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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis is responsible for most deaths from cancer. Currently, little is known about the early genetic events in the metastatic evolution. Here we describe the application of a newly developed strategy for an in-depth characterization of genomic changes in micrometastatic cells. Unique tumor cell lines were established from bone marrow of patients with cancer of the prostate and analyzed by multiplex-FISH (M-FISH) and array CGH. M-FISH revealed that the occult disseminated cells were characterized by very complex numerical and structural aberrations. Many of these aberrations resulted in chromosomal gains and losses, such as losses of 8p, 13q, and 18q and gains of 8q, 9q, 20, and the X chromosome, which are typically observed in prostate cancer. Array CGH allowed an unprecedented high-resolution assessment of copy number changes, pinpointing commonly gained or lost regions, which should narrow down the identification of regions critically involved in metastasis. Thus, occult micrometastatic cells are now amenable to detailed analyses of their genome. Markers for prognosis and treatment decisions can now be established.
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PMID:High-resolution genomic profiling of occult micrometastatic tumor cells. 1250 44

The purpose of this study was to investigate whether Her-2/neu expression at diagnosis of osteosarcoma could provide biologic and prognostic information that predicts the risk of pulmonary metastases and outcome. Human epidermal growth factor (Her-2/neu) expression in 25 initial pretreatment osteosarcoma biopsies and 12 posttreatment pulmonary metastatic osteosarcoma resection specimens was assessed by standard immunohistochemical techniques on formalin-fixed paraffin-embedded tissue. As a screening analysis to determine if gene amplification may be a mechanism for increased Her-2/neu expression, FISH analysis was conducted on seven Her-2/neu immunostain-positive samples and five Her-2/neu immunostain-negative samples. Cytoplasmic Her-2/neu reactivity was identified in 11/25 (44%) of primary tumors and in 7/12 (58%) resection specimens from pulmonary metastases. Cytoplasmic Her-2/neu expression was associated with shorter overall metastasis-free survival. Her-2/neu gene amplification was identified by FISH analysis in six of the seven immunostain-positive samples but was also identified in two of the five immunostain-negative samples. Her-2/neu expression in patients with osteosarcoma is associated with an increased risk of metastasis and may define a subset of patients with a more aggressive tumor phenotype. Her-2/neu gene amplification may provide a mechanism for Her-2/neu overexpression in certain cases of osteosarcoma. Whether Her-2/neu expression influences outcome needs to be examined further in a prospective fashion. The hope is that Her-2/neu expression will identify patients who may benefit from the addition of directed biologic therapy.
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PMID:Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. 1254 70

We report that single agent therapy with trastuzumab had a significant effect on metastatic breast cancer, which was confirmed to be HER2 positive by Herceptest showing 2+staining, and gene amplification positively detected by FISH analysis. A 48-year-old woman underwent extended radical mastectomy (T2N0M0 stage II). Three years after the operation supraclavicular lymph node metastasis was noted. Bone scintigraphy showed metastases to the left ribs 5 years after operation. She was treated with chemo-endocrine therapy, but nonetheless could not bear the back pain caused by the bone metastases. Another chemotherapy course could not be permitted because of leukopenia. Immunohistochemistry (IHC) analysis with Herceptest showed 2+staining for HER2 and FISH analysis showed gene amplification of HER2. We started single agent therapy with trastuzumab and she subsequently had remarkably improved back pain. Physical examination and ultrasonography showed disappearance of the previous palpable supraclaviclar lymph nodes. Serum tumor markers were also reduced after the first administration of trastuzumab. The patient is currently alive, with no further progression of the lymph node or bone metastases.
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PMID:Metastatic breast cancer of HER2 scored 2+ by IHC and HER2 gene amplification assayed by FISH has a good response to single agent therapy with trastuzumab: a case report. 1273 73

