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)

We report 28 testicular seminomas with cystic spaces of variable nature, sometimes accompanied by solid and hollow tubular patterns (12 cases). The spaces often suggested reticular or microcystic patterns of yolk sac tumor, and the solid and hollow tubular patterns often added to the diagnostic confusion. The tumors occurred in men 21 to 55 years old and on gross examination had the typical appearance of seminoma. On microscopic examination, the spaces ranged from small, closely packed and relatively regular to dilated, more dispersed and somewhat irregular. The hollow tubules appeared to result from central discohesion within nests of tumor. The spaces, particularly when large, often contained occasional tumor cells or inflammatory cells within pale edema fluid. The cytologic appearance of the cells lining the spaces, and in the surrounding tumor, retained the typical features of seminoma cells. Thirteen tumors (46%) either lacked (8 cases) or had very scant (5 cases) lymphocytes in the cystic and tubular areas, and hyaline globules were absent. Thirteen of 13 tumors were immunopositive for OCT-3/4 in the nontypical and typical areas; 9 of 10 were placental alkaline phosphatase positive, and 7 of 10 were c-Kit (CD117) positive. The same 13 cases were negative with cytokeratin (AE1/AE3) and alpha-fetoprotein stains. Distinction from yolk sac tumor is aided by the observation that the spaces of yolk sac tumor are often more irregular in their individual shapes and frequently form anastomosing channels. Additionally, the spaces of yolk sac tumor randomly merge with various other yolk sac tumor patterns. The cells lining spaces in yolk sac tumor are often flattened with compressed nuclei and lack the typical prominent nucleoli of seminoma cells. Paucity of lymphocytes and intracystic edema, however, are not differentially helpful, although basophilic fluid favors yolk sac tumor. A panel of immunostains (AE1/AE3, OCT-3/4, and alpha-fetoprotein) is helpful in the differential with yolk sac tumor in especially problematic cases. The edema and paucity of lymphocytes may suggest spermatocytic seminoma, but the varied cell types of that neoplasm are absent.
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PMID:Seminoma with tubular, microcystic, and related patterns: a study of 28 cases of unusual morphologic variants that often cause confusion with yolk sac tumor. 1576 5

We investigated the mechanism of phenotypic plasticity of hepatocytes in a three-dimensional organoid culture system, in which hepatocytic spheroids were embedded within a collagen gel matrix. Hepatocytes expressed several bile duct markers including cytokeratin (CK) 19 soon after culture and underwent branching morphogenesis within the matrix in the presence of insulin and epidermal growth factor. Cultured hepatocytes did not express Delta-like, a specific marker for oval cells and hepatoblasts. Furthermore, hepatocytes isolated from c-kit mutant rats (Ws/Ws), which are defective in proliferation of oval cells, showed essentially the same phenotypic changes as those isolated from control rats. The bile duct-like differentiation of hepatocytes was associated with increased expression of Jagged1, Jagged2, Notch1, and several Notch target genes. CK19 expression and branching morphogenesis were inhibited by dexamethasone, a mitogen-activated protein kinase kinase 1 (MEK1) inhibitor (PD98059), and a phosphatidyl inositol 3-kinase inhibitor (LY294002). After being cultured for more than 3 weeks within the gels, hepatocytes transformed into ductular structures surrounded by basement membranes. Our results suggest that hepatocytes might have the potential to transdifferentiate into bile duct-like cells without acquiring a stem-like phenotype and that this is mediated through specific protein tyrosine phosphorylation pathways.
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PMID:Transdifferentiation of mature rat hepatocytes into bile duct-like cells in vitro. 1579 88

Bioreactors containing porcine or adult human hepatocytes have been used to sustain acute liver failure patients until liver transplantation. However, prolonged function of adult hepatocytes has not been achieved due to compromised proliferation and viability of adult cells in vitro. We investigated the use of fetal hepatocytes as an alternative cell source in bioreactors. Mouse fetal liver cells from gestational day 17 possessed intermediate differentiation and function based on their molecular profile. When cultured in a three-dimensional four-compartment hollow fiber-based bioreactor for 3 to 5 weeks these cells formed neo-tissues that were characterized comprehensively. Albumin liberation, testosterone metabolism, and P450 induction were demonstrated. Histology showed predominant ribbon-like three-dimensional structures composed of hepatocytes between hollow fibers. High positivity for proliferating cell nuclear antigen and Ki-67 and low positivity for terminal dUTP nick-end labeling indicated robust cell proliferation and survival. Most cells within these ribbon arrangements were albumin-positive. In addition, cells in peripheral zones were simultaneously positive for alpha-fetoprotein, cytokeratin-19, and c-kit, indicating their progenitor phenotype. Mesenchymal components including endothelial, stellate, and smooth muscle cells were also observed. Thus, fetal liver cells can survive, proliferate, differentiate, and function in a three-dimensional perfusion culture system while maintaining a progenitor pool, reflecting an important advance in hepatic tissue engineering.
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PMID:Mouse fetal liver cells in artificial capillary beds in three-dimensional four-compartment bioreactors. 1625 12

