Cancer Report

Cancer : Testis: Germ cell tumors
Summary
Cancer Name Testis: Germ cell tumors
Cancer Alias Testicular cancer
Description Germ cell tumours comprise a heterogeneous group of neoplasms, which can be found at different, although restricted anatomical locations. In the testis three groups of germ cell-derived tumours are distinguished:
  • I- teratomas and yolk sac tumours of infants;
  • II- seminomas and nonseminomas of adolescents and adults;
  • III- spermatocytic seminomas of the elderly.
These groups are defined by epidemiological characteristics, histological composition and chromosomal constitution (Table 1). Designation of tumours to these groups is clinically relevant because they require different strategies for treatment
 
Clinics and Pathology
Disease Testicular germ cell tumours, teratomas and yolk sac tumours, seminomas and nonseminomas, carcinoma in situ (CIS), intratubular germ cell neoplasia undifferentiated (IGCNU) , testicular intratubular neoplasia (TIN) , spermatocytic seminomas
Epidemiology During the first few years of life, the only types of germ cell tumours diagnosed in the testis are teratomas and yolk sac tumours. They are evidently unrelated to puberty. In contrast, the seminomas, nonseminomas, and spermatocytic seminomas are clinically manifest during or after puberty, therefore likely related to sexual maturation. Spermatocytic seminomas are predominantly found in patients of 50 years and older. While most patients with a seminoma present in their 4th decade of life, this is in the 3rd decade for patients with a nonseminoma. An increasing incidence (in between 6-11/100.000) has been reported both for seminomas and nonseminomas during the last decades in white populations throughout the world, with an annual increase of 3-6%. Although in general rare, accounting for 1-2% of all malignancies in males, seminomas and nonseminomas are the most common cancer in young Caucasian males. In some European countries, i.e., Denmark and Switzerland, the life time risk for seminoma or nonseminoma is up to 1%. However, the increase seems to stabilise to date. In contrast to whites, blacks have a significantly lower, not increasing, incidence for seminomas/nonseminomas, although histology and age-distribution are the same. No significantly increasing incidence has been reported for teratomas and yolk sac tumours of infants and spermatocytic seminomas.
The incidence of CIS, the precursor of both seminomas and nonseminomas, in the general population is similar to the life time risk to develop a seminoma/nonseminoma. This indicates that CIS will always progress to invasiveness. About 5% of patients with a unilateral seminoma or nonseminoma have contralateral CIS.
Pathology CIS cells show similarities to embryonic germ cells, like their positivity for alkaline phosphatase, the stem cell factor receptor (c-KIT), and their glycogen content. These cells are frequently found in the adjacent parenchyma of an invasive seminoma and nonseminoma, of which a representative example is given in Figure 1. Histologically and immunohistochemically, seminoma cells mimick CIS. Lymphocytic infiltrations in the supportive stroma are a consistent feature of these tumors (Figure 2). So far, no differences have been found between CIS and seminoma cell, except the invasive growth of the latter. In contrast to the homogeneity of CIS and seminomas, nonseminomas can be composed of different elements, including embryonal carcinoma (the undifferentiated, stem cell, component), teratoma (the somatically differentiated component), yolk sac tumour and choriocarcinoma (the components of extra-embryonal differentiation) (see Figure 3-6). These different histological elements can be identified using immunohistochemistry for different markers, like CD30 for embryonal carcinoma, alpha fetoprotein (AFP) for yolk sac tumour, and human chorionic gonadotropin (hCG) for choriocarcinoma (see illustrations). Most nonseminomas are mixtures of these different elements. About 50% of germ cell tumors of adolescents and adults are pure seminomas, and 40% pure or mixed nonseminomas. Tumours containing both a seminoma and a nonseminoma component are classified as combined tumours according to the British Classification system, and as nonseminomas according to the World Health Organisation (WHO) classification. These tumours present at an age in between that of pure seminoma and nonseminoma.
The spermatocytic seminomas are histologically uniform and composed of three cell types, small, intermediate and large cells, that are evenly distributed (Figure 7). The immunohistochemical markers for CIS/seminoma are overall negative in spermatocytic seminomas. So far, no specific markers have been reported for spermatocytic seminomas, Histologically and immunohistochemically, the teratoma and yolk sac tumour components found in the infantile testis are indistinguishable from those elements found in nonseminomas of the adult testis. However, they differ in chromosomal constitution (see Table 1 and below), and the first lack CIS in the adjacent parenchyma.
Prognosis The teratomas of infants, and the spermatocytic seminomas are generally benign. Therefore, orchidectomy alone is mostly curative. However, spermatocytic seminomas may progress to sarcoma, a highly malignant tumour. When the yolk sac tumour component of infants is metastatic, it can be cured in the majority of patients using chemotherapy. Seminomas are highly sensitive to irradiation, while nonseminomas are overall highly sensitive to cisplatin-based chemotherapy, with cure rates of up to 90%. Criteria have been developed to distinguish nonseminoma patients with a good, intermediate and poor response (Table 2). Although these parameters are not informative on an individual basis, they separate the three groups as a whole. Seminoma patients always fall in the good and intermediate prognostic group.
Stage I disease might be treated by orchidectomy followed by a "wait and see" strategy. Alternatively, retroperitoneal lymph node dissection (nerve sparing) and/or irradiation (in case of pure seminoma) can be performed. Moreover, a single dose cisplatin-based chemotherapy is tested in an experimental set up. These issues are of interest, because the risk of occult metastases in clinically stage I nonseminomas is about 30%. Established factors predicting metastastic disease are lymphovascular space invasion and percentage of embryonal carcinoma. For nonseminomas there is no consensus on the best method to define the risk of occult metastases and on how the information can be used for the clinical management of patients. In clinically stage I seminoma patients occult metastases are predicted by vascular invasion and tumor size. More recently, the mean nuclear volume has been reported to be an informative parameter. Obviously these parameters could serve to define a group of patients that could benefit from surveillance. Patients with refractory disease might benefit from high-dose chemotherapy.
Because CIS is formed during intra-uterine growth, and the treatable cancer in most cases becomes clinically manifest after puberty, methods for early diagnosis and treatment might prevent progression of CIS to an invasive seminoma or nonseminoma, thereby preventing possible progression to refractory disease. A number of putative parameters have been reported, although none of them have been tested in a clinical setting thus far. Moreover, it has been shown that CIS can be effectively eradicated using local irradiation, with limited side effects.
The presence of CIS in the contralateral testis in 5% of patients with a seminoma or nonseminomas has led to the routine of a contralateral biopsy in some countries. However, in most countries the clinicians prefer a closely "wait and see" strategy. Patients with cryptorchidism, atrophic testis, or prior infertility have a higher risk of CIS in the contralateral testis. The exact numbers are unknown, but it is estimated that high-risk patients comprise 40-50% of the population with CIS. Altogether about 50-60% of patients with a unilateral testis tumor will have no other risk factors for CIS.
 
