cases had also spindle cells. The neoplastic cells were mostly arranged in a solid pattern, nests, or trabeculae. All tumors had a brisk mitotic activity. Immunoperoxidase studies for keratin cocktail, cytokeratin (CK) 7, CK20, CAM 5.2, chromogranin A, synaptophysin, NSE, CD56, and c-kit were performed and the cases stained as follows: keratin cocktail 6/6, CK7 4/5, CK20 3/5, CAM 5.2 3/3, chromogranin A 8/11, synaptophysin 9/9, NSE 1/1, CD56 4/8, and c-kit 5/7. According to the International Federation of Gynecology and Obstetrics staging system, 4 cases were stage I tumors, 3 cases were stage III tumors, and 4 cases were stage IV tumors. Seven patients were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy. One patient had a bilateral salpingo-oophorectomy with omentectomy and appendectomy followed by chemotherapy; 1 patient had a total abdominal hysterectomy with right salpingo-oophorectomy followed by chemotherapy; one had a bilateral salpingo-oophorectomy followed by chemotherapy, and one had a right salpingo-oophorectomy with appendectomy followed by chemotherapy. Five patients died of disease at 2, 3, 9, 20, and 36 months. One patient is alive with disease at 8 months and 5 are alive without evidence of disease at 11, 28, 37, 66, and 68 months. Four of 5 patients who died of disease had either stage III or IV tumors and 3 of 5 patients who are alive without evidence of disease have stage I tumors. In summary, ovarian NSCNEC is an aggressive tumor with a tendency to present at advanced stage and cause death within a mean of 17 months after diagnosis; however, some patients, particularly those with stage I disease and/or those who have received platinum-based therapy, may have a more favorable prognosis.
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PMID:Ovarian nonsmall cell neuroendocrine carcinoma: a clinicopathologic and immunohistochemical study of 11 cases. 1746 Apr 63

Patients with primary small cell carcinoma of the liver have rarely been described in medical literature. Knowledge of clinical, pathological and immunohistochemical properties remains limited. We described an 82-year-old female patient with primary small cell carcinoma of the liver. Histologically, the tumor showed typical morphology of a pulmonary small cell carcinoma. Immunohistochemically, the tumor revealed neuroendocrine differentiation; positive reaction for chromogranin, synaptophysin, CD56, and neuron specific enolase. The tumor was also positive for TTF-1 and c-kit but completely negative for hepatocyte, carcinoembryonic antigen, cytokeratin 7; 19; and 20. Herein, we discussed the clinical, pathological and immunohistochemical findings of extrapulmonary small cell carcinoma of the liver and reviewed the relevant literature.
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PMID:Extrapulmonary small cell carcinoma of the liver: clinicopathological and immunohistochemical findings. 1815 5

Clear cell sarcoma (CCS) of soft tissue is a rare sarcoma with morphologic similarities to malignant melanoma but a distinct genetic background including a chromosomal translocation, t(12;22)(q13;q12), or a resultant EWSR1-ATF1 fusion gene. In addition, the tumors occurring in the gastrointestinal tract may have a variant fusion gene EWSR1-CREB1. This study analyzed the clinicopathologic and molecular genetic features of 33 CCSs of soft tissue. The patients' ages ranged from 13 to 73 years (median, 30 y), and there was a male predominance (20 males, 13 females). The tumors were located in the deep soft tissues of the extremities (N=25) or in the trunk or limb girdles (N=8). The median tumor size was 4 cm (range, 1 to 15 cm). The tumor cells were either spindle or epithelioid, and they were arranged predominantly in a short fascicular (N=19) or a solid sheetlike growth pattern (N=14). Minor histologic variations included the existence of rhabdoid cells (N=8), bizarre pleomorphic cells (N=6), alveolar structures due to loss of cellular cohesion (N=3), and a seminomalike pattern (N=2). Tumor necrosis was evident in 14 tumors, and the mitotic activity ranged from 0 to 43 mitotic figures (MF)/10 high-power fields (HPF) (mean: 4 MF/10 HPF). Immunohistochemically, the tumors were consistently positive for S-100 protein (33/33) and variably or focally for HMB45 (32/33), microphthalmia transcription factor (26/32), Melan A (23/32), CD57 (25/33), bcl-2 (30/32), synaptophysin (14/32), CD56 (7/32), epithelial membrane antigen (12/33), cytokeratin (AE1/AE3) (1/32), CD34 (3/32), c-erbB-2 (10/32), c-kit (5/32), and c-met (5/32). alpha-Smooth muscle actin, desmin, and cytokeratin (CAM5.2) were negative. Reverse transcription-polymerase chain reaction using RNA extracted from formalin-fixed, paraffin-embedded tissues demonstrated transcripts of the EWSR1-ATF1 (31/33) or EWSR1-CREB1 fusion gene (2/33). In 26 cases with available clinical information, local recurrences and metastases developed in 2 and 15 patients, respectively. Ten patients were dead of the disease, and the overall survival rate was 63% at 5 years. However, no clinicopathologic or molecular variables associated with the patients' prognosis were identified. This study confirms that CCS is an aggressive soft tissue tumor with a melanocytic phenotype and wider morphologic variations than had been generally considered. In cases with unusual histologic findings, molecular detection of the EWSR1-ATF1/CREB1 fusion genes provides critical information regarding the diagnosis of the tumor.
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PMID:Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. 1830 Aug 4


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