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Germ Cell Tumors (germ + cell_tumor)
Kinds of Germ Cell Tumors Selected AbstractsHERV-K(HML-2) GAG/ENV antibodies as indicator for therapy effect in patients with germ cell tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2004Anna Kleiman Abstract Germ cell tumors (GCT) are strictly associated with the expression of HERV-K(HML-2) proviruses, and the majority of GCT patients produce antibodies to structural proteins of these proviruses. The objective of our study was to determine the significance of the serological response to HERV-K(HML-2) Gag and Env proteins for diagnosis, management of GCT patients and estimation of the therapy success. The data document a strong association of HERV-K(HML-2) antibodies and the clinical manifestation of the disease and therapy success. HERV-K(HML-2) antibodies seem to have an important diagnostic value as well as indicator of chemotherapy success. © 2004 Wiley-Liss, Inc. [source] Twist is inversely associated with claudins in germ cell tumors of the testisAPMIS, Issue 9 2010PÄIVI VÄRE Väre P, Soini Y. Twist is inversely associated with claudins in germ cell tumors of the testis. APMIS 2010; 118: 640,7. We investigated the expression of claudins 1, 3,7 and transcriptional factor twist in a set of testicular germ cell tumors. The material consisted of 17 seminomas, 13 teratomas, 9 teratocarcinomas, 20 embryonal carcinomas and 9 mixed germ cell tumors. They were immunostained with antibodies to claudins 1, 3,7 and twist. As expected, all claudins were variably present in germ cell tumors with epithelial elements or differentiation, but the intensity of expression varied depending on the claudin type. Mesenchymal elements in teratomatous tumors remained negative for claudins. Expression of different claudins was less intense and inconsistent in other types of germ cell tumors. Choriocarcinomatous elements in germ cell tumors expressed relatively strongly claudin 4 and weaker positivity for claudins 5,7, while claudins 1 and 3 were negative. Seminomas showed expression only for claudins 5 and 7. The transcriptional factor twist was most strongly expressed in seminoma followed by embryonal carcinoma. Twist expression was inversely associated with several claudins (claudins 1, 3, 4 and 6). Germ cell tumors vary in their expression of claudins 1,7. Twist expression was inversely associated with several claudins, suggesting that it takes part in the downregulation of claudins in testicular tumors. [source] Aspiration biopsy cytomorphology of primary pulmonary germ cell tumor metastatic to the brainDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2009Haitham Arabi M.D. Abstract Extragonadal germ cell tumors are uncommon and such tumors originating from the lung parenchyma are extremely rare. This is a case of 68-year-old female who was admitted with complaints of right-sided weakness, inability to maintain her balance, right-sided headache, and bloody sputum. Her workup revealed two enhancing brain lesions and large lung mass involving the left lower lobe. Fine-needle aspiration (FNA) of the lung followed by craniotomy was performed and the patient was initially diagnosed with lung adenocarcinoma metastatic to the brain based on the cytomorphology of the lung FNA and histology of the brain mass. However, retrospective investigation revealed markedly elevated alpha fetoprotein (AFP) of which the cytopathologist was unaware at the time of diagnosis. A review of the cytology and surgical specimen slides, as well as immunohistochemistry (IHC) on the brain tumor and FNA cell block were preformed. On the basis of the slides review, clinical findings, and immunostaining results, a diagnosis of primary pulmonary mixed germ cell tumor, containing choriocarcinoma and yolk sac elements, with brain metastases, was retrospectively made. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Cerebral hemiatrophy with superficial siderosis and PLEDs due to a germ cell tumor of the basal gangliaEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2006N. Kumar The diagnosis of basal ganglia germ cell tumors may be delayed due to slow progression and minimal early changes on magnetic resonance imaging (MRI). The cystic nature of some tumors may lead to non-diagnostic biopsies. We describe the clinical, imaging, laboratory, and postmortem findings of a basal ganglia germ cell tumor in a 19-year-old man. Clues to an early antemortem diagnosis based on MRI findings and determination of tumor markers are discussed. An early diagnosis and accurate characterization of basal ganglia germ cell tumors is essential for optimal therapy. The presence of cerebral hemiatrophy and hemorrhagic or cystic components is suggestive. Measurement of serum and cerebrospinal fluid markers such as human chorionic gonadotropin may suggest the diagnosis. [source] High-resolution comparative genomic hybridization detects extra chromosome arm 