Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we showed that Epstein-Barr virus (EBV)-positive gastric carcinoma (GC) forms a distinct clinicopathologic entity with a better prognosis due to lower incidence of lymph node metastases (LN+). Here we investigated whether in EBV-positive GC more pronounced activation of cellular immune responses is associated with absence of (micro)metastases. Twenty EBV-positive primary tumors (PT) (9 LN+) were matched with 28 EBV-negative GC (11 LN+) for T- and N-stage, gender, and age. The PT (n = 28) and its LNs were analyzed by EBER RNA in situ hybridization and by immunohistochemistry for MHC class I and II expression, for CD3, CD8, CD4, CD20, CD56, CD83, and Granzyme B (GzB) expression. In LN metastases of EBV-positive GC, the EBV genome is maintained, excluding tumor escape by virus deletion. All GC express MHC class I independently of EBV status. In comparison with EBV-negative GC, EBV-positive GC have higher expression of MHC class II on the tumor cells (P = 0.029) and a more extensive infiltrate (P < 0.0001) of activated GzB+ CD8+ T cells (P = 0.028), which is most abundant in those EBV-positive tumors that do not metastasize (P < 0.0001). In addition, in EBV-positive GC without metastases, the infiltrate contains higher numbers of mature dendritic cells (DC) (P = 0.018). At present, the antigenic target has to be determined. These data support the notion that local triggering of cellular immune responses in EBV-positive GC prevents lymph node metastasis formation.
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PMID:Morphological evidence of an activated cytotoxic T-cell infiltrate in EBV-positive gastric carcinoma preventing lymph node metastases. 1633 Sep 43

A solid-pseudopapillary tumor is an uncommon and "enigmatic" pancreatic neoplasm, and the term encompasses the two most conspicuous histological features: solid and pseudopapillary areas. Grossly, it appears as a large solid, cystic or solid-cystic mass frequently having necrotic and hemorrhagic zones. Histologically, solid-pseudopapillary tumors are generally characterized by solid areas alternating with a pseudopapillary pattern, and cystic spaces which are the results of degenerative changes occurring in the solid neoplasm. Its immunohistochemical pattern is very distinctive and neoplastic cells are consistently vimentin-, CD10- and CD56-positive. Some cases express focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin, neuron-specific enolase and synaptophysin. Progesterone receptors are frequently present. Keratins are not expressed or are found only focally. Endocrine and pancreatic enzyme markers are absent; the origin of solid-pseudopapillary tumors has not yet been clarified. Many investigators favor the theory that solid-pseudopapillary tumors originate from multipotent primordial cells while others suggest an extra-pancreatic origin from genital ridge angle-related cells. Some controversy exists for both hypotheses. Solid-pseudopapillary tumors appear as a low malignancy tumor and only a small number of cases recur or develop metastases after resection. No pathological factors were found to correlate with the prognosis. Some histological features have recently been suggested to be associated with aggressive behavior.
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PMID:Solid-papillary tumors of the pancreas: histopathology. 1640 35

Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.
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PMID:Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. 1672 45

Primary large cell neuroendocrine carcinomas (LCNEC) of the urinary bladder are rare. Reported herein is a case of a primary, pure LCNEC occurring in a man. The patient was a 32-year-old man who presented with hematuria of 1 week's duration. On cystoscopic examination, a solitary mass measuring 3 cm in diameter was detected protruding from the anterosuperior wall of the urinary bladder. Two months after the primary transurethral resection, significant regrowth of the remnant mass was noted on CT, and the patient underwent a partial cystectomy. A diagnosis of LCNEC was made based upon histological and immunohistochemical findings. Tumor cells were positive for synaptophysin, chromogranin A, CD56, epithelial membrane antigen, and cytokeratin. Histologically, the tumor penetrated the deep muscle and perivesical fat. In spite of three cycles of chemotherapy, the patient developed multiple metastases in the lung and liver 10 months postoperatively. LCNEC of the urinary bladder are uncommon entities, which have a possible fatal outcome.
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PMID:Primary large cell neuroendocrine carcinoma of the urinary bladder. 1704 Feb 93

