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

Hepatocellular carcinoma (HCC) is known for its histomorphologic heterogeneity. Immunohistochemistry (IHC) can help in the comparative morphologic evaluation of HCC, its variants and their mimics. Some of these diagnostic challenges can be attributed to (i) the variety of neoplasms that can arise from the hepatic stem cell lineage; (ii) the spectrum of well-differentiated hepatocellular nodular lesions; (iii) the liver being a target for metastases with some of these histologic entities mimicking variants of HCC or actually arising in the liver; and (iv) the limitations of serum alpha-fetoprotein (AFP). The role of IHC is in the distinction of benign hepatocellular nodules from reactive hepatocytes; WD-HCC from benign hepatocellular nodules; poorly differentiated HCC from cholangiocarcinoma and metastases; and determination of histogenesis of malignant tumor; and of primary site of origin of malignant tumor. A panel of antibodies has more discriminant value. AFP expression usually indicates malignancy in a hepatocellular nodule and hepatocytic histogenesis of a malignancy. Polyclonal carcinoembryonic antigen (pCEA) and CD10 stain bile canaliculi in better-differentiated HCC. HepPar1 is generally accepted as a hepatocytic marker. However, not all HCC stain uniformly and not all HepPar1-positive tumors are of hepatocytic origin or arise in the liver. Mature hepatocytes and hepatocellular nodules stain with CAM 5.2, CK 8, and 18 but not with CK 7, 19, 20, or AE1/AE3. Biliary epithelium expresses CK 7 and 19. CD 34 highlights sinusoidal capillarization. AFP, pCEA/CD10, and CD34 are useful for ascertainment of malignancy in hepatocellular nodules; HepPar1 and cytokeratins to be included if histogenesis is the issue. IHC results should be interpreted in the larger context of the case.
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PMID:Diagnostic utility of immunohistochemistry in hepatocellular carcinoma, its variants and their mimics. 1693 16

Pleomorphic tumors with giant cells have been described in a variety of primary sites. However, only a few cases have been described among prostatic carcinomas with only 1 on diagnostic biopsy material. Five cases were retrieved from the consultation files of one of the authors. One of the cases was retrieved from the surgical pathology files at our institute. Patient ranged in age from 59 to 76 years (mean=65.8 y). The diagnosis was made on needle biopsy (n=3), urethral biopsy (n=1), transurethral resection (n=1), or radical prostatectomy (n=1). In all cases, giant, bizarre, anaplastic cells were present. In 4 of the cases, marked pleomorphism occupied 5% of the specimen, with 20% and 70% bizarre giant cells in the other 2 cases. In one case, the bizarre cells had atypical mitotic figures, with other cases showing no mitoses in the markedly pleomorphic cells. In addition to the pleomorphic giant cell component, multiple coexistent histologic components were seen including Gleason score 9 conventional prostate cancer (n=6), small cell carcinoma (n=1), squamous carcinoma (n=1), and prominent ductal adenocarcinoma differentiation with intraductal spread (n=1). Immunohistochemically, 4 cases were for negative for prostate-specific antigen in the giant cells, 1 had 5% staining, and the other had 50% positivity in the giant cells. Staining for prostate-specific antigen in the conventional prostate carcinoma component was 1%, 5%, 20%, 50%, 100%, and 100%. The bizarre giant cells were strongly positive for cytokeratins AE1/AE3 and/or Cam 5.2 (n=3). Two cases had a history of conventional prostate cancer 4 years before the giant cell component, 1 treated with Lupron and the other with radiation. Follow-up after diagnosis of the giant cell component: Case 1: dead in 1 year of disease; Case 2: progressive metastases in 2 years; Case 3: alive at 1 year with disease; Case 4: large perineal recurrence after brachytherapy at 3 years; Case 5: radical prostatectomy with extraprostatic extension and seminal vesicle invasion; and Case 6: alive at 3 months, free of disease. Conventional prostate cancer, even when very high grade, typically consists of cells with relatively uniform nuclei. Our study expands the histology described in prostate cancer to include in very rare cases with prominent pleomorphism and bizarre giant cells. This giant cell component heralds a particularly aggressive clinical outcome.
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PMID:Pleomorphic giant cell adenocarcinoma of the prostate: report of 6 cases. 1700 Nov 56