Related Genes
Gene Symbol TOPORS
Description From COSMIC:
 
Gene Symbol STK11
Description From COSMIC:
 
Gene Symbol CASP9
 
Gene Symbol STK10
Description From COSMIC:
 
Gene Symbol CDKN2A
Description From COSMIC:
 
Gene Symbol SNF1LK
Description From COSMIC:
 
Gene Symbol APAF1
Description "Tumors of the male reproductive organs ( seminoma, nonseminomatous http://atlasgeneticsoncology.org/Tumors/malegermID5005.html, germ cell tumors , http://atlasgeneticsoncology.org/Tumors/OvarSexCordStromID5223.html, sex cord-stromal tumors , other testis cancers, neoplasms of prostate, tumor of the penis)"
 
Gene Symbol K-RAS
Description From COSMIC:
 
Gene Symbol N-RAS
Description From COSMIC:
 
Gene Symbol FAS
Description From cancer gene census of CGP:
 
Gene Symbol KIT
Description From COSMIC, cancer gene census of CGP
 
Gene Symbol PTENP1
Description From COSMIC:
 
Gene Symbol MADH4
Description From COSMIC:
 
Gene Symbol ERBB2
 
Gene Symbol MET
Description From COSMIC:
 
Gene Symbol LATS2
Description :
 
