Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soft tissue sarcomas in the first year of life are rare, and the most common sarcomas in infancy are embryonal rhabdomyosarcoma, Ewing sarcoma/primitive neuroectodermal tumor, congenital infantile fibrosarcoma, and primitive sarcomas such as undifferentiated sarcoma. In this study, we report 6 cases of a primitive myxoid mesenchymal tumor of infancy (PMMTI), which previously may have been included under the diagnostic categories of congenital-infantile fibrosarcoma or infantile fibromatosis. PMMTI occurred in 6 infants, 3 of whom had a congenital presentation of a soft tissue mass. All patients were otherwise healthy. The tumors occurred on the trunk, extremities, and head and neck. Grossly, the tumors were nonencapsulated and had a multinodular appearance with focal infiltrative growth, a white fleshy cut surface, and a tumor diameter ranging from 2 to 15 cm. Histologically, a diffuse growth of primitive spindle, polygonal, and round cells occurred in a myxoid background. The tumor cells were arranged in a vaguely nodular pattern with peripheral collagenized stroma, higher cellularity at the periphery, and a delicate vascular network in the background. Immunohistochemically, the tumors displayed diffuse reactivity for vimentin and no reactivity for smooth muscle actin, muscle specific actin, desmin, S-100 protein, or myogenin. Electron microscopy documented a poorly differentiated fibroblastic proliferation. Four cases tested negative for the ETV6-NTRK3 gene fusion by RT-PCR. One tumor had a complex karyotypic abnormality with rearrangements involving chromosomes Y, 9, and 3. Three patients had recurrences or metastasis treated with a combination of surgery and chemotherapy. One patient is alive with persistent locally aggressive disease, 2 are alive with no evidence of recurrence, 1 had a recurrence treated surgically without further follow-up information, 1 patient died with persistent tumor and sepsis 6 weeks after diagnosis, and 1 patient was lost to follow-up. The morphologic appearance combined with the ultrastructural features and absence of the typical gene rearrangement of congenital-infantile fibrosarcoma are unique, and we propose that PMMTI represents a new category of pediatric fibroblastic-myofibroblastic tumor.
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PMID:Primitive myxoid mesenchymal tumor of infancy: a clinicopathologic report of 6 cases. 1653 60

The authors studied the concordance among seven pathologists for the histologic diagnosis, interpretation of KIT immunostaining, and determining MIB-1 labeling indices (LI) in 80 adult patients with primary spindle cell tumors, mainly of the gastrointestinal tract, mesentery, retroperitoneum, and pelvis, based on the review of tissue sections using an immunohistochemical panel of antibodies for KIT/CD117, CD34, desmin, smooth muscle actin (SMA), and S-100 protein. Tumors included 30 gastrointestinal stromal tumors (GISTs), 10 leiomyomas, 10 leiomyosarcomas, 10 schwannomas, 10 solitary fibrous tumors, and 10 desmoid-type fibromatoses. The overall concordance with the original diagnosis of each histologic type was 97.9%, the kappa value ranging from 0.95 to 1.00 (mean 0.97), indicating a perfect agreement. The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.3%, the kappa value ranging from 0.77 to 0.90 (mean 0.86). The overall interlaboratory concordance with the original interpretation of KIT immunostaining was 91.9%, the kappa value ranging from 0.72 to 0.93 (mean 0.85). The overall concordance for determining MIB-1 LI was 90% with the original evaluation, and the overall kappa value ranged from 0.62 to 0.86 (mean 0.77). These results indicate that it is possible to reliably diagnose GIST and other spindle cell tumors of the gastrointestinal tract with the use of an immunohistochemical panel of antibodies for KIT, CD34, desmin, SMA, and S-100 protein. Although there is clearly unavoidable inter-observer and interlaboratory variability in the interpretation of KIT immunostained sections and interobserver variability in the determination of MIB-1 LI, the concordance between observes is very acceptable, and in most instances such variability can be eliminated by careful reviewing of the hematoxylin and eosin and immunostained sections.
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PMID:Interobserver variability in histologic recognition, interpretation of KIT immunostaining, and determining MIB-1 labeling indices in gastrointestinal stromal tumors and other spindle cell tumors of the gastrointestinal tract. 1654 Jul 30