Endometrial stromal sarcomas (ESS) are rare neoplasms with the capacity both to invade the myometrium locally and to give rise to extrauterine metastases. Cytogenetic abnormalities have been reported in 22 cases of ESS, mostly involving rearrangements of chromosomes 6, 7, and 17. The most characteristic translocation of this tumor type, t(7;17)(p15 approximately p21;q12 approximately q21), was recently shown to generate a JAZF1/JJAZ1 fusion gene. We report three additional cases of ESS with abnormal karyotypes, whose interpretation was based on the combined analysis by conventional cytogenetics and cross-species color banding FISH (RxFISH). The combination of G-banding and RxFISH in every case gave additional information beyond that obtained by either technique alone, determining the identity of even complex inter- as well as intrachromosomal rearrangements. In one of the three tumors, a t(7;17) was seen; molecular genetic studies identified the JAZF1/JJAZ1 fusion gene in this case. Two tumors had aberrations that included structural changes of chromosome arms 6p and 7p. Evidently, karyotypic, and hence pathogenetic, heterogeneity exists for tumors classified as endometrial stromal sarcomas based on their phenotypic features.
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PMID:Cytogenetic and molecular genetic analyses of endometrial stromal sarcoma: nonrandom involvement of chromosome arms 6p and 7p and confirmation of JAZF1/JJAZ1 gene fusion in t(7;17). 1285 Mar 74

C-erbB-2 (HER2/neu) protein overexpression or amplification has been noted in some solid tumors a molecular target for tumor suppression. C-erbB-2 protein is localized on the membrane surface and is classified in the EGFR family. Trastuzumab is a humanized monoclonal antibody which binds to the extracellular domain of the c-erbB-2 protein in breast cancer cells. Good responders to trastuzumab may be ICH 2 + and FISH positive breast tumors, and ICH 3 + cancer. The response rate is approximately 15% with single administration of trastuzumab. Combination therapy with paclitaxel for the treatment of patients with metastatic cancer may bring more than 60% response and improve time to disease progression. Congestive heart failure associated with trastuzumab may be severe, and combination therapy which includes anthracyclines increases the incidence and severity of cardiac dysfunction. Other toxicities include infusion reaction.
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PMID:[Clinical implications of trastuzumab]. 1293 63

Intratumoral genomic heterogeneity, which can be defined as both intersample and intrasample heterogeneity, is still a poorly understood phenomenon in head and neck squamous cell carcinoma (HNSCC) with presumed implications on tumor behavior and even prognosis. We analyzed 89 tumor specimen from 37 HNSCC patients by fluorescence in situ hybridization (dual-FISH) using specific DNA probes binding to centromeric sites of 6 chromosomes to investigate intratumoral heterogeneity. A derivation from disomy in at least 1/6 chromosomes was detected in 88/89 (99%) specimen. In 33% of these samples, a change in ploidy could be suspected. Intrasample heterogeneity was detected in 68/89 (76%). Intrasample heterogeneity was more pronounced in primary tumors than in metastatic tumors. Analysis of the intersample heterogeneity revealed notable differences between the 6 chromosomes with the highest discordance detected for chromosome 3 (46%) and the lowest for chromosome 11 (27%). Following our results, it seems important to us to underline that intratumoral heterogeneity exists as intra- and sample heterogeneity in HNSCC. Altogether, trisomic cells were significantly more frequent in primary tumors than in metastases (p=0.01) while, in turn, monosomic cells were significantly more frequent in metastases (p=0.029). In individual cases the extent of discordance between corresponding samples made a common clonal precursor unlikely. In these cases, the synchronous development of a primary tumor and a carcinoma of unknown primary ('CUP syndrome'), otherwise undetected, should be considered.
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PMID:Intratumoral genomic heterogeneity in primary head and neck cancer and corresponding metastases detected by dual-FISH. 1465 97

The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.
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PMID:HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review. 1515 May 68

We performed comparative genomic hybridization (CGH) on 8 formalin-fixed, paraffin wax-embedded primary spermatocytic seminomas (SS) from 7 patients, one of whom developed metastatic disease. In general, this tumour type is not associated with development of metastases. Since there are only few reported cases of metastatic SS in the literature, this study is the first report of chromosomal constitution in a patient with metastatic disease. Chromosomal imbalances were observed in all 8 tumours analysed by CGH. Frequent copy number alterations were enh(9), dim(16 or 16p), enh(20) and enh(X), each in 6 samples, followed by dim(7) in 4, and enh(1), enh(18) and dim(15), each in 3 samples. In addition to the CGH analysis, interphase fluorescence in situ hybridisation (I-FISH) was applied to evaluate the CGH results and to define the size of the aberrant cell population. Interphase cytogenetics showed gain of material on chromosomes 9 and X in all tumours analysed. Overall, the I-FISH results were in agreement with the CGH data. In conclusion, gain of chromosome 9 seems to be restricted to SS and point to an important role for this aberration in the development of this tumour type.
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PMID:Molecular cytogenetic analysis of human spermatocytic seminomas. 1547 69

