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)

The aim of this study was to evaluate the clinical utility of immunohistochemical staining of human testicular germ cell tumours with the monoclonal antibody 43-9F to distinguish embryonal carcinoma (EC) from other malignant germ cell components in order to facilitate pathohistological assessment of prognostic risk factors for metastatic disease in clinical stage I NSGCT. Archival, formalin-fixed, paraffin-embedded tissue blocks of 24 classical seminomas, 7 spermatocytic seminomas, and 20 non-seminomatous germ cell tumours were stained for 43-9F, AFP, hCG and PLAP expression. Immunohistochemical expression was graded using a semi-quantitative scoring system: 1+ = 0-25%, 2+ = 26-50%, 3+ = 51-75% and 4+ = 76-100%. Positive immunohistochemical staining for 43-9F was found in all embryonal carcinomas and yolk sac tumours (YST); staining intensity was not statistically different between the two tumours (3.8 +/- 1.2 vs. 3.1 +/- 0.9). Classical seminomas and seminomatous components of NSGCT stained positive in 13/24 cases (54%); staining intensity was weak to moderate (1.1 +/- 0.7) in all but two cases (4+). Spermatocytic seminomas demonstrated weak positive immunostaining in 2/7 cases (29%). Adjacent CIS was found in 33/54 (61.1%) of tumours and 24/33 (72.7%) of CIS cells exhibited a weak to moderate staining intensity (1.4 +/- 0.7). AFP expression was found in 93% of YST and in only 10% of EC; however, based on the focal staining pattern, adequate differentiation of YST and EC was not possible. Positive PLAP staining was observed in 75% of EC, 79% of seminomas and in 88% of CIS cells. We did not find 43-9F staining clinically useful to distinguish embryonal carcinoma from other germ cell tumour components such as yolk sac tumour. The detection rate of CIS by 43-9F immunohistochemical staining was low and combination of PLAP staining with light microscopy was even superior. Additionally, our study confirms the link between pre-invasive CIS and embryonal carcinoma and suggests the possible direct development of embryonal carcinoma from CIS.
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PMID:Immunohistochemical expression of monoclonal antibody 43-9F in testicular germ cell tumours. 980 44

Aim of this review article was to critically analyse the recently described zytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosome i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (Cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromsomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in research for prognosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it also will define new approaches to classification and management of germ cell tumors.
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PMID:[Molecular pathogenesis and prognostic factors in testicular tumor]. 988 88

Since June 1993, unilateral laparoscopic retroperitoneal lymph-node dissection (LRPLND) has been performed in six patients with clinical Stage I nonseminomatous germ-cell tumors (NSGCT). All of the patients had undergone prior radical orchiectomy. The testicular cancer was left-sided in three cases and right-sided in three cases. Preoperative staging by means of tumor marker assessment, CT scan of the chest and abdomen, and chest radiography was unremarkable for metastatic disease. All procedures were accomplished without any complications in a mean time of 325 minutes (275-420 minutes). The estimated perioperative and postoperative blood loss was minimal, and none of the patients required blood transfusion. In the case of the first patient, the hospital stay was 18 days because of a widespread subcutaneous emphysema. In the remaining five cases, the average hospitalization was 4.8 days (range 4-6 days). The patients resumed normal activities within 12 to 27 days (mean 16.16 days) postoperatively. The mean number of lymph nodes removed was 6.8 (range 5-9). Histologic examination of these nodes revealed microscopic metastases from embryonal carcinoma in two patients, both of whom were subjected to adjuvant chemotherapy. The mean follow-up period is 27.1 months (range 12-42 months). To date, no relapses have been observed. In accordance with other reports, we believe that LRPLND is both feasible and effective. However, larger and more comprehensive studies with long-term follow-up are required to determine whether this approach is reliable and definitely superior to standard open surgery in the management of clinical Stage I NSGCT.
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PMID:Unilateral laparoscopic retroperitoneal lymphadenectomy for clinical stage I nonseminomatous testicular cancer. 989 63