PEComas, occasionally associated with the tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations. Because non-AML/non-LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26 PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior. All PEComas exclusive of AML and LAM were retrieved from our consultation files. Immunohistochemistry for pan-cytokeratin (CK), S-100 protein, smooth muscle actins (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed. The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm). Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10). Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases, necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25), desmin (8/22), HMB45 (22/24), Melan-A (13/18), MITF (9/18), S-100 protein (8/24), CK (3/23), vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7). Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of tuberous sclerosis complex. Recurrence and/or metastasis was strongly associated tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and necrosis. We conclude that PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small PEComas without any worrisome histologic features are most likely benign. PEComas with nuclear pleomorphism alone ("symplastic") and large PEComas without other worrisome features have uncertain malignant potential. PEComas with two or more worrisome histologic features should be considered malignant. Occasional PEComas express unusual markers, such as S-100 protein, desmin, and rarely CK. The role of TFE3 in PEComas should be further studied.
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PMID:Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. 1632 28

Mucinous tubular and spindle cell carcinoma, a rare, recently described distinctive subtype of renal cell carcinoma, may have some morphologic similarities to the more common papillary renal cell carcinoma, particularly the basophilic (type 1) tumors with prominent solid growth pattern. Tumor circumscription, compact tubular architecture, focal papillations, mucin production and foam cells (features seen in both papillary renal cell carcinoma and mucinous tubular and spindle cell carcinoma), as well as spindle cell morphology, have resulted in some cases sent to us in consultation with a question of possible sarcomatoid papillary renal cell carcinoma. In this study, tissue microarrays with triplicate samples each from 27 mucinous tubular and spindle cell carcinomas and 20 papillary renal cell carcinomas were created to simulate experience in renal biopsy specimens. From immunohistochemistry (IHC) data, published in the contemporary literature, a panel consisting of alpha-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), epithelial membrane antigen (EMA), renal cell carcinoma marker (RCC Ma), CD10, high molecular weight cytokeratin (HMWK), and c-kit was designed to test its utility in differential diagnosis. The immunoreactivity in mucinous tubular and spindle cell carcinoma was AMACR 93%, CK7 81%, EMA 95%, RCC Ma 7%, CD10 15%, HMWK 15%, and c-kit 5% and in papillary renal cell carcinoma was AMACR 95%, CK7 65%, EMA 88%, RCC Ma 25%, CD10 80%, HWMK 15%, and c-kit 18%. This largest study to date on IHC of mucinous tubular and spindle cell carcinoma dispels the specificity of AMACR for papillary renal cell carcinoma among the RCC subtypes. The histogenesis of mucinous tubular and spindle cell carcinoma from the distal nephron continues to be debatable, as our study showed the expression of the proximal convoluted tubule-related marker AMACR among these tumors. Thus, in tumors with predominant compact tubular growth and focal papillary architectures, careful attention to the presence of a low-grade spindle cell population may be helpful in the distinction of mucinous tubular and spindle cell carcinoma, as the key immunohistochemical stains for papillary renal cell carcinoma are also expressed in this subtype of renal cell carcinoma.
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PMID:Immunohistochemical analysis of mucinous tubular and spindle cell carcinoma and papillary renal cell carcinoma of the kidney: significant immunophenotypic overlap warrants diagnostic caution. 1633 Sep 37

In general, intrahepatic cholangiocarcinoma (ICC) is not related to liver cirrhosis. However, a few cases have been reported in which ICC was accompanied by severe liver fibrosis. Some researchers have proposed that hepatocellular and cholangiocellular (HC-CC) carcinoma, an intermediate mixed phenotype possibly arising in cirrhotic liver, might originate from hepatic precursor cells. In the liver, hepatocytes and cholangiocytes form the epithelial element, but stromal and mesenchymal elements may be produced by hepatic stem cells. Based on these aspects, not only HC-CC, but also other combinations of cellular phenotypes, would cover all the cancers with stem cell features. In this study, which aimed at determining the characteristics of the ICC phenotype, we used immunohistochemistry to examine the expression of basal/stem-cell markers, i.e., p63 in ICC with and without liver cirrhosis, as well as the expressions of cytokeratin (CK) 34 beta E12, specific for the basal-cell marker, and c-kit, specific for the stem-cell marker. Aberrant p63 was frequently expressed in ICC arising in cirrhotic liver. This result suggests that ICC cancer cells originate from hepatic precursor cells with a hidden multi-differentiation potential.
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PMID:Intrahepatic cholangiocarcinoma arising in cirrhotic liver frequently expressed p63-positive basal/stem-cell phenotype. 1637 99

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

Basal-like carcinomas have recently been identified in gene expression profiling studies as a subtype of invasive breast cancer. These lesions are estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative (triple negative), and typically express basal cytokeratins, epidermal growth factor receptor (EGFR), and/or c-kit. As poorly differentiated invasive ductal carcinomas, they presumably have a ductal carcinoma in situ (DCIS) precursor with similar cytologic and immunophenotypic features. However, the frequency and even the existence of a DCIS lesion with an immunophenotype analogous to that of invasive basal-like carcinomas have not been previously evaluated. We studied 66 cases of high nuclear grade DCIS using antibodies to ER, PR, HER2, three basal cytokeratins, EGFR, and c-kit to determine the frequency of the triple negative phenotype, and to determine the relationship between the triple negative phenotype and expression of basal cytokeratins and other biomarkers characteristically expressed by invasive basal-like carcinomas. Four cases (6%) exhibited the triple negative phenotype; the remaining cases showed other combinations of ER, PR, and HER2 expression (nontriple negative). Basal cytokeratins, EGFR, or both were expressed by all four triple negative lesions, but by only 21 of 51 (42%) nontriple negative cases (P = 0.04). We conclude that a small proportion of high-grade ductal carcinomas in situ exhibit an ER-negative/PR-negative/HER2-negative (triple negative) phenotype, and these lesions more commonly show expression of basal cytokeratins and/or EGFR than nontriple negative high-grade DCIS. Given that invasive breast cancers typically share immunophenotypic features with the ductal carcinoma in situ from which they arise, our findings raise the possibility that the triple-negative, basal cytokeratin and/or EGFR-positive DCIS lesions we identified represent a precursor lesion to invasive basal-like carcinomas.
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PMID:Ductal carcinoma in situ with basal-like phenotype: a possible precursor to invasive basal-like breast cancer. 1652 77

The incidence of retroperitoneal seminoma is much less than that of its gonadal counterpart. Accurate diagnosis of retroperitoneal seminoma is critical, because it carries an excellent prognosis due to its favorable response to radiation therapy and/or cisplatin-based chemotherapy. However, correctly diagnosing a retroperitoneal seminoma may be challenging, especially when the biopsy material is limited. The present study was conducted to evaluate histologic findings and immunohistochemical staining patterns in biopsy specimens of retroperitoneal seminoma and to compare their utility as diagnostic tools. Thirty biopsy specimens of retroperitoneal seminoma were assessed for histologic characteristics and immunohistochemical expression of OCT4, c-kit, placental-like alkaline phosphatase, and cytokeratin AE1/AE3. The clinical information, morphologic features, and staining intensities and the percentages of positively staining tumor cells were analyzed. The mean age of patients was 38 years. Lymphocytic infiltration and nucleolar prominence in tumor cells were found in all 30 cases (100%). The incidence of other histologic characteristics were as follows: fibrous septa/stroma in 80% (24 cases), clear tumor cell cytoplasm in 70% (21 cases), tumor necrosis in 60% (18 cases), cellular pleomorphism in 53% (16 cases), granulomatous inflammation in 50% (15 cases), distinct cell borders in 46% (14 cases), intercellular edema in 23% (7 cases), and syncytiotrophoblasts in 3% (1 case). The mean mitotic count was 3 (range 0 to 15) per 10 high-power fields. All 30 cases (100%) of retroperitoneal seminoma revealed moderate to strong nuclear OCT4 staining in more than 50% of tumor cells. Twenty-one cases (70%) showed membranous expression of c-kit by tumor cells, with moderate to strong staining intensity in most cases. Variable degrees of staining for placental-like alkaline phosphatase were identified in 23 cases (77%) with occasional background staining artifact. Six cases (20%) displayed a positive cytokeratin AE1/AE3 staining pattern with weak to moderate intensity. In conclusion, the most common histologic findings in limited biopsy specimens of retroperitoneal seminoma were lymphocytic infiltration and nucleolar prominence in tumor cell nuclei. OCT4 immunostaining, with its superior sensitivity and easy interpretation compared with other markers, is a powerful tool for confirming the diagnosis of retroperitoneal seminoma.
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PMID:Retroperitoneal seminoma in limited biopsies: morphologic criteria and immunohistochemical findings in 30 cases. 1672 57

Primary primitive neuroectodermal tumours (PNETs) of the bladder are extremely rare and aggressive neoplasms, and only six examples have been reported in the literature. The case of a 21-year-old woman, who remains disease free 3 years after tumour resection, is reported here. Morphological features were found to correspond to a small round blue cell tumour without rosette formation and with extensive areas of necrosis. Strong expression of CD99, vimentin and CD117 (c-kit), and focal reactivity to cytokeratin and S-100 protein was observed in tumour cells. Ultrastructurally, sparse neurosecretory granules were observed. Diagnosis of PNET was supported by molecular genetic analysis, showing the EWS-FLI-1 fusion transcript type 2 by RT-PCR and EWS gene rearrangement by fluorescence in situ hybridisation. A normal genetically balanced genotype was shown by comparative genomic hybridisation, which, together with the expression of c-kit, a known therapeutic target for imatinib, may have prognostic and therapeutic implications.
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PMID:Primary primitive neuroectodermal tumour of the urinary bladder: a clinico-pathological study emphasising immunohistochemical, ultrastructural and molecular analyses. 1680 53


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