Prostaglandin E(2) (PGE(2)), one of the major metabolites of cyclooxygenase-2, has been implicated in tumorigenesis and tumor progression in several human cancers, including colorectal and lung. Here, we show that one of the PGE(2) receptors, the EP4 receptor, plays an important role in metastasis in both of these tumor types. Using i.v. injected Lewis lung carcinoma (3LL), we found that tumor metastasis to lung was significantly reduced when mice were treated with a specific EP4 antagonist ONO-AE3-208 or when EP4 receptor expression was knocked down in the tumor cells using RNA interference technology. Host EP4 receptors also contributed to tumor metastasis and tumor growth with decreased metastasis and tumor growth observed in EP4 receptor knockout animals. In vitro tumor cell adhesion, motility, invasion, colony formation, and Akt phosphorylation were all significantly inhibited when 3LL cells were treated with the EP4 receptor-specific antagonist. When the cells were treated with an EP4-specific agonist (AE1-734), we observed a worsening of these same features in vitro. Treatment with ONO-AE3-208 also profoundly decreased liver metastases after intrasplenic injection of MC26 colon cancer cells. Our data show that selective antagonism of EP4 receptor signaling results in a profound reduction in lung and colon cancer metastasis. Selective antagonism of the EP4 receptor may thus represent a novel therapeutic approach for the treatment of cancer and especially its propensity to metastasize.
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PMID:Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism. 1701 24

The incidence and prognostic significance of micrometastases (Mic-Met) in axillary lymph nodes (LNs) is still controversial. We compared Mic-Met detection of invasive mammary carcinomas (IMCs) in axillary LNs using second review of hematoxylin and eosin (H&E)-stained slides and immunohistochemistry (IHC) relating them with features of the primary tumor, and determining their influence on overall survival (OS) and disease-free survival (DFS). We studied 188 cases of IMCs with no axillary metastases in the initial reports. The original H&E slides of LN were re-viewed and new sections were submitted for IHC using pancytokeratin (AE1/AE3). All primary breast tumors were re-viewed and classified according to Page et al (1998) and College of American Pathologists criteria (2000). Tumors were graded using the Nottingham grading system. Kaplan-Meier curves were used to evaluate OS and DFS of 147 patients. Mic-Met detection was correlated to histologic features of primary tumor (size, type, grade, lymphatic/blood vessel invasion). Mic-Met were detected in 26/188 cases (by IHC: 23/188, 12.2%; by H&E: 12/188, 6.4%). The re-view of H&E slides showed good specificity (98.2%), but low sensitivity (39.1%), when compared with IHC. There was no relationship between features of primary tumor and Mic-Met detection, including patients with lobular carcinomas or IMCs with lobular features. There was no statistical difference in OS and DFS of patients with and without Mic-Met, but patients with Mic-Met presented lower survival curves. In conclusion, there was no relationship between histologic features of primary tumor and presence of Mic-Met, nor between Mic-Met detection and patients survival.
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PMID:Relationship between histologic features of primary breast carcinomas and axillary lymph node micrometastases: Detection and prognostic significance. 1712 40

Squamous cell carcinoma is a rare thyroid neoplasm that has been described exclusively in adults. We report what appears to be the first example of a primary squamous cell carcinoma of the thyroid gland arising in a background of Hashimoto's thyroiditis in an adolescent female. The tumor was well demarcated, confined to the right thyroid lobe, and did not metastasize, although follow up has been limited. The squamous cell carcinoma was well to moderately differentiated, and the stroma contained an abundant inflammatory infiltrate rich in lymphocytes and eosinophils. The lack of goblet cells, extracellular mucin, and extensive stromal sclerosis excluded the diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia. Immunohistochemical staining revealed focal expression of cytokeratin 7 and diffuse labeling with cytokeratin AE1/AE3. The squamous cell carcinoma overexpressed p53 protein and showed increased proliferative activity, as evidenced by the high MIB-1 labeling index. In contrast, the tumor did not show immunoreactivity for thyroglobulin or thyroid transcription factor 1.
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PMID:Primary squamous cell carcinoma of the thyroid arising in Hashimoto's thyroiditis in an adolescent. 1716 93