Teratocarcinoma is a mixed germ cell tumor histologically composed of embryonal carcinoma cells and embryonic and extraembryonic tissues. In the present work we have used the CE44 teratocarcinoma, which is a tumor cell line derived from the OTT6050 experimental tumor, to appreciate the influence the microenvironment has on the modulation of tumoral differentiation. For this, we have studied the development of CE44 teratocarcinoma in primary tumors (subcutaneous and intrasplenic) and in experimental metastases (hepatic and pulmonary). CE44 teratocarcinoma shows variations in its capacity for differentiation in so far as development is concerned and, in hepatic metastases, we noticed a reparative process of the intratumoral necrotic areas which in the same cases were substituted by loose connective tissue. Our results clearly suggest that the microenvironment is decisive in the biological behaviour of the teratocarcinoma cells and that epigenetic factors influence the capacity for differentiation of the undifferentiated tumoral cells.
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PMID:Epigenetic modulation of differentiation in CE44 teratocarcinoma. 998 44

This is a report of successful management for a far advanced, chemorefractory testicular cancer patient. A 29-year-old male was referred to our hospital for the treatment of progressive lung metastases with elevated hCG level, which had recurred after complete remission following 3 courses of BEP chemotherapy and progressed after transient partial regression following 2 courses of intensified EP chemotherapy. In addition, a 3 cm in diameter, solitary brain metastasis was detected on CT. First, we performed wedge resection of bilateral pulmonary lower lobe for chemorefractory pulmonary metastases. Histological examination revealed viable embryonal carcinoma identical to the primary one. Thereafter, whole brain irradiation in combination with VIP chemotherapy (etoposide 100 mg/m2, cisplatin 20 mg/m2 and ifosfamide 1200 mg/m2 daily for 5 consecutive days) was carried out to treat brain metastasis. By 2 cycles of VIP therapy and irradiation (36 Gy), partial tumor regression and normalization of hCG level were achieved, leading to salvage surgery of the brain metastasis which histologically proved to be necrosis. Following an additional cycle of VIP therapy, the patient has been free of recurrence 24 months after completion of the treatment.
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PMID:[Successful management for chemorefractory testicular cancer with brain and lung metastases. A case report]. 999 Feb 29

Purpose of our study was to develop a reliable model to define clinical stage I nonseminomatous germ cell tumors (NSGCT) being at low risk and at high risk for occult retroperitoneal metastases based on pathohistological and immunohistochemical parameters in order to stratify the therapeutic approach. 3-5 paraffin-embedded formalin fixed tissue blocks of 149 clinical stage I NSGCT were available from all patients and were analyzed for histopathological features associated with pathological stage: presence/absence of vascular invasion, presence/absence of tunical invasion, percentage of each histological cell type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D and e-cadherin was evaluated using a semiquantitative scoring ystem. Statistical analysis was performed by univariate and multivariate logistic regression models. Percentage of embryonal carcinoma [%EC (p < 0.001)] and presence of vascular invasion [VI (p < 0.0001)] were the most significant independent risk factors associated with pathological stage II disease. Combination of %EC and VI allowed correct prediction of final pathological stage in 88% of patients. Cut-off values including both variables identified correct pathological stage in 131/149 patients (88%). Less than 45% EC and absence of VI correctly identified pathological stage I disease in 91.5%; more than 80% EC and presence of VI correctly predicted pathological stage II in 88% of the patients. %EC and presence/absence of VI appear to be reliable prognosticators to identify both patients at high risk and at low risk for occult retroperitoneal disease. P53, bcl-2, MIB-1, cathepsin D and e-cadherin did not appear to be of prognostic value in clinical stage I NSGCT.
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PMID:[Histopathologic and biological prognostic factors of clinical stage I non-seminomatous germ cell tumors. Implications for risk-adjusted therapy]. 1023 39