12p material in most cases of carcinoma in situ adjacent to overt germ cell tumors, but not before the invasive tumor developmentGENES, CHROMOSOMES AND CANCER, Issue 2 2003Anne Marie Ottesen High-resolution comparative genomic hybridization (HR-CGH) analysis was performed on DNA purified from laser-capture microdissected carcinoma in situ (CIS) cells from nine cases of CIS, either from tissue without any invasive tumor or from testicular parenchyma adjacent to seminoma, nonseminoma, or a combined germ cell tumor. Before CGH analysis, DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and directly labeled with a mixture of FITC-dUTP and FITC-dCTP. CGH analysis revealed extra chromosome arm 12p material in six out of seven cases with CIS adjacent to overt tumors, but only a diminutive gain of 12q was noted in one of the two cases of CIS without invasive elements. In addition, gains of parts of chromosome 8 (3/7) and losses of chromosome 5 (2/7) were demonstrated in CIS adjacent to invasive tumors. Gains of parts of chromosome 7 were found in CIS adjacent to seminoma (4/4), whereas relative gains of chromosome 15 were identified in some cases of CIS adjacent to seminoma and in isolated CIS in comparison to CIS adjacent to nonseminoma. Our data seem to indicate that extra 12p material is not present in the "dormant" CIS cell before development of an invasive tumor. The gain of extra chromosome 12 material may not be an early event in the neoplastic transformation, but is most likely associated with a more malignant progression of the CIS cell. © 2003 Wiley-Liss, Inc. [source] Incorporation of TIP (paclitaxel, ifosfamide, cisplatin) into first-line therapy for intermediate to poor risk testicular germ cell tumors with unfavorable marker decline after initial two cycles chemotherapy: A report of three casesINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2007Jun-Ichiro Ishioka Abstract: Three patients of advanced-non-seminomatous germ cell tumors (International Germ Cell Cancer Collaborative Group classification: poor risk, 2; intermediate, 1) without evidence of a second primary germ cell tumor were treated. The patients received two cycles of standard BEP (bleomycin, etopside, cisplatin) or VIP/VB (etoposide, ifosphamide, cisplatin/vinblastine, bleomycin) therapy first. All patients in this trial showed unfavorable marker response to these therapies and received four cycles of TIP subsequently. A complete remission was observed in all patients. No patient experienced life-threatening toxicity. During the 34-month observation period, all patients were alive without progression. [source] High-dose chemotherapy for male germ cell tumorINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2006ISAO HARA Abstract, Today, 20,30% of male patients with advanced germ cell tumor (GCT) do not have durable, complete remission in spite of cis -platinum (CDDP)-based chemotherapy. High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients. Initially HDCT was performed with autologous bone marrow transplantation in heavily treated patients. However, the clinical outcome was not good and the treatment-related death rate was not ignorable. Therefore, earlier introduction of HDCT with peripheral blood stem cell transplantation was preferable as it renders HDCT more effective and less toxic, and multicycle HDCT is feasible. The durable free rate of recent HDCT for refractory GCT patients is 32,65%. HDCT is also performed as first line chemotherapy for poor prognosis GCT patients. Induction chemotherapy followed by multicycles of HDCT was tried. The durable free rate of recent HDCT as first line chemotherapy is 43,73%. Although previous reports suggest the superiority of HDCT, one recent randomized controlled trial (RCT) failed to show an improvement with one cycle of HDCT followed by three cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT. Ongoing RCT comparing multicycles of HDCT with SDCT for poor prognostic GCT patients will clarify the role of HDCT. Recently, new regimens of HDCT containing paclitaxel have been devised. In this review, the history, current status and future of HDCT for advanced or refractory GCT will be discussed. [source] Retroperitoneal seminoma with ,burned out' phenomenon in the testisINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2005PETROS PERIMENIS Abstract The rare ,burned out' phenomenon in germ cell tumors is known as the presence of an extragonadal germ cell tumor without traces of neoplasm in the testis. This condition is different and less common from the primary extragonadal germ cell malignancies. These malignancies are treated surgically with or without adjuvant chemotherapy or radiotherapy and their prognosis is better than that of other types of primary extragonadal tumors. [source] Case of mediastinal seminoma with testicular microlithiasisINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2002Koji Sato Abstract Testicular microlithiasis