The purpose of this study was to explore whether detection of disseminated tumor cells (DTCs) in bone marrow (BM) of nonmetastatic prostate cancer (PC) was associated with other clinical or histopathological factors at diagnoses or clinical outcome subsequent to definitive radiotherapy (RT). We evaluated BM aspirates from 272 cT(1-4)pN(0)M(0) PC patients by immunocytochemistry employing anticytokeratin antibodies (AE1/AE3). BM-status was compared with clinical and histopathological parameters. Long-term clinical outcome was assessed in 131 of the patients who all had completed definitive RT with or without androgen deprivation (AD), initiating treatment >5 years before cut-off date June 1, 2005. They had at least 1 unfavorable prognostic feature defined as cT(3-4) or Gleason score (GS) >or= 7B or PSA >or= 10 microg/l. Overall death, cause-specific death, distant metastases (DM) as first clinical relapse, local failure as first clinical relapse and biochemical failure were defined as end-points. DTCs were detected in 18% of the patients and were associated with increasing GS (p = 0.04) and percentage of Gleason pattern 4/5 (p = 0.04). The 7-year cumulative risk of DM was 21% for BM-positive patients vs. 6% for BM-negative patients (p = 0.07). In patients receiving RT without AD (n = 75), the 7-year cumulative risk of DM for BM-positive patients was 28% vs. 9% for BM-negative patients (p = 0.03). BM-status did not have impact on other end-points. In conclusion our study shows that presence of DTCs in BM at diagnosis was associated with the histological differentiation of the primary tumor and an increased risk of developing distant metastases after RT.
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PMID:Impact of disseminated tumor cells in bone marrow at diagnosis in patients with nonmetastatic prostate cancer treated by definitive radiotherapy. 1723 May 12

The aim of this study was to compare immunolabelling of cytological specimens with conventional staining in the detection of metastases in lymph nodes from dogs with carcinoma. Cytological touch imprints of 161 lymph nodes from 72 dogs, as well as 50 fine needle aspirates from 23 dogs, with malignant epithelial tumours were included in the study. Immunolabelling was performed with commercially available human antibodies. Touch imprints of all lymph nodes were labelled with broad spectrum anticytokeratins AE1/AE3 and KL1. In addition, lymph node touch imprints from dogs with primary tumours that reacted positively with the specific anticytokeratins CK7 (n=104) and CK20 (n=20) were also labelled with CK7 and CK20. Fine needle aspirates of 50 lymph nodes were examined by immunolabelling with AE1/AE3. "Reference investigations" with a combination of histological and immunohistochemical methods were performed on all lymph nodes. The immunocytological detection of lymph node metastases with the broad spectrum anti-cytokeratin AE1/AE3 in imprint smears resulted in a significant increase in sensitivity (0.99 vs 0.88 [conventional stain]) and in negative predictive value (0.99 vs 0.85) (P<0.01; t-test). Micrometastases in particular were detected more readily. Specificity (0.93 vs 0.88) and positive predictive value (0.95 vs 0.90) did not differ significantly between the two techniques. Immunolabelling with KL1 was associated with lower sensitivity and negative predictive value, indicating lack of cross-reactivity of this antibody with canine epithelial cells. In fine needle aspirates the detection of lymph node metastases, especially micrometastases, was more efficient by mean of immunolabelling with AE1/AE3 than by conventional staining. The study indicated the value of immunocytological labelling for the detection of metastases in cytological specimens of canine lymph node preparations.
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PMID:Immunocytological detection of lymph node metastases in dogs with malignant epithelial tumours. 1754 25