Cytogenetics
Cytogenetics Morphological
  • The three groups of germ cell tumours of the testis show characteristic chromosomal anomalies, which favor the model of separate pathogeneses. The chromosomal data on germ cell tumors of the infantile testis and spermatocytic seminomas are scarse.
  • While no aberrations are found so far in teratomas of the infantile testis, the yolk sac tumours show recurrent loss of part of 6q, and gain of parts of 1q, 20q, and 22. In addition, these yolk sac tumours are all found to be aneuploid.
  • One study reports the analysis of spermatocytic seminomas by karyotyping and comparative genomic hybridization, showing gain of chromosome 9 as the only recurrent and characteristic chromosomal abnormality.
  • Seminomas, nonseminomas as well as CIS are consistently aneuploid with a characteristic pattern of chromosomal gains and losses. The cells of seminoma and CIS are hypertriploid, while those of nonseminoma, irrespective of histological composition, are hypotriploid. Using karyotyping, more recently supported by in situ and comparative genomic hybridization, a complex, but similar pattern of over- and underrepresentation of (parts of) chromosomes has been identified in seminomas and nonseminomas. Overall, the chromosomes 4, 5, 11, 13, 18 and Y are underrepresented, while the chromosomes 7, 8, 12 and X are overrepresented. In spite of the highly similar pattern of gains and losses in seminomas and nonseminomas, some differences were observed, like overrepresentation of chromosome 15 in seminomas compared to nonseminomas, which might explain the ploidy difference between these two histological groups.
  • The recurrent pattern of chromosomal gains and losses suggests that both activation of proto-oncogenes, and inactivation of tumor suppressor genes is involved in the development of this cancer.
  • Gain of 12p The isochromosome 12p can be used as a diagnostic molecular marker for seminomas and nonseminomas: the most consistent chromosomal anomaly in seminomas and nonseminomas, besides their aneuploidy, is gain of the short arm of chromosome 12. In fact, about 80% of the invasive tumors have extra copies of 12p due to the formation of an isochromosome (i(12p)) (Figure). The 20% i((12p) negative tumors also show gain of 12p, due to other chromosomal changes. These data strongly indicate that the short arm of chromosome 12 contains a gene or genes of which extra copies are required for the development of the invasive tumor. Analysis of LOH on the long arm of chromosome 12 showed that polyploidisation occurs prior to i(12p) formation. In addition, it was demonstrated that i(12p) results from sister chromatin exchange. In contrast, non-sister cromatin exchange has also been suggested. Most recently, it was shown that the presence of extra copies of the short arm of chromosome 12 is related to invasive growth of the tumor, i.e., no gain of 12p is observed in CIS. This suggests that addition copies of one or more genes on 12p is relevant for the progression of CIS to an invasive tumor. Analysis of seminomas and nonseminomas containing a high level amplification of a restricted region of 12p, i.e., band p11.2-12.1, cyclin D2 being outside this region, might be a tool to identify the gene(s) on 12p. So far, these data suggest that is relates to a gene that suppresses induction of apoptosis upon invasive growth of the tumour cells.
  • Proto-oncogenes Several studies deal with the possible role of activation of proto-oncogenes in the development of seminomas and nonseminomas. RAS genes are rarely found to be mutated One study reported the presence of mutations in c-KIT in some cases. Overexpression of c-MYC has been found in less than 10% of nonseminomas, and amplification of MDM2 in also less than 10% of the tumors. Cyclin D2 has been suggested as the candidate gene on 12p. However, this gene maps outside the amplified region found in some seminomas and nonseminomas. In conclusion, the role of activation of proto-oncogenes in the genesis of seminomas and nonseminomas is not illucidated so far.
  • Tumor suppressor genes Studies of loss of heterozygosity (LOH), a hallmark of the involvement of tumor suppressor genes, have given rather inconsistent results in seminomas and nonseminomas, which might be related to their aneuploidy. Several studies have been performed on chromosomes 1, 5, 11, 12 and 18. Recurrent loss has been observed on 1p, in particular bands p13, p22, p31.3-p32, and 1q; in particular bands q32. Several regions on chromosome 5 show LOH, including p15.1-p15.2, q11, q14, q21, and q34-qter. Chromosome 12 contains two regions of interest, i.e., q13 and q22. In spite of the identification of homozygous deletions at 12q22, no candidate genes have been identified so far. Homozygous deletions have also been identified on the long arm of chromosome 18. Although DCC (deleted in colorectal cancer) might be a candidate, it has been indicated that loss of this gene is likely progression-related. More recently, inactivating mutations of SMAD4, also mapped to 18q, have been reported in a limited number of seminomas. LOH analysis on microdissected tumor cells of different histologies, including CIS, revealed recurrent LOH at 3q27-q28, 5q31, 5q34-q35, 9p21-p22 and 12q22. These anomalies were also found in the adjacent CIS cells. Interestingly, loss of 3q27-q28 was only but consistently detected in the embryonal carcinoma components. The other targets investigated with overall negative findings are: NME1 and 2, APC, MCC, RB, WT1, and P53. However, hypermethylation of exon 1 of p16 was found in about 50% of the tumors, which was related to no, or a low level of expression.
  • In summary, although interesting observations have been made, no convincing data based on studies on LOH, mutations and expression so far, indicate a significant involvement of one of the studied tumor suppressor genes in the development of testicular seminomas and nonseminomas. Moreover, no candidate genes have been identified for the teratomas and yolk sac tumors of the infantile testis, as well as for spermatocytic seminomas.
  • Cytogenetics Molecular The isochromosome 12p can be identified on interphase nuclei by fluorescent in situ hybridization, using simultaneously a probe specific for the centromeric region and the short am of chromosome 12. The use of the centromeric probe only was not found to be informative.
     