The treatment options for synovial sarcoma (SS) are very limited, though this type of sarcoma seems to be more heterogeneous than it has been traditionally considered. The present study investigates the Her-2 oncogene status of 20 cases of SS, to determine whether Her-2 amplification can be considered as a prognostic factor. Her-2 oncogene amplification was determined on smears (frozen material was used from our tumor bank in each case), using fluorescence in situ hybridization technique (dual color FISH with centromeric probe for chromosome 17 and specific probe for Her-2 oncogene). Moreover, protein expression was assessed by immunohistochemistry, and DNA ploidy status was measured using image analysis. We had 5 biphasic and 15 monophasic SSs, patients' age ranged from 13 to 68 years (mean, 39.8 years). Tumor size was larger than 5 cm in each case. Follow-up time ranged from 6 to 78 months (mean, 38.5 months). For statistical analysis the chi-square test was used. Her-2 oncogene amplification was found in three cases (15.0%) of 20 SSs. These cases proved to be 2+ positive by immunohistochemistry, but massive amplification, characteristic of a subset of breast carcinomas, was not observed. Her-2 oncogene amplification was significantly associated with a lower risk of developing metastasis (P<0.05) (none of the 3 amplified cases had metastases), while no association was found with recurrence. Six cases proved to be aneuploid and 14 were diploid, but no association was found between Her-2 amplification status and ploidy, and between ploidy status and metastasis or recurrence. Our results emphasize and confirm that Her-2 oncogene amplification is a rare event in SS, but the small subset of SS with Her-2 amplification has a better overall prognosis. Furthermore, this may open a theoretically new treatment possibility with Trastuzumab for Her-2-amplified cases of SS.
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PMID:Her-2 oncogene amplification, chromosome 17 and DNA ploidy status in synovial sarcoma. 1619 66

Inflammatory pseudotumor or pseudosarcomatous fibromyxoid tumor and postoperative spindle cell nodule of the bladder are unusual lesions of uncertain pathogenesis which share overlapping, if not identical, histologic features. We present our experience with 42 cases, the largest series to date, to study the etio-pathogenesis, histologic features, biologic behavior and relationship to "inflammatory myofibroblastic tumor" of childhood. Patients ranged in age from 7 to 77 years (mean 47 y) and males predominated (3.2:1). Most patients presented with hematuria (31/42). Common associations were smoking (10/30) and previous instrumentation or surgery (9/42). The clinicopathologic features of patients having or not having prior instrumentation were identical. Grossly the lesions were polypoid or nodular and involved any portion of bladder wall, most commonly the dome (9/27) and measured 1 to 10 cm (mean 4 cm). They were composed of spindled and stellate cells arranged in a myxoid background with numerous inflammatory cells. Myxoid hypocellular areas were more pronounced near the mucosal surface with greater cellularity and a fascicular arrangement in the deep aspect of the lesion. "Atypical" features included mitotic activity (0 to 20/10 HPF; mean 2/10 HPF; median 1/10 HPF; none atypical), necrosis (22/42), and extension into muscularis propria (28/32) or perivesicular fat (3/8). Lesions were positive for cytokeratin (31/33), SMA (23/34), desmin (21/35), and Alk-1 protein (12/26). FISH confirmed the Alk-1 translocation in 4/6 cases. Treatment included transurethral resection (30/42), partial cystectomy (9/42), and total cystectomy (3/42). Initial diagnostic error resulted in radiotherapy and chemotherapy in 3 patients. Follow-up was available in 28 patients. (range 3 to 93 mo; median 25 mo). Three patients developed recurrences, but none had metastases. Because the clinicopathologic features of lesions associated with and without instrumentation were similar and inseparable, we believe they are essentially the same entity, and propose the term pseudosarcomatous myofibroblastic proliferation. The preponderance of evidence which includes the extravesical growth, local recurrence, and Alk-1 gene translocation in some cases suggests perhaps a neoplastic process with limited growth potential. Even in the face of atypical histologic features (muscle invasion and necrosis) the prognosis is excellent. Despite the Alk-1 gene translocation, there continues to be sufficient evidence for regarding these as distinct from the so-called inflammatory myofibroblastic tumor of childhood.
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PMID:Pseudosarcomatous myofibroblastic proliferations of the bladder: a clinicopathologic study of 42 cases. 1741 15


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