is a rare condition in which calcified concretions fill the lumina of the seminiferous tubules. We report the case of a 19-year-old Japanese man with mediastinal seminoma, normal testicular physical findings and bilateral testicular microlithiasis seen on ultrasonography. Testicular needle biopsy demonstrated multiple laminated calcifications within the seminiferous tubules without any signals of a viable germ cell tumor. To our knowledge, this is only the sixth reported case of extragonadal germ cell tumor with testicular microlithiasis. [source] Testis sparing surgery for the treatment of a sequential bilateral testicular germ cell tumorINTERNATIONAL JOURNAL OF UROLOGY, Issue 12 2001ZIYA KIRKALI Abstract Standard therapy of sequential bilateral testis cancer is generally considered to be orchiectomy. We present a case of sequential bilateral testicular germ cell tumor treated with testis sparing surgery. The patient was disease free 50 months after surgery without local recurrence or distant metastases. Testis sparing surgery provides a better quality of life and may be considered a safe, feasible alternative in the treatment of carefully selected patients with bilateral testicular germ cell tumor. [source] Fertility-preserving treatment for patients with malignant germ cell tumors of the ovaryJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2006Shin Nishio Abstract Aim:, The aim of this study was to investigate whether fertility preservation influences the clinical outcome in patients with malignant germ cell tumors of the ovary (MGCTO). Methods:, A case study analysis was performed on patients with MGCTO treated at Kurume University Hospital between 1986 and 2004. Thirty-five patients were included in the study, 14 with immature teratoma, 11 with dysgerminoma, eight with endodermal sinus tumor, and two with mixed germ cell tumor. Twenty-three patients had International Federation of Gynecology and Obstetrics stage I (Ia, 11; Ib, 2; Ic, 10), one had stage II, seven had stage III, and four had stage IV disease. Results:, Five patients with stage III or IV disease received radical surgery. Thirty patients underwent conservative surgery. As the adjuvant treatment, 30 patients received chemotherapy, while five patients did not receive any chemotherapy. The overall survival rate was 97.1%. One patient died of the disease. She was 13 years old with a stage IV endodermal sinus tumor. Twelve have attempted conception, and eight have achieved at least one pregnancy (66.7%). Conclusions:, Irrespective of the stage of the disease, conservative surgery and adjuvant chemotherapy for MGCTO can achieve a favorable outcome in terms of survival and fertility. [source] Alpha-fetoprotein producing uterine corpus carcinoma: A hepatoid adenocarcinoma of the endometriumPATHOLOGY INTERNATIONAL, Issue 10 2000Hiroshi Toyoda A case of alpha-fetoprotein (AFP) producing endometrial carcinoma in a 60-year-old Japanese woman is presented. The patient complained of abnormal vaginal bleeding of 10 days' duration. On admission a uterine corpus mass and high serum AFP concentration (31950 ng/mL) was noted. There was no tumorous lesion in any other organ radiographically and endoscopically. Histologically, the biopsy specimen taken from the uterine mass showed a poorly differentiated endometrial carcinoma and a radical hysterectomy was subsequently performed. The postoperative serum AFP value transiently decreased with chemotherapy, however, lung metastases were found and the patient died 12 months following surgery. The resected uterus had a necrotic tumor, 6 × 5 × 4 cm in size, filling the endometrial cavity, characterized by exophytic growth with infiltration in the myometrium. Histologically, the tumor was composed of the main medullary carcinoma area with microcysts and admixed small areas of well-differentiated endometrioid adenocarcinoma, accompanied by a smooth transition with one another. In both the areas, the tumor cells had immunoreactive AFP, alpha-1-antitripsin, albumin, transferrin, carcinoembryonic antigen, CA19-9, and epithelial membrane antigen. There was no histologic evidence for a germ cell tumor. Based on these findings, this uterine corpus tumor was regarded as hepatoid variant of endometrial carcinoma. Although the histogenesis remains controversial, we assume the hypothesis that the tumor may arise in the endometrium per se in association with abnormal differentiation of muellerian duct elements. [source] Curative pulmonary metastasectomy for non-seminomatous germ cell tumor of the testisANZ JOURNAL OF SURGERY, Issue 5 2010MBBS, Terence C. Chua BScMed (Hons) No abstract is available for this article. [source] Long-term outcome for men with teratoma found at postchemotherapy retroperitoneal lymph node dissection,CANCER, Issue 6 2009Robert S. Svatek MD Abstract BACKGROUND: Patients with pure teratoma within the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been considered at low