    Bibliography
    Title herlapati R, Wang X, Chaganti RS , Murty VV.
    Authors Bala S, Oliver H, Renault B, Montgomery K, Dutta S, Rao P, Houldsworth J, Kuc
    Citations Cancer Res 1995; 55: 2871-2875.
    PubMedID 10655070
     
    Title X inactivation in human testicular tumors. XIST expression and androgen receptor methylation status.
    Authors Looijenga LHJ, Gillis AJM, Van Gurp RJHLM, Verkerk AJMH , Oosterhuis JW.
    Citations Am J Pathol 1997; 151: 581-590.
    PubMedID 10655070
     
    Title Possible carcinoma-in-situ of the testis.
    Authors Skakkebæk NE.
    Citations Lancet 1972; 516-517.
    PubMedID 8293405
     
    Title Prevalence of carcinoma-in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly.
    Authors Giwercman A, Müller J , Skakkebæk NE.
    Citations J Urol 1991; 145: 77-80.
    PubMedID 10952776
     
    Title Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms.
    Authors Dieckmann KP , Loy V.
    Citations J Clin Oncol 1996; 14: 3126-3132.
    PubMedID 10861580
     
    Title Prognosis of primary testicular seminoma: a report on 57 new cases.
    Authors Fujikawa K, Matsui Y, Oka H, Fukuzawa S, Sasaki M , Takeuchi H.
    Citations Int J Cancer 1999; 83: 848-51.
    PubMedID 10616195
     
    Title Restricted 12p-amplification and RAS mutation in human germ cell tumors of the adult testis.
    Authors Roelofs H, Mostert MC, Pompe K, Zafarana G, Van Oorschot M, Van Gurp RJHLM, Gillis AJM, Stoop H, Rodenhuis S, Oosterhuis JW, Bokemeyer C , Looijenga LJ.
    Citations Genes Chromosomes Cancer 1994; 9: 153-160.
    PubMedID 1683567
     
    Title Restricted 12p-amplification and RAS mutation in human germ cell tumors of the adult testis.
    Authors Roelofs H, Mostert MC, pompe K, Zafarana G, Van Oosrschot M, Van Gurp RHJLM, Gillis AJM, Stoop H, Beverloo B, J.W. o, Bokemeyer C , Looijenga LHJ.
    Citations Genes Chromosom Cancer 1994; 11: 126-135.
    PubMedID 1683567
     
    Title Reviews of chromosome studies in urological tumors. 3. Cytogenetics and genes in testicular tumors.
    Authors Sandberg AA, Meloni AM , Suijkerbuijk RF.
    Citations J Urol 1996; 155: 1531-1556.
    PubMedID 9053482
     
    Title Spermatocytic seminoma. A clinicopathologic study of 79 cases.
    Authors Burke AP , Mostofi FK.
    Citations J Urol Path 1993; 1: 21-32.
    PubMedID 8647654
     
    Title Testicular cancer in blacks.
    Authors Moul JW, Schanne FJ, Thompson IM, Frazier HA, Peretsman SA, Wettlaufer JN, Rozanski TA, Stack RS, Kreder KJ , Hoffman KJ.
    Citations A multicenter experience. Cancer 1994; 73: 388-393.
    PubMedID 8382754
     