Medulloblastoma is a primitive neuroectodermal tumor arising in the posterior fossa usually in the first decade of life. Systemic metastases are infrequent at diagnosis and usually occur after surgical resection or shunt placement. We report a rare case of medulloblastoma in an 18-year-old woman who presented with headache, leukopenia, and anemia. Neurologic examination was normal. Bone marrow evaluation revealed primitive cells morphologically resembling blasts. By flow cytometry, these cells lacked CD45 and expressed CD13/33, CD15, CD34, HLA-DR, and strong CD56. The presence of myeloid antigens and CD34 suggested acute myeloid leukemia; however, the bone marrow core biopsy architecture and tumor cells in cerebrospinal fluid were more compatible with a nonhematopoietic tumor. Further workup revealed a cerebellar mass, and a diagnosis of desmoplastic medulloblastoma was made. To our knowledge, this is the first reported case of a nonhematopoietic small round blue-cell tumor expressing multiple myeloid antigens and CD34 by flow cytometry.
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PMID:Medulloblastoma simulating acute myeloid leukemia: case report with a review of "myeloid antigen" expression in nonhematopoietic tissues and tumors. 1748 18

The number and function of human natural killer (NK) cells are generally assessed to monitor the baseline of immune function, the effect of treatment, the progress of malignancy or metastases and diseases. NK cells recognise and kill target cells in the absence of prior sensitisation and are able to defend the host from infection or prevent the progression of a disease. Human NK cells express CD16 and CD56 which are (massively) being used as a major hallmark for the NK cell. The purpose of this study was to identify the unique subsets of peripheral blood mononuclear cells (PBMC) (%CD3-CD56+ cells) by flow cytometry and to determine whether there is any correlation with functionally mature progeny of (NKp) precursor after five days of culture. The correlation was analysed using samples obtained from 120 Caucasian patients. 20-30ml of whole blood was collected in sterile tube containing preservative free sodium heparin and a similar sample was obtained after five days. Maturation of NKp required the continuous presence of recombinant interleukin 2 (rIL-2), or interleukin 15 (rIL-15) and functional maturity of NK cells was determined by their ability to lyse target cells from the K562 cell line. The NK precursor frequency was measured by limiting dilution analysis (LDA), which The NKpf assay was set up with a range of cell dilutions from 40,000 to 625 per 100ml/well in 96 well culture plates. At the end of the culture period the K562 cell line labelled with Europium (Eu-K562) was added and Eu release measured in culture supernatants using time-resolved fluorometry. The PBMC were set up in parallel cultures under various conditions . On day five cells were collected from culture plates and adjusted to 1x10 cells/ml and then mixed. The mixture was incubated and anti CD3 and anti CD56 were added. NK cells were enumerated in 120 patients by double staining with a combination of anti-CD3- and anti-CD56+. The results of these Immunophenotyping studies by flow cytometry showed no correlation between the NKpf (natural killer precursor frequency) and the percent of CD3-CD56+ cells expressed after five days confirming that CD56 was inadequate as a unique marker for functional NK cells.
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PMID:The correlation between the percent of CD3- CD56+ cells and NK precursor function. 1723 69

Inflammatory myofibroblastic tumor (IMT) is a neoplasm of intermediate biologic potential. In this study, we report a subset of IMTs with histologic atypia and/or clinical aggressiveness that were analyzed for clinicopathologic features, outcome, and immunohistochemical expression of anaplastic lymphoma kinase (ALK) and other markers to identify potential pathologic prognostic features. Fifty-nine IMTs with classic morphology (5 cases), atypical histologic features (21 cases), local recurrence (27 cases), and/or metastasis (6 cases) were studied. Immunohistochemistry was performed for ALK1 and other markers (Mib-1, c-Myc, cyclin D1, caspase 3, Bcl-2, Mcl-1, survivin, p27, CD56, p53, MDM-2) using standard techniques. The 59 IMTs had an age at diagnosis ranging from 3 weeks to 74 years (mean 13.2 y, median 11 y, 44% in the first decade). The mean tumor size was 7.8 cm. Sites included the abdomen or pelvis in 64%, lung in 22%, head and neck in 8%, and extremities in 5%. The follow-up ranged from 3 months to 11 years, with a mean of 3.6 years and a median of 3 years. Thirty-three patients had local recurrences, including 13 with multiple local recurrences and 6 patients with both local recurrences and distant metastases. Six patients died of disease, 5 with local recurrences, and 1 with distant metastases. Histologic evolution to a more pleomorphic cellular, spindled, polygonal, or round cell morphologic pattern was observed in 7 cases. Abdominal and pelvic IMTs had a recurrence rate of 85%. Recurrent and metastatic IMTs were larger, with mean diameters of 8.7 and 11 cm, respectively. Cytoplasmic ALK reactivity was seen in 56%. ALK-negative IMTs occurred in older patients (mean age 20.1) years and had greater nuclear pleomorphism, atypia, and atypical mitoses. All 6 metastatic IMTs were ALK-negative. Nuclear expression of p53 was detected in 80% of IMTs overall, but in only 25% of the metastatic subset. There were no significant differences among the subgroups for c-Myc, cyclin D1, MDM-2, Mcl-1, Bcl-2, CD56, p27, caspase 3, or survivin expression. In conclusion, among these 59 IMTs, ALK reactivity was associated with local recurrence, but not distant metastasis, which was confined to ALK-negative lesions. Absent ALK expression was associated with a higher age overall, subtle histologic differences, and death from disease or distant metastases (in a younger subset). Other proliferative, apoptotic, and prognostic markers did not correlate well with morphology or outcome. Thus, ALK reactivity may be a favorable prognostic indicator in IMT and abdominopelvic IMTs recur more frequently.
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PMID:Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. 1741 97