We report a case of a 60-year-old female with a pigmented microcystic chromophobe renal cell carcinoma (PMCRCC). The tumor was 4.5 cm in diameter, and was located in the right kidney. Grossly, on cross section, the tumor was light gray with multiple small brown to black pigmented foci up to 0.2 cm in diameter. Histologically, the tumor showed a microcystic arrangement with cribriform areas and formation of adenomatous structures. The microcystic and cribriform areas were composed of larger pale cells and smaller eosinophilic cells, with cytological features of conventional chromophobe renal cell carcinoma (CRCC). The cytological features of the cells within the adenomatous structures were different. These cells were mostly columnar with nuclei at the base, and had a variable amount of pale to eosinophilic cytoplasm. There were foci of ample brown pigmentation located in the cytoplasm of the tumor cells and extracellularly. In addition, microscopic calcifications were present. Immunohistochemically, the tumor cells were positive for EMA, E-cadherin, cytokeratin CAM5.2, and cytokeratin AE1/AE3. Cytokeratin 7 was positive only focally. S-100 protein, melan A, HMB 45, vimentin, and CD117 were negative. PMCRCC is a rare tumor. To the best of our knowledge, only one series containing 20 cases of this variant of CRCC has been described to date. The important feature is that PMCRCC seems to have a relatively benign biological behavior, and distant metastases and sarcomatoid transformation are absent.
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PMID:Pigmented microcystic chromophobe renal cell carcinoma. 1765

A 61-year-old man presented with gross hematuria and a polypoid right lateral bladder mass. The tumor was composed of conventional urothelial carcinoma with sarcomatoid and choriocarcinomatous features, both positive for epithelial markers (pancytokeratin, AE1/AE3, and CAM 5.2). In addition, choriocarcinomatous tumor cells were positive for beta human chorionic gonadotropin and placental alkaline phosphatase. Treatments included surgery, chemotherapy, and radiation therapy. The clinical course was aggressive, with liver, lung, and distant lymph node metastases and a postdiagnosis survival of 6 months. This is the first report, to our knowledge, indicating both sarcomatoid and choriocarcinomatous features in a conventional urothelial carcinoma of the bladder.
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PMID:Sarcomatoid urothelial carcinoma with choriocarcinomatous features: first report of an unusual case. 1799 75

Primary myoepithelial tumors of soft tissue are uncommon, and criteria for malignancy among these neoplasms have only recently been established. Of 51 myoepithelial carcinomas of soft tissue in the literature, 11 occurred in children, 7 of which were included in a previous series of myoepithelial tumors from our group. We have collected an additional 22 cases of myoepithelial carcinoma of soft tissue in the pediatric population, and we describe the detailed clinicopathologic features of all 29 cases herein. There were 15 girls and 14 boys; age at diagnosis ranged from newborn to 17 years (median, 9 y). Sites included extremities (14 cases), trunk (6 cases), viscera (5 cases: 3 mediastinal, 1 retroperitoneal, and 1 intracardiac), and head/neck (4 cases). Histologically, the tumors were heterogeneous, with epithelioid, clear, spindle and/or plasmacytoid cells forming nests, cords or solid sheets in a myxoid or hyalinized stroma. Epithelioid cells predominated in the majority of cases (27 of 29; 93%) and in 10 cases (34%), tumor cells focally had scant cytoplasm with round cell morphology. The mitotic rate ranged from <1 to 68 per 10 high power fields (median, 8), and tumor necrosis was present in 14 cases. At least 1 broad-spectrum cytokeratin was positive in all tumors [CAM5.2 in 17 of 18 (94%), AE1/AE3 in 15 of 20 (75%), and PAN-K in 14 of 21 (67%)], and EMA was positive in 19 of 29 cases (66%). Either S100 or GFAP was positive in all but 4 cases [S100 in 21 of 29 (72%) and GFAP in 15 of 28 (54%)]. Clinical follow-up in 23 cases revealed that 9 patients had local recurrences (53% of the 17 patients who underwent complete excision with negative margins); 12 (52%) developed metastases; and 10 (43%) have died of disease so far, at a median interval of 9 months after diagnosis. Despite the relative rarity of carcinomas in the pediatric population, myoepithelial carcinoma seems to be disproportionately common among children and often has an aggressive clinical course.
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PMID:Myoepithelial carcinoma of soft tissue in children: an aggressive neoplasm analyzed in a series of 29 cases. 1804 35


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