    Title Testicular germ cell tumors of adults show deletions of chromosomal bands 11p13 and 11p15.5, but no abnormalities within the zinc-finger regions and exons 2 and 6 of the Wilms' tumor 1 gene.
    Authors Looijenga LHJ, Abraham M, Gillis AJM, Saunders GF , Oosterhuis JW.
    Citations Genes Chromosom Cancer 1993; 7: 96-101.
    PubMedID 11127816
     
    Title The biology of human germ cell tumours: Retrospective speculations and new prospectives.
    Authors Oosterhuis JW , Looijenga LHJ.
    Citations Eur Urol 1993; 23: 245-250.
    PubMedID 8390358
     
    Title The cytogenetic theory of the pathogenesis of human adult male germ cell tumours.
    Authors Chaganti RSK , Houldsworth J.
    Citations APMIS 1998; 106: 80-84.
    PubMedID 9140458
     
    Title The p53 and mdm-2 genes in human testicular germ-cell tumors.
    Authors Riou G, Barrois M, Prost S, Terrier MJ, Theodore C , Levine AJ.
    Citations Cell Growth Developm 1997; 8: 293-299.
    PubMedID 8527395
     
    Title Treatment of patients with cisplatin-refractory testicular germ-cell cancer. German Testicular Cancer Study Group (GTCSG).
    Authors Bokemeyer C, Kollmannsberger C, Harstrick A, Beyer J, Gerl A, Casper J, Metzner B, Hartmann JT, Schmoll HJ , Kanz L.
    Citations Int J Androl 1996; 19: 365-70.
    PubMedID 1381946
     
    Title Treatment of testicular cancer and the development of secondary malignancies.
    Authors Bokemeyer C , Schmoll HJ.
    Citations J Clin Oncol 1995; 13: 283-292.
    PubMedID 8627820
     
    Title Uniparental origin of i(12p) in human germ cell tumors.
    Authors Sinke RJ, Suijkerbuijk RF, De Jong B, Oosterhuis JW , Geurts van Kessel A.
    Citations Genes Chromosom Cancer 1991; 3: 300-307.
    PubMedID 8627820
     
    Title microRNAs as oncogenes and tumor suppressors.
    Authors "Zhang B, Pan X, Cobb GP, Anderson TA."
    Citations Dev Biol. 2007 Feb 1;302(1):1-12.
    PubMedID 16989803
     
    Title Combined tumours.
    Authors Pugh RCB
    Citations In: Pugh, R. C. B., eds. Book. Oxford: Blackwell, (1976): 245-258.
    PubMedID 9051423
     
    Title Clonality of combined testicular germ cell tumors of adults. Lab Invest 1994; 71: 874-878.
    Authors Gillis AJM, Looijenga LHJ, De Jong B , Oosterhuis JW.
    Citations Brit J Cancer 2000; 83: 729-736.
    PubMedID 8913724
     
    Title Comparative genomic hybridization of germ cell tumors of the adult testis; confirmation of karyotypic findings and identification of a 12p-amplicon.
    Authors Mostert MC, Van de Pol M, Olde Weghuis D, Suijkerbuijk RF, Geurts van Kessel A, Van Echten-Arends J, Oosterhuis JW , Looijenga LHJ.
    Citations Genes Chromosom Cancer 1997; 20: 412-418.
    PubMedID 8700532
     
    Title Comparative genomic and in situ hybridization of germ cell tumors of the infantile testis.
    Authors Mostert MC, Rosenberg C, Stoop H, Schuyer M, Timmer A, Oosterhuis JW , Looijenga LHJ.
    Citations Lab Invest 2000; 80: 1055-1064.
    PubMedID 2536126
     
    Title Chromosomal deletions occur in restricted regions of 5q in testicular germ cell cancer.
    Authors Peng HQ, Liu L, Goss PE, Bailey D , Hogg D.
    Citations Genetic analysis of the APAF1 gene in male germ cell tumors. Genes Chromosom Cancer 2000; 28: 258-68.
    PubMedID 9524565
     
    Title Chromosomal constitution of human spermatocytic seminomas: comparative genomic hybridization suppored by conventional and interphase cytogenetics.
    Authors Rosenberg C, Mostert MC, Bakker Schut T, Van de Pol M, Van Echten-Arends J, De Jong B, Raap T, Tanke H, Oosterhuis JW , Looijenga LHJ.
    Citations Genes Chromosom & Cancer 1998; 23: 286-291.
    PubMedID 9524565
     
    Title Chromosome 12q heterozygosity is retained in i(12p)-positive testicular germ cell tumor cells.
    Authors Geurts van Kessel A, Van Drunen E, De Jong B, Oosterhuis JW, Langeveld A , Mulder MP.
    Citations Genes Chromosom Cancer 1993; 6: 161-165.
    PubMedID 10862031
     
    Title Chromosomal gains and losses in testicular germ cell tumors of adolescents and adults investigated by a modified CGH approach.
    Authors Rosenberg C, Bakker Schut T, Mostert MC, Tanke HJ, Raap AK, Oosterhuis JW , Looijenga LHJ.
    Citations Genes Chromosom Cancer 1992; 5: 109-118.
    PubMedID 10862031
     
    Title Detection and enrichment of carcinoma-in-situ cells in semen by an immunomagnetic method using monoclonal antibody M2A.
    Authors Meng FJ, Zhou Y, Skakkebaek NE, Marks A , Giwercman A.
    Citations Proc Natl Acad Sci USA 1996; 93: 2884-2888.
    PubMedID 7535083
     
    Title Detection and analysis of origin of i(12p), a diagnostic marker of human male germ cell tumors by fluorescent in situ hybridization.
    Authors Mukherjee AB, Murty VVVS, Rodriquez E, Reuter VE, Bosl GJ , Chaganti RSK.
    Citations Oncogene 2000; 19: 5858-5862.
    PubMedID 8955658
     
    Title Detection of chromosomal aberrations in seminomatous germ cell tumours using comparative genomic hybridization.
    Authors Ottesen AM, Kirchhoff M, Rajpert De-Meyts E, Maahr J, Gerdes T, Rose H, Lundsteen C, Meidahl Petersen P, Philip J , Skakkebæk NE.
    Citations Brit J Cancer 1998; 77: 305-313.
    PubMedID 8812492
     
    Title Detection of chromosomal DNA gains and losses in testicular germ cell tumors by comparative genomic hybridization.
    Authors Korn MW, Olde Weghuis DEM, Suijkerbuijk RF, Schmidt U, Otto T, Du Manoir S, Geurts van Kessel A, Seeber S , Becher R.
    Citations Cancer Genet Cytogenet 1996; 89: 146-152.
    PubMedID 7936646
     
    Title DNA ploidy in testicular germ cell neoplasms: Histogenetic and clinical implications.
    Authors El-Naggar AK, Ro JY, McLemore D, Ayala AG , Batsakis JG.
    Citations Genes Chromosom & Cancer 1996; 17: 78-87.
    PubMedID 7518576
     
    Title Comparative genomic hybridization of microdissected samples from different stages in the development of a seminoma and a non-seminoma.
    Authors Looijenga LH, Rosenberg C, van Gurp RJ, Geelen E, van Echten-Arends J, de Jong B, Mostert M , Wolter Oosterhuis J.
    Citations Semin Oncol 1998; 25: 160-173.
    PubMedID 9408759
     
    Title Deletion mapping identifies loss of heterozygosity at 5p15.1- 15.2, 5q11 and 5q34-35 in human male germ cell tumors.
    Authors Murty VVVS, Reuter VE, Bosl GJ , Chaganti RSK.
    Citations Genomics 1996; 35: 562-570.
    PubMedID 8955658
     
    Title Decreased testicular cancer risk in men born in wartime.
    Authors Møller H.
    Citations J Natl Cancer Inst 1989; 81: 1668-9.
    PubMedID 8955658
     
    Title Aberrant expression of cyclin D2 is an early event in human male germ cell tumorigenesis.
    Authors Houldsworth J, Reuter V, Bosl GJ , Chaganti RSK.
    Citations Oncogene 1998; 16: 2617-2627.
    PubMedID 2569358
     
    Title Aberrant platelet-derived growth factor a-receptor transcript as a diagnostic marker for early human germ cell tumors of the adult testis.
    Authors Mosselman S, Looijenga LHJ, Gillis AJM, Van Rooijen MA, Kraft HJ, Van Zoelen EJJ , Oosterhuis JW.
    Citations J Pathol 1998; 186: 235-9.
    PubMedID 10362788
     
    Title Activating c-kit gene mutations in human germ cell tumors.
    Authors Tian Q, Frierson HF, Jr., Krystal GW , Moskaluk CA.
    Citations Molec Carcinogen 1995; 12: 124-131.
    PubMedID 9284835
     
    Title Allelic loss and somatic differentiation in human male germ cell tumors.
    Authors Murty VVVS, Bosl GJ, Houldsworth J, Meyers M, Mukherjee AB, Reuter V , Chaganti RSK.
    Citations Oncogene 1994; 9: 3227-3231.
    PubMedID 7529549
     
    Title A comparative analysis of cell surface antigens expressed by cell lines derived from human germ cell tumors.
    Authors Andrews PW, Casper J, Damjanov I, Duggan-Keen M, Giwercman A, Hata J-i, Von Keitz A, Looijenga LHJ, Oosterhuis JW, Pera M, Sawada M, Schmoll H-J, Skakkebæk NE, Van Putten W , Stern P.
    Citations Int J Cancer 1996; 66: 806-816.
    PubMedID 8610136
     
    Title A novel SMAD4 gene mutation in seminoma germ cell tumors.
    Authors Bouras M, Tabone E, Bertholon J, Sommer P, Bouvier R, Droz JP , Benahmed M.
    Citations Am J Pathol 1997; 151: 859-865.
    PubMedID 8610136
     
    Title Candidate regions for testicular cancer susceptibility genes.
    Authors Bishop DT.
    Citations Nat Genet 2000; 24: 197-200.
    PubMedID 9632138
     
    Title Carcinoma in situ of the testis.
    Authors Rørth M, Rajpert-de Meyts E, Skakkebaek NE , et al.
    Citations Scan J Urol 2000; 205: 166-186.
    PubMedID 10521799
     
    Title Carcinoma in situ of the testis: Biology, screening and management.
    Authors Giwercman A , Skakkebæk NE.
    Citations Eur Urol 1993; 23: 19-21.
    PubMedID 7799032
     
    Title Chromosomal constitution and developmental potential of human germ cell tumors and teratomas.
    Authors Oosterhuis JW, Looijenga LH, van Echten J , de Jong B.
    Citations Cancer Genet Cytogenet 1997; 95: 96-102.
    PubMedID 10400552
     
    Title Allellic loss in carcinoma in situ and testicular germ cell tumours of adolescents and adults: evidence in support of the linear progression model.
    Authors Faulkner SW, Leigh DA, Oosterhuis JW, Roelofs H, Looijenga LHJ , Friedlander ML.
    Citations J Pathol 2000; 191: 187-92.
    PubMedID 8697422
     
    Title Analysis of the DCC tumor suppressor gene in testicular germ cell tumors: mutations and loss of expression.
    Authors Strohmeyer D, Langenhof S, Ackermann R, Hartmann M, Strohmeyer T , Schmidt B.
    Citations Cancer Res 2000; 60: 922-8.
    PubMedID 8697422
     
    Title Apoptosis of human seminoma cells upon disruption of their micro-environment.
    Authors Olie RA, Boersman AWM, Dekker MC, Nooter K, Looijenga LHJ , Oosterhuis JW.
    Citations Brit J Cancer 1996; 73: 1031-1036.
    PubMedID 8541838
     
    Title Candidate regions for a testicular cancer susceptibility gene.
    Authors Leahy MG, Tonks S, Moses JH, Brett AR, Huddart R, Forman D, Oliver RTD, Bishop DT , Bodmer JG.
    Citations APMIS 1998; 106: 64-72.
    PubMedID 9056671
     
    Title N- and KRAS mutations in human testicular germ cell tumors: incidence and possible biological implications.
    Authors Olie RA, Looijenga LHJ, Boerrigter L, Top B, Rodenhuis S, Mulder MP , Oosterhuis JW.
    Citations Am J Pathol 1999; 154: 1643-7.
    PubMedID 10706106
     
    Title Molecular cytogenetic analysis of adult testicular germ cell tumours and identification of regions of consensus copy number change.
    Authors Summersgill B, Goker H, Wber-Hall S, Huddart R, Horwich A , Shipley J.
    Citations Lab Invest 1999; 79: 1447-1451.
    PubMedID 10359533
     
    Title Loss of heterozygosity of tumor suppressor genes in testis cancer.
    Authors Peng H-Q, Bailey D, Bronson D, Goss PE , Hogg D.
    Citations J Urol 1997; 157: 1973-1976.
    PubMedID 11021820
     
    Title Loss of heterozygosity identifies multiple sites of allelic deletions on chromosome 1 in human male germ cell tumors.
    Authors Mathew S, Murty VVVS, Bosl GJ , Chaganti RSK.
    Citations Oncogene 1994; 9: 2245-2251.
    PubMedID 11021820
     
    Title Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.
    Authors Rapley EA, Crockford GP, Teare D, et al.
    Citations J Pediatr Hematol Oncol 2000; 22: 100-5.
    PubMedID 11021820
     
    Title K-ras oncogene codon 12 point mutations in testicular cancer.
    Authors Ridanpää M, Lothe RA, Önfelt A, Foss?SD, Børresen AL , Husgafvel-Pursiainen K.
    Citations Genes Chromosom & Cancer 1995; 12: 110-116.
    PubMedID 9112574
     
    Title International Germ Cell Consensus Classification: a prognostic factor- based staging system for metastatic germ cell cancers.
    Authors International Germ Cell Cancer Collaborative Group.
    Citations J Clin Oncol 1997; 15: 594-603.
    PubMedID 9824200
     
    Title Incidence of testicular germ-cell malignancies in England and Wales: trends in children compared with adults.
    Authors Dos Santos Silva I, Swerdlow AJ, Stiller CA , Reid A.
    Citations Int J Cancer 1999; 83: 630-4.
    PubMedID 10547581
     
    Title Ploidy of testicular carcinoma in situ.
    Authors De Graaff WE, Oosterhuis JW, De Jong B, Dam A, Van Putten WLJ, Castedo SMMJ, Sleijfer DT , Schraffordt Koops H.
    Citations Am J Surg Pathol 1992; 16: 611-618.
    PubMedID 7954476
     
    Title Ploidy of primary germ cell tumors of the testis. Pathogenetic and clinical relevance.
    Authors Oosterhuis JW, Castedo SMMJ, De Jong B, Cornelisse CJ, Dam A, Sleijfer DT , Schraffordt Koops H.
    Citations Lab Invest 1989; 60: 14-20.
    PubMedID 8624259
     
    Title Physical mapping of a commonly deleted region, the site of a candidate tumor suppressor gene, at 12q22 in human male germ cell tumors.
    Authors Murty VVVS, Renault B, Falk CT, Bosl GJ, Kucherlapati R , Chaganti RSK.
    Citations Oncogene 1999; 18: 3277-83.
    PubMedID 7687459
     
    Title Pathogenetic and clinical relevance.
    Authors Oosterhuis JW, Castedo SMMJ, De Jong B, Cornelisse CJ, Dam A, Sleijfer DT , Schraffordt Koops H. Ploidy of primary germ cell tumors of the testis.
    Citations Lab Invest 1992; 66: 166-168.
    PubMedID 7687459
     
    Title Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas.
    Authors Rosenberg C, Van Gurp RJHLM, Geelen E, Oosterhuis JW , Looijenga LHJ.
    Citations Oncogene 1998; 16: 2617-27.
    PubMedID 10908150
     
    Title Origin and Biology of a Testicular Wilms' Tumor.
    Authors Gillis AJM, Oosterhuis JW, Schipper MEI, Barten EJ, Van Berlo R, Van Gurp RJHLM, Abraham M, Saunders GF , Looijenga LHJ.
    Citations Cancer Genet Cytogenet 1996; 87: 95-102.
    PubMedID 10908150
     
    Title No recurrent structural abnormalities in germ cell tumors of the adult testis apart from i(12p).
    Authors Van Echten-Arends J, Oosterhuis JW, Looijenga LHJ, Wiersma J, Te Meerman G, Schraffordt Koops H, Sleijfer DT , De Jong B.
    Citations Cancer Genet Cytogenet 1989; 40: 129-134.
    PubMedID 10908150
     
    Title New research in testicular cancer epidemiology
    Authors Swerdlow AJ
    Citations . In: Jones, W. G., Appleyard, I., Harnden, P. & Joffe, J. K., eds. Book. London: John Libbey, (1998): 3-8.
    PubMedID 10908150
     
    Title Frequent allelic deletions and loss of expression characterize the DCC gene in male germ cell tumors.
    Authors Murty VVVS, Li RG, Houldsworth J, Bronson DL, Reuter VE, Bosl GJ , Chaganti RSK.
    Citations Oncogene 1996; 12: 2719-2723.
    PubMedID 8625271
     
    Title Frequent loss of 11p13 and 11p15 loci in male germ cell tumours.
    Authors Lothe RA, Hastie N, Heimdal K, Fossa SD, Stenwig AE , Børresen AL