risk for disease progression. The objectives of this study were to determine the disease-related outcomes of patients who had pure teratoma identified at the time of PC-RPLND and to examine the prognostic value of clinical variables that were identified previously as important predictors of disease recurrence in these patients. METHODS: Between 1980 and 2003, 97 patients with metastatic nonseminomatous germ cell tumor and pure teratoma histology at the time of PC-RPLND were identified. The medical records of these patients were reviewed retrospectively for pertinent clinical and treatment-related outcomes. RESULTS: At a median follow-up of 7.4 years, 21 patients (22%) developed recurrent disease after PC-RPLND. The 5-year and 10-year probabilities (±standard error) of freedom from disease recurrence were 81% ± 4% and 76% ± 5%, respectively. The postchemotherapy ,-fetoprotein (AFP) level and mediastinal involvement at presentation were statistically significant predictors of disease recurrence on multivariate analysis. Nine of 97 patients (9.3%) died from testis cancer, and 4 patients died from other causes. CONCLUSIONS: In patients with pure teratoma histology at PC-RPLND, mediastinal involvement at presentation and the presence of an elevated AFP level before PC-RPLND predicted an unfavorable outcome. The absence of mediastinal involvement and normal AFP level, however, did not confirm freedom from disease recurrence. Patients who had teratoma at the time of PC-RPLND remained at considerable risk for disease progression because of the unpredictable nature of teratoma and the presence of unrecognized, active germ cell disease outside the retroperitoneum. Cancer 2009. © 2009 American Cancer Society. [source] Viable germ cell tumor at postchemotherapy retroperitoneal lymph node dissection,CANCER, Issue 12 2007Can we predict patients at risk of disease progression? Abstract BACKGROUND. Patients with viable tumor at time of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) are at an increased risk of disease progression. The objective of the current study was to determine the clinical variables that predict this adverse outcome. METHODS. Between 1980 and 2003, 236 patients with testicular cancer underwent PC-RPLND, 41 of whom (17%) were found to have viable tumor. The authors retrospectively reviewed the patients' medical records for pertinent clinical and treatment-related outcomes. At a median follow-up of 3.9 years, 18 patients (44%) had developed disease recurrence and 12 patients (29%) had died of disease. RESULTS. The group of patients who developed postoperative disease recurrence had a larger median dimension of the retroperitoneal mass (7.0 cm and 3.5 cm, respectively; P = .03). The use of adjuvant chemotherapy after PC-RPLND was less common in those patients developing postoperative disease recurrence (P = .06). On multivariate analysis, patients classified as being at intermediate or poor risk according to the International Germ Cell Consensus Classification (IGCCC) had a poorer recurrence-free survival (P = .006 and P = .07, respectively). On multivariate analysis, predictors of disease-specific survival (DSS) included an elevated ,,fetoprotein (AFP) level before PC-RPLND (P = .003) and postoperative disease recurrence (P = .02). A serum AFP level >5.3 ng/mL before PC-RPLND was found to be predictive of a poorer DSS (P = .0007). CONCLUSIONS. Patients with viable tumor at the time of PC-RPLND are at an increased risk of disease progression. Clinical variables including classification as intermediate or poor IGCCC risk, a preoperative serum AFP level >5.3 ng/mL, and postoperative disease recurrence help to better define those patients who are at risk of future adverse outcomes. Cancer 2007. © 2007 American Cancer Society. [source] Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinomaCANCER, Issue 10 2005Uche I. Ezeh M.D. Abstract BACKGROUND The seminoma class of testicular germ cell tumor (TGCT) are characterized by a morphological resemblance to primordial germ cells (PGCs) or gonocytes, and chromosome duplications at 12p. Recently, it was determined that human embryonic stem cells (hESCs) express genes in common with PGCs, and that three of these genes, GDF3, STELLAR, and NANOG, are located on 12p. The current study was designed to identify whether expression of these 12p genes were elevated in seminoma relative to normal testis, and to determine whether elevated expression was unique to seminoma. METHODS Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to assess gene expression in seminoma samples relative to normal testis and endpoint PCR was used to identify the presence or absence of these genes in breast carcinoma. RESULTS GDF3 expression was increased in eight of nine seminomas compared with normal testis, whereas NANOG, OCT4, or both were expressed at the highest levels in seminoma compared with all other markers analyzed. In addition, the NANOG protein was