The expression of NCAM was investigated in tissue sections of 61 cases of papillary carcinoma and in 14 lymph node metastases using immunohistochemistry. Tumour cells of 18 primary tumours were not stained, whereas in the remaining 43 cases, NCAM was expressed in less than 5% tumour cells. Similar results were obtained when NCAM expression was evaluated at the RNA level. Reduced expression of NCAM is an early event since 6/15 cases (40%) of micro-carcinoma were NCAM-negative. NCAM-positive tumour cells were more often located at the invasion front of the tumour. It has been reported that NCAM expression may affect lymphangiogenesis. In tissue sections immunostained for podoplanin, it was found that lymphatic vessels were extremely rare inside the body of the tumour, and were mostly associated with foci of chronic inflammation and/or of reparative fibrosis. Lymphangiogenesis is sustained by VEGF-C, VEGF-D, and FGF2. Analysis of micro-dissected samples of the tumour and of the paired normal thyroid tissue revealed that RNA transcripts for VEGF-D were significantly less numerous in the tumour tissue (p = 0.001). The potential role of NCAM in tumour cell biology was investigated by silencing the NCAM gene in the TPC1 thyroid papillary carcinoma cell line. It was found that NCAM down-regulation caused a significant reduction (p < 0.05) in the expression of both VEGF-C and VEGF-D mRNAs. In addition, NCAM-silenced TPC-1 cells were more adhesive to different extracellular matrix components, and were less efficient in cell migration (59% reduction; p < 0.05) and invasiveness (68% reduction). These latter results confirm that modifications of NCAM expression cause profound alterations in the adhesive and migratory properties of tumour cells, but are in apparent discrepancy with the observation that loss of NCAM is usually associated with increased tumour invasiveness in vivo.
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PMID:Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is associated with downregulation of VEGF-D production by tumour cells. 1757 72

A 69-year-old male with tinnitus, vertigo, and progressive hearing loss of left ear was admitted to our hospital. Head magnetic resonance imaging and computed tomography (CT) revealed swelling of multiple neck lymph nodes (LNs) invading the skull base, which involved left mastoid sinus/the eighth cranial nerve. Biopsy of the cervical LN demonstrated small-cell carcinoma (SCC). Whole body CT showed systemic lymphadenopathies (subclavian, para-aortic, and bilateral iliac LNs) and prostatic swelling with multiple pelvic masses. Needle biopsy of the prostate revealed SCC (Gleason score: 5+ 5). Immunohistochemically, neuron-specific enolase (NSE) and NCAM were detected in <10% and -100% of cancer cells, respectively. Despite SCC histology, prostate-specific antigen (PSA) and androgen receptor (AR) were also expressed in -20% and -70% of tumor cells, respectively. Serum PSA and NSE were 464 ng/ml and 12 ng/ml, respectively. After maximum androgen blockade (MAB) with leuprorelin/bicalutamide, the patient showed recovery of hearing loss, regression of cervical LNs (partial response), and decline of serum markers (PSA 7.38 ng/ml and NSE 3.7 ng/ml, respectively). As re-increase of PSA was observed after ten months, MAB menu was changed to leuprorelin/fultamide. Another four months later, the treatment was changed to docetaxel/ estramustine due to the appearance of systemic bone pain and recurrence of LN metastases. He is alive (39 months after diagnosis) with cancer. Widespread metastases at the time of diagnosis were compatible with SCC. However, this case was AR-positive and responded to androgen ablation, at least temporarily. Even though the initial symptoms are atypical for a prostatic carcinoma, SCC of prostate needs to be included as a rare differential diagnosis.
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PMID:[Prostatic carcinoma that arose with hearing loss: a case report]. 1762 42

We report 20 cases of a distinct, previously unrecognized renal neoplasm, anaplastic sarcoma of the kidney with polyphenotypic features. The tumors were identified by re-reviewing tumors with unusual anaplastic features from the National Wilms Tumor Study Pathology Center, the International Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group trials. Patients ranged in age from 10 months to 41 years (median age 5 y, mean age 12 y) and females predominated (1.5:1). Twelve tumors presented in the right kidney, and 5 in the left (laterality was unknown in 3 cases). The most common presentation was a renal mass. Grossly, most tumors were large, measured 4 to 21 cm (mean 12.7 cm) and weighed 115 to 1820 g (mean 835 g). Seven out of 12 tumors suitable for assessment had a distinct cystic component. The tumors involved the pelvi-calyceal system in 5 of the cases. Histologically, all tumors showed a spindle cell component which contained either multiple foci or diffuse, widespread anaplastic changes with bizarre pleomorphic cells and very atypical mitotic figures. Chondroid differentiation was seen in 16 cases, usually in the form of islands of hyaline cartilage (13 cases) or chondroid matrix (3 cases). The nodules of cartilage showed both benign and malignant features, often within the same tumor. In 2 cases small foci of osteoid were found whereas osteoclast-like giant cells were seen in 4 cases. Only 3 of the tumors exhibited a primitive blastema-like area. No neoplastic epithelial structures were identified. No nephrogenic rests were found. Limited immunohistochemical studies showed vimentin positivity in 5/5 cases, desmin was positive in 4/6 cases, MYF4 showed focal weak nuclear positivity in 1/4 cases, but MyoD1 was negative in all cases (0/5). PGP9.5 was focally, strongly positive in 4/5 cases and p53 was strongly positive in 3/6 cases. Cytokeratin, using the antibody CAM5.2, was uniformly negative within the tumor cells. Finally, CD56 was focally positive in 1/6 tumors, whereas all other markers were negative including NB84a (4/4), CD34 (5/6), CD99 (5/5), and WT1 (6/6 cases). In 4 tumors reverse transcriptase-polymerase chain reaction was performed to detect the SYT-SSX fusion transcript produced by the t(x;18), and the ETV6-NTRK3 fusion transcript using RNA extracted from archived paraffin blocks-results were negative in all 4 specimens. Tumor stage was known in 15 patients including 7 stage I, 4 stage II, 3 stage III, and 1 stage IV tumors. They were usually diagnosed as anaplastic Wilms tumors and treated accordingly. Of the 13 patients with a minimum of 2 years follow-up, 4 patients developed distant metastases and 1 had local recurrence including 1 patient with stage IV, 2 with stage III, and 2 with stage I at presentation. Three of them died and 2 were lost to follow-up. One patient with stage I tumor developed widespread metastases and died. Another stage I patient developed local recurrence after 3 months of diagnosis, but was lost to follow-up. Five stage I patients were alive and free of tumor at last follow-up. The most common sites of metastases were lung (3 cases), and liver and bones (2 cases each). These tumors showed pathologic features similar to the pleuropulmonary blastoma of childhood and undifferentiated (embryonal) sarcoma of the liver. In the differential diagnosis, anaplastic Wilms tumor, primary renal synovial sarcoma, malignant mesenchymoma, ectomesenchymoma, and mesenchymal chondrosarcomas have been considered but none of these tumors shared the same features as the 20 cases described here which represent a distinct clinicopathologic entity with morphologic features of a polyphenotypic anaplastic sarcoma of the kidney. Further molecular studies are needed to better understand its nature and more accurate classification.
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PMID:Anaplastic sarcoma of the kidney: a clinicopathologic study of 20 cases of a new entity with polyphenotypic features. 1789 46


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