The classic testicular tumor marker alpha-fetoprotein (AFP) is associated with nonseminomatous germ cell tumors, including embryonal carcinoma, yolk sac tumor, and teratoma. AFP is not considered to be produced by pure seminoma. However, postmortem studies have demonstrated that 30 to 45% of patients who died of seminoma initially diagnosed harbored nonseminomatous metastases and had an elevated serum AFP. We analyzed AFP expression by immunohistochemistry and by nested reverse transcription-polymerase chain reaction (RT-PCR) in 10 seminomas, 3 embryonal carcinomas, and 1 immature teratoma, diagnosed by traditional clinical methods. Positive immunohistochemical staining was observed in all embryonal carcinomas and in the teratoma but not in the seminomas. AFP mRNA, however, was found in 6 of 10 seminomas, in all embryonal carcinomas, and in the teratoma. The nucleotide sequence of PCR products was identical with that of the AFP gene. We conclude that the analysis of AFP gene expression by nested RT-PCR would be useful for detecting minute quantities of nonseminomatous germ cell elements in classic seminoma. Moreover, the existence of AFP mRNA suggests the possibility that seminoma cells can differentiate into nonseminomatous germ cells.
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PMID:Detection of alpha-fetoprotein mRNA in seminoma. 1038 12

Risk factor analysis to identify low-risk patients for occult metastatic disease (vascular invasion, percentage embryonal carcinoma, MIB-I proliferation rate) yields reliable results if performed by experts. A correct prediction is possible at the 90% level. Similar accuracy, however, may be achieved if the computed tomography (CT) staging is optimized and the evaluation performed by an experienced investigator. The combination of both methods (biological risk factor analysis and CT staging) may virtually exclude the risk of relapse in a limited number of patients. However, so far, no risk factor that is able to reliably predict occult metastatic disease or relapse in clinical state I patients has been identified in prospective trials. The preliminary results of the current German Multicenter Trial suggest an inferior value of prediction for low-risk patients if risk factor analysis and/or CT staging is performed in non-specialized centers.
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PMID:Risk factors for relapse in stage I non-seminomatous germ-cell tumors: preliminary results of the German Multicenter Trial. German Testicular Cancer Study Group. 1059 3

Improvements in the clinical staging of testicular cancer may permit the identification of clinical stage I patients at low risk of harboring metastatic disease, who could be spared treatment and observed only. Both retrospective, single-institution studies and studies of unselected, consecutive patients have confirmed that vascular invasion, lymphatic invasion, and percentage of embryonal carcinoma are predictive of metastasis in patients with low-stage nonseminoma. Whether patients with these risk factors have a worse outcome if managed with surveillance, rather than with aggressive therapy, is unclear. Low MIB-1 staining (which identifies the Ki-67 antigen) in conjunction with a low percentage of embryonal carcinoma in the testicular specimen appears to be predictive of a low probability of metastasis. Computed tomography (CT) is a useful staging tool. A new prognostic classification system for seminomas and nonseminomas was recently developed by an international consensus conference. Laparoscopic retroperitoneal lymphadenectomy appears to be a feasible staging tool with acceptable short-term morbidity. Whether laparoscopic lymph node dissection is equivalent to the open procedure when used as a therapeutic modality is not yet known. At present, laparoscopy should be used only in selected patients in a study setting. Primary chemotherapy is not recommended currently because it has not yet been proven to be superior in patients with high-risk clinical stage I nonseminoma and can cause significant long-term sequelae.
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PMID:Testicular cancer: what's new in staging, prognosis, and therapy. 1063 1

Aim of this review article was to critically analyze the recently described cytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosme i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromosomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies the percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in the research for prgnosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it will also define new approaches to classification and management of germ cell tumors
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PMID:Molecular genetic parameters in pathogenesis and prognosis of testicular germ cell tumors. 1070 88


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