expressed in the majority of seminoma cells. The adult meiotic germ cell markers BOULE and TEKT1 were undetectable in seminoma, whereas the embryonic and adult germ cell markers DAZL and VASA were significantly reduced. Analysis of these markers in breast carcinoma and the MCF7 breast carcinoma cell line revealed that a core hESC-transcriptional profile could be identified consisting of OCT4, NANOG, STELLAR, and GDF3 and that NANOG protein could be detected in breast carcinoma. CONCLUSIONS These observations suggest that seminoma and breast carcinoma express a common stem cell profile and that the expression of DAZL and VASA in seminoma mark the germ cell origin of seminoma that is absent in breast carcinoma. Our findings suggest that stem cell genes may either play a direct role in different types of carcinoma progression or serve as valuable markers of tumorigenesis. Cancer 2005. © 2005 American Cancer Society. [source] Does retroperitoneal lymph node dissection have a curative role for patients with sex cord,stromal testicular tumors?CANCER, Issue 4 2003Ashraf A. Mosharafa M.D. Abstract BACKGROUND Sex cord,stromal tumors account for < 5% of all adult testicular tumors, and 10% are malignant. Due to the limited reported experience, there is no agreement on the best management, especially in patients who have tumors with malignant pathologic features or who present with metastatic disease. The authors attempt to evaluate the role of retroperitoneal lymph node dissection (RPLND) in the management of patients with these malignant sex cord,stromal tumors. METHODS Reviewing the Indiana University testis cancer registry revealed 17 patients who underwent RPLND for sex cord,stromal tumors. Pathology was reviewed for features suggestive of malignancy. The data examined included clinical and pathologic stage, surgical procedure, additional therapy received, and outcome. RESULTS Pathology included Leydig tumors in six patients, Sertoli tumors in four patients, sex cord,stromal tumors in five patients, a granulosa cell tumor in one patient, and a poorly differentiated non,germ cell tumor in one patient. Nine patients had histologic features suggestive of malignancy. Clinical stage at surgery was Stage I in nine patients and Stage IIA,IIIA in eight patients. Patients underwent modified or bilateral RPLND. Nine patients had pathologic Stage I tumors, and the remaining eight patients and had pathologic Stage IIB,IIIA tumors. Follow-up ranged from 8 months to 11 years. Of the eight patients with Stage II,III disease, six patients eventually died of metastatic disease despite additional radiotherapy and/or chemotherapy. CONCLUSIONS Sex cord,stromal tumors have a potentially aggressive malignant behavior that is difficult to predict based on clinical and pathologic features. Although the therapeutic role of RPLND in patients with small-volume metastatic retroperitoneal tumors is unclear, RPLND remains an option to be performed immediately after orchiectomy, especially in patients who have tumors with malignant features and/or small-volume metastatic disease. Cancer 2003;98:753,7. © 2003 American Cancer Society. [source] Testicular carcinoma and HLA Class II genesCANCER, Issue 9 2002Dirk J. A. Sonneveld M.D., Ph.D. Abstract BACKGROUND The association with histocompatibility antigens (HLA), in particular Class II genes (DQB1, DRB1), has recently been suggested to be one of the genetic factors involved in testicular germ cell tumor (TGCT) development. The current study, which uses genotyping of microsatellite markers, was designed to replicate previous associations. METHODS In 151 patients, along with controls comprising parents or spouses, the HLA region (particularly Class II) on chromosome 6p21 was genotyped for a set of 15 closely linked microsatellite markers. RESULTS In both patients and controls, strong linkage disequilibrium was observed in the genotyped region, indicating that similar haplotypes are likely to be identical by descent. However, association analysis and the transmission disequilibrium test did not show significant results. Haplotype sharing statistics, a haplotype method that derives extra information from phase and single marker tests, did not show differences in haplotype sharing between patients and controls. CONCLUSION The current genotyping study did not confirm the previously reported association between HLA Class II genes and TGCT. As the HLA alleles for which associations were reported are also prevalent in the Dutch populations, these associations are likely to be nonexistent or much weaker than previously reported. Cancer 2002;95:1857,63. © 2002 American Cancer Society. DOI 10.1002/cncr.10903 [source] Cardiac metastasis from testicular mixed germ cell tumorCLINICAL CARDIOLOGY, Issue 10 2001Jamshid Alaeddini M.D. No abstract is available for this article. [source] Aspiration biopsy cytomorphology of primary pulmonary germ cell tumor metastatic to the brainDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2009Haitham Arabi M.D. Abstract Extragonadal germ cell tumors are uncommon and such tumors originating from the lung parenchyma are extremely rare. This is a case of 68-year-old female who was admitted with complaints of right-sided weakness, inability to maintain her balance, right-sided headache, and bloody sputum. Her workup revealed two enhancing brain lesions and large lung mass involving the left lower lobe. Fine-needle aspiration (FNA) of the lung followed by craniotomy was performed and the patient was initially diagnosed with lung adenocarcinoma metastatic to the brain based on the cytomorphology of the lung FNA and histology of the brain mass. However, retrospective investigation revealed markedly elevated alpha fetoprotein (AFP) of which the cytopathologist was unaware at the time of diagnosis. A review of the cytology and surgical specimen slides, as well as immunohistochemistry (IHC) on the brain tumor and FNA cell block were preformed. On the basis of the slides review, clinical findings, and immunostaining results, a diagnosis of primary pulmonary mixed germ cell tumor, containing choriocarcinoma and yolk sac elements, with brain metastases, was retrospectively made. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Cerebral hemiatrophy with superficial siderosis and PLEDs due to a germ cell tumor of the basal gangliaEUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2006N. Kumar The diagnosis of basal ganglia germ cell tumors may be delayed due to slow progression and minimal early changes on magnetic resonance imaging (MRI). The cystic nature of some tumors may lead to non-diagnostic biopsies. We describe the clinical, imaging, laboratory, and postmortem findings of a basal ganglia germ cell tumor in a 19-year-old man. Clues to an early antemortem diagnosis based on MRI findings and determination of tumor markers are discussed. An early diagnosis and accurate characterization of basal ganglia germ cell tumors is essential for optimal therapy. The presence of cerebral hemiatrophy and hemorrhagic or cystic components is suggestive. Measurement of serum and cerebrospinal fluid markers such as human chorionic gonadotropin may suggest the diagnosis. [source] Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adultsGENES, CHROMOSOMES AND CANCER, Issue 7 2008Alan McIntyre Testicular germ cell tumors (TGCTs) of adults and adolescents are thought to be derived from primordial germ cells or gonocytes. TGCTs develop postpuberty from precursor lesions known as intratubular germ cell neoplasia undifferentiated. The tumors can be divided into two groups based on their histology and clinical behavior; seminomas resemble primordial germ cells or gonocytes and nonseminomas resemble embryonic or extraembryonic tissues at various stages of differentiation. The most undifferentiated form of nonseminoma, embryonal carcinoma, resembles embryonic stem cells in terms of morphology and expression profiling, both mRNAs and microRNAs. Evidence supports both environmental factors and genetic predisposition underlying the development of TGCTs. Various models of development have been proposed and are discussed. In TGCTs, gain of material from the short arm of chromosome 12 is invariable: genes from this region include the proto-oncogene KRAS, which has activating mutations in ,10% of tumors or is frequently overexpressed. A number of different approaches to increase the understanding of the development and progression of TGCTs have highlighted the involvement of KIT, RAS/RAF/MAPK, STAT, and PI3K/AKT signaling. We review the role of these signaling pathways in this process and the potential influence of environmental factors in the development of TGCTs. © 2008 Wiley-Liss, Inc. [source] Further characterization of the first seminoma cell line TCam-2GENES, CHROMOSOMES AND CANCER, Issue 3 2008Jeroen de Jong Testicular germ cell tumors of adolescents and adults (TGCTs) can be classified into seminomatous and nonseminomatous tumors. Various nonseminomatous cell lines, predominantly embryonal carcinoma, have been established and proven to be valuable for pathobiological and clinical studies. So far, no cell lines have been derived from seminoma which constitutes more than 50% of invasive TGCTs. Such a cell line is essential for experimental investigation of biological characteristics of the cell of origin of TGCTs, i.e., carcinoma in situ of the testis, which shows characteristics of a seminoma cell. Before a cell line can be used as model, it must be verified regarding its origin and characteristics. Therefore, a multidisciplinary approach was undertaken on TCam-2 cells, supposedly the first seminoma cell line. Fluorescence in situ hybridization, array comparative genomic hybridization, and spectral karyotyping demonstrated an aneuploid DNA content, with gain of 12p, characteristic for TGCTs. Genome wide mRNA and microRNA expression profiling supported the