We present an extensive immunohistochemical analysis of 7 mammary sarcomas that did not fit into any specific soft tissue sarcoma category. Histologically, they were composed of spindle cells with highly pleomorphic nuclei and abundant mitoses. Our immunohistochemical antibody panel included pan-cytokeratin (CK), basal cell type CKs (34betaE12, CK5/6, CK14, CK17) and vimentin antibodies, antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers, as well as antibodies to CD34, desmin, h-caldesmon, steroid receptors (estrogen, progesterone, androgen), and EGFR (Her-1). Whereas CKs, CD34, desmin, and h-caldesmon were not expressed, all tumors were positive for CD10 and vimentin. CD29 and SMA were observed in 3 cases each (43%), and p63 and calponin in 2 cases each (29%). Other myoepithelial markers and steroid receptors were absent, except androgen receptors, which were expressed in one sarcoma. Five sarcomas showed positivity for EGFR. The distinction of specific, histogenetically defined sarcoma entities (such as leiomyosarcoma, angiosarcoma, liposarcoma) from NOS-type sarcoma with CD10 expression is usually clear-cut because the former exhibit a characteristic histomorphology and immunoprofile. Phyllodes tumors with stromal overgrowth or recurrent phyllodes tumors lacking epithelial structures as well as periductal stromal sarcomas can be ruled out by their frequent expression of CD34 and negativity for myoepithelial markers. The most important differential diagnosis is sarcomatoid metaplastic carcinoma because its treatment includes axillary lymphadenectomy. Since some NOS-type sarcomas with CD10 expression and most metaplastic carcinomas show positivity for CD29, SMA, and p63, differential diagnosis can be extremely difficult and requires extensive immunohistochemical evaluation for CKs and additional myoepithelial markers such as S-100, 14-3-3sigma, and maspin. The immunophenotype of NOS-type sarcomas with CD10 expression suggests that these neoplasms represent a mammary sarcoma variant with myoepithelial features.
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PMID:Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of myoepithelial differentiation. 1662 90

Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. This study analyzed 1091 tumors originally classified as smooth muscle tumors of the small intestine (including jejunum or ileum and excluding duodenum), and found that 906 (83%) of these were GISTs. The GIST patients had 55:45 male-to-female ratio with a median age of 59 years (range, 13-94 years). Only 0.6% of tumors occurred before the age of 21 years and 13.6% before the age of 40 years. The tumors varied from 0.3 to 40 cm (median, 7.0 cm) and most commonly presented with GI bleeding or acute abdomen; 18% were incidentally detected. Histologically, the tumors were relatively monotypic with spindle cell (86%), epithelioid (5%), or mixed patterns (9%). Skeinoid fibers were present in 44% of cases, and their presence was associated with a favorable course. Most epithelioid tumors were malignant, and this morphology sometimes emerged from less cellular and less mitotically active spindle cell tumors, suggesting that it represented a transformation. KIT was immunohistochemically detected in 98%, CD34 in 40%, smooth muscle actin in 34%, desmin in 0.2%, and S-100 protein in 14% of the tumors tested. Outcome was strongly dependent on tumor size and mitotic activity, with an overall 39% tumor-related mortality, twice that for gastric GISTs. Only <3% of tumors <5 cm and < or = 5 mitoses/50 HPF metastasized, whereas 86% of tumors >10 cm and >5 mitoses/50 HPF metastasized. In stark contrast to corresponding gastric tumors, tumors >10 cm with mitotic activity < or = 5/50 HPF and those < or = 5 cm with mitoses >5/50 HPF had a high metastatic rate (>50%); tumors >5 cm < or = 10 cm with low mitotic rate had a 24% metastatic rate. The median survival times of patients with low mitotic rate tumors who died of disease decreased by increasing tumor size. KIT exon 11 mutations were detected in 90 cases, exon 9 mutation in 17 cases, and exon 17 mutation in 1 case; the presence of mutation or mutation type was not prognostically significant. There were no PDGFRA exon 12 or 8 mutations. Systematic data on prognosis of small intestinal GISTs of various size and mitotic activity categories can be helpful in management and surveillance of patients with these tumors.
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PMID:Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. 1700 Nov 71

We have previously described interstitial Cajal-like cells (ICLC) in human atrial myocardium. Several complementary approaches were used to verify the existence of ICLC in the interstitium of rat or human ventricular myocardium: primary cell cultures, vital stainings (e.g.: methylene blue), traditional stainings (including silver impregnation), phase contrast and non-conventional light microscopy (Epon-embedded semithin sections), transmission electron microscopy (TEM) (serial ultrathin sections), stereology, immunohistochemistry (IHC) and immunofluorescence (IF) with molecular probes. Cardiomyocytes occupy about 75% of rat ventricular myocardium volume. ICLC represent approximately 32% of the number of interstitial cells and the ratio cardiomyocytes/ICLC is about 70/1. In the interstitium, ICLC establish close contacts with nerve fibers, myocytes, blood capillaries and with immunoreactive cells (stromal synapses). ICLC show characteristic cytoplasmic processes, frequently two or three, which are very long (tens up to hundreds of microm), very thin (0.1-0.5 microm thick), with uneven caliber, having dilations, resulting in a moniliform aspect. Gap junctions between such processes can be found. Usually, the dilations are occupied by mitochondria (as revealed by Janus green B and MitoTracker Green FM) and elements of endoplasmic reticulum. Characteristically, some prolongations are flat, with a veil-like appearance, forming a labyrinthic system. ICLC display caveolae (about 1 caveola/ 1 microm cell membrane length, or 2-4% of the relative cytoplasmic volume). Mitochondria and endoplasmic reticulum (rough and smooth) occupy 5-10% and 1-2% of cytoplasmic volume, respectively. IHC revealed positive staining for CD34, EGFR and vimentin and, only in a few cases for CD117. IHC was negative for: desmin, CD57, tau, chymase, tryptase and CD13. IF showed that ventricular ICLC expressed connexin 43. We may speculate that possible ICLC roles might be: intercellular signaling (neurons, myocytes, capillaries etc.) and/or chemomechanical sensors. For pathology, it seems attractive to think that ICLC might participate in the process of cardiac repair/remodeling, arrhythmogenesis and, eventually, sudden death.
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PMID:Insights into the interstitium of ventricular myocardium: interstitial Cajal-like cells (ICLC). 1679 10

Gastrointestinal stromal tumor (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Most GISTs arise in the stomach and small bowel, whereas a small number occur elsewhere in the GI tract. Rare cases are identified outside the GI tract and are collectively known as extragastrointestinal stromal tumors (EGISTs). Because of their malignant potential and recent advances in the management of GISTs with imatinib mesylate (Gleevec, Glivec), it is imperative that these tumors are correctly diagnosed. In this study, we reviewed the clinical and pathologic characteristics of 3 cases of EGIST presenting as vulvovaginal/rectovaginal septal masses that were originally misdiagnosed, presumably due to their unusual anatomic locations. The original diagnoses were leiomyoma in one case and leiomyosarcoma in 2 cases. The lesions were localized to the rectovaginal septum () or vagina () and ranged from 4 to 8 cm in diameter. All 3 lesions had a spindle cell morphology that mimicked a smooth muscle tumor. Mitotic figures numbered from 12/50 to 16/50 high power fields (HPFs; median 15). Immunohistochemistry revealed that all 3 cases were strongly positive for KIT (CD117) and CD34 and negative for smooth muscle actin, desmin, pan-cytokeratin, and estrogen receptor. KIT sequence analysis revealed oncogenic mutations in all 3 cases. The first tumor recurred at 2 years and the second tumor recurred at 10 years; the third case is too recent for meaningful follow-up. EGISTs that present as gynecologic masses are rare but may be more common than is currently recognized. Misdiagnosis may lead to inappropriate therapy because conventional chemotherapy and radiotherapy are not effective in the treatment of GISTs, whereas imatinib mesylate (Gleevec, Glivec) has a proven role in managing these tumors. Thus, it is imperative to consider EGISTs in the differential diagnosis of mesenchymal neoplasms in the vulvovaginal/rectovaginal septum.
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PMID:Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: a diagnostic pitfall. 1681 68

Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.
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PMID:[Clinical guidelines for the management of gastrointestinal stromal tumors]. 1690 Aug 56

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms with an annual incidence of approximately 10 to 20 per 1 million cases. Although pathologists have often observed incidental small GISTs in the stomach resected from patients with gastric cancer, no report on the real incidence of gastric GISTs is available. In this study, 100 whole stomachs resected from patients with gastric cancer were sectioned at 5-mm intervals and hematoxylin and eosin-stained slides (a mean of 130 slides for each case) were examined for microscopic GISTs. KIT (CD117), CD34, and desmin expression of the incidental tumors was evaluated by immunohistochemistry, and genomic DNA extracted from formalin-fixed and paraffin-embedded tumor tissues was analyzed for c-kit gene mutations in exon 11. In 35 of the 100 whole stomachs, we found 50 microscopic GISTs, all of which were positive for KIT and/or CD34 and negative for desmin. Most microscopic GISTs (45/50, 90%) were located in the upper stomach. Two of the 25 (8%) microscopic GISTs had c-kit gene mutations. Fifty-one leiomyomas with positive expression for desmin were observed in 28 of the 100 stomachs. Both leiomyomas and GISTs were found in 12 stomachs. These results indicate that microscopic GISTs are common in the upper portion of the stomach. Considering the annual incidence of clinical GISTs, only few microscopic GISTs may grow into a clinical size with malignant potential. Further studies are required to clarify the genetic events responsible for the transformation of microscopic GISTs to clinical GISTs.
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PMID:High incidence of microscopic gastrointestinal stromal tumors in the stomach. 1699 66

The Carney triad is a rare syndrome of unknown aetiology, with synchronous or metachronous appearance of rare neoplasms: gastrointestinal stromal tumours (GISTs), pulmonary chondromas and extra-adrenal paragangliomas. In most cases, the Carney triad is incomplete. The combination encountered typically, GISTs and pulmonary chondromas, was also seen in our patient, a 22-year-old woman. She was diagnosed with the triad after Billroth II gastrectomy for histologically proved gastric GISTs. The diagnosis of pulmonary chondromas was confirmed by transthoracic, computed tomography-guided needle biopsy. An oesophageal leiomyoma was resected 2 years after the initial diagnosis, on suspicion of paraganglioma. The clinical course of the patient has been uneventful since. The last follow-up was carried out 6 years after the initial diagnosis. On histological examination, the cells of gastric GIST were partly positive for CD34, whereas CD117 was expressed in all areas in variable intensity and S-100 protein was negative. The oesophageal tumour was classified as leiomyoma due to strong immunopositivity for smooth muscle actin and desmin, being negative for CD34 and CD117. Two different gastric GIST lesions as well as the oesophageal leiomyoma and normal tissue were analysed for activating mutations in common hot spots of KIT (exon 9 and 11) and platelet-derived growth factor receptor alpha (exon 18), but in all probes wild-type sequences were found. These results are in accordance with the first published analyses of GIST lesions from Carney patients.
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PMID:A new case of Carney triad: gastrointestinal stromal tumours and leiomyoma of the oesophagus do not show activating mutations of KIT and platelet-derived growth factor receptor alpha. 1702 Nov 35

Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities. We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC. Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences). Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months. In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but none of our typical cases metastasized, although they can rarely arise contemporaneously with sarcomatoid urothelial carcinomas. For these reasons, close follow-up is warranted.
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PMID:Inflammatory myofibroblastic tumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma. 1712 5


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