seminoma origin, in line with the biallelic expression of imprinted genes IGF2/H19 and associated demethylation of the imprinting control region. Moreover, the presence of specific markers, demonstrated by immunohistochemistry, including (wild type) KIT, stem cell factor, placental alkaline phosphatase, OCT3/4 (also demonstrated by a specific Q-PCR) and NANOG, and the absence of CD30, SSX2-4, and SOX2, confirms that TCam-2 is a seminoma cell line. Although mutations in oncogenes and tumor suppressor genes are rather rare in TGCTs, TCam-2 had a mutated BRAF gene (V600E), which likely explains the fact that these cells could be propagated in vitro. In conclusion, TCam-2 is the first well-characterized seminoma-derived cell line, with an exceptional mutation, rarely found in TGCTs. © 2007 Wiley-Liss, Inc. [source] Imbalances of chromosome arm 1p in pediatric and adult germ cell tumors are caused by true allelic loss: A combined comparative genomic hybridization and microsatellite analysisGENES, CHROMOSOMES AND CANCER, Issue 11 2006Susanne Zahn Previous studies on childhood germ cell tumors (GCTs) report highly variable frequencies of losses at chromosome arm 1p. Since deletions at 1p portend a poor prognosis in other embryonal tumors, this study aims to clarify the question of the frequency of true allelic loss at 1p and whether it constitutes a prognostic parameter. We analyzed 13 GCTs from different gonadal and extragonadal sites of children (4 teratomas, 9 malignant GCTs) and 18 GCTs of adolescents and adults (3 teratomas; 15 malignant GCTs) using automated microsatellite analysis with 23 polymorphic markers and chromosomal "high resolution" comparative genomic hybridization (HR-CGH). With this combined approach, we detected loss of heterozygosity (LOH) at 1p in 8/9 childhood malignant GCTs with concordant data from HR-CGH and microsatellite analyses. In contrast, LOH at 1p was not detected in childhood teratomas (0/4) and constituted a rare event in GCTs of adolescence and adulthood (3/18). The commonly deleted region was located at distal 1p36-pter, with a proximal boundary between the markers D1S450 and D1S2870. These data unequivocally demonstrate that deletion at 1p is common in childhood GCTs and results in allelic loss. This observation argues for the presence of a classical tumor suppressor at distal 1p. Considering the high frequency of LOH at 1p and the overall favorable prognosis of childhood GCTs, a prognostic impact of LOH at 1p in childhood GCTs appears unlikely. However, since two postpubertal tumors with LOH at 1p progressed, a prognostic relevance in this age group seems possible, warranting a prospective evaluation. © 2006 Wiley-Liss, Inc. [source] High-resolution comparative genomic hybridization detects extra chromosome arm 12p material in most cases of carcinoma in situ adjacent to overt germ cell tumors, but not before the invasive tumor developmentGENES, CHROMOSOMES AND CANCER, Issue 2 2003Anne Marie Ottesen High-resolution comparative genomic hybridization (HR-CGH) analysis was performed on DNA purified from laser-capture microdissected carcinoma in situ (CIS) cells from nine cases of CIS, either from tissue without any invasive tumor or from testicular parenchyma adjacent to seminoma, nonseminoma, or a combined germ cell tumor. Before CGH analysis, DNA was amplified by degenerate oligonucleotide primed PCR (DOP-PCR) and directly labeled with a mixture of FITC-dUTP and FITC-dCTP. CGH analysis revealed extra chromosome arm 12p material in six out of seven cases with CIS adjacent to overt tumors, but only a diminutive gain of 12q was noted in one of the two cases of CIS without invasive elements. In addition, gains of parts of chromosome 8 (3/7) and losses of chromosome 5 (2/7) were demonstrated in CIS adjacent to invasive tumors. Gains of parts of chromosome 7 were found in CIS adjacent to seminoma (4/4), whereas relative gains of chromosome 15 were identified in some cases of CIS adjacent to seminoma and in isolated CIS in comparison to CIS adjacent to nonseminoma. Our data seem to indicate that extra 12p material is not present in the "dormant" CIS cell before development of an invasive tumor. The gain of extra chromosome 12 material may not be an early event in the neoplastic transformation, but is most likely associated with a more malignant progression of the CIS cell. © 2003 Wiley-Liss, Inc. [source] Genome profiles of familial/bilateral and sporadic testicular germ cell tumorsGENES, CHROMOSOMES AND CANCER, Issue 2 2002Sigrid Marie Kraggerud In order to investigate the genetics of testicular germ cell tumors (TGCTs), we examined 33 TGCTs, including 15 familial/bilateral and 18 sporadic tumors, using comparative genomic hybridization. The frequencies of the histological subtypes were comparable between the two groups. Gains of the whole or parts of chromosome 12 were found in 30 tumors (91%). Furthermore, increased copy number of the whole or parts of chromosomes 7, 8, 17, and X, and decreased copy number of the whole or parts of chromosomes 4, 11, 13, and 18 were observed in ,50% of the tumors. Sixteen smallest regions of overlapping changes were delineated on 12 different chromosomes. The chromosomal copy numbers of familial/bilateral and sporadic TGCTs were comparable, suggesting similar genetic pathways to disease in both groups. However, significant differences were observed between the two main histological subgroups. Gains from 15q and 22q were associated with seminomas (P = 0.005 and P = 0.02, respectively), whereas gain of the proximal 17q (17q11.2,21) and high-level amplification from chromosome arm 12p, and losses from 10q were associated with nonseminomas (P < 0.001, P = 0.04, and P = 0.03, respectively). © 2002 Wiley-Liss, Inc. [source] Endogenous DNA damage and testicular germ cell tumorsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2009M. B. Cook Summary Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case,case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR50th percentile = 3.31, 95% CI: 1.00, 10.98; OR75th percentile = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR50th percentile = 2.27, 95% CI: 0.75, 6.87; OR75th percentile = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma. [source] HERV-K(HML-2) GAG/ENV antibodies as indicator for therapy effect in patients with germ cell tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2004Anna Kleiman Abstract Germ cell tumors (GCT) are strictly associated with the expression of HERV-K(HML-2) proviruses, and the majority of GCT patients produce antibodies to structural proteins of these proviruses. The objective of our study was to determine the significance of the serological response to HERV-K(HML-2) Gag and Env proteins for diagnosis, management of GCT patients and estimation of the therapy success. The data document a strong association of HERV-K(HML-2) antibodies and the clinical manifestation of the disease and therapy success. HERV-K(HML-2) antibodies seem to have an important diagnostic value as well as indicator of chemotherapy success. © 2004 Wiley-Liss, Inc. [source] Brain metastases from testicular germ cell tumors: A retrospective analysisINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2009Norio Nonomura Objectives: To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them. Methods: Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed. Results: Twenty-six were non-seminomatous tumors and only one was a seminoma. Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in all patients. Additionally, whole-brain radiotherapy was performed in 10 cases, stereotactic radiosurgery in six, whole-brain radiotherapy combined with stereotactic radiosurgery in three and complete surgical resection in five. Three patients received chemotherapy only. Cancer-specific 5- and 10-year survival rates were both 35.9%. The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment. Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases. No other significant prognostic factor was found at multivariate analysis. Conclusion: Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy. [source] Stage I seminoma: What should a practicing uro-oncologist do in 2009?INTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2009Julia Skliarenko Abstract Testicular tumors are uncommon, but they continue to represent an important group of malignancies in young men. It is the most common solid malignancy in males between the ages of 20 and 35, and primary germ cell tumors are the most common histological type. In the United States in 2008, approximately 4800 cases of seminoma, approximately 4100 of which were stage I disease were projected after the completion of staging investigations. Remarkable progress has been made in the treatment of testicular seminoma over the past 25 years. Management options of stage I seminoma include radiotherapy, surveillance, or adjuvant chemotherapy. Standard management until recent years has been adjuvant retroperitoneal radiotherapy. Although providing excellent long term results, this approach has been associated with increased risk of gonadal toxicity, development of secondary malignancies and an increased risk of cardiovascular disease. The use of surveillance in management of patients with stage I seminoma is therefore becoming more frequent as it minimizes the burden of treatment and maintains the cure rate at virtually 100%. Adjuvant chemotherapy using Carboplatin has been investigated as an alternative management approach. However, the long term outcomes of patients managed with Carboplatin are not yet clear and this strategy should only be used in a study setting. It has been suggested that more patients with stage I seminoma will die of their treatment than of their cancer; therefore, the thrust of modern management should be to maintain 100% cure while minimizing the burden of treatment. [source] | |||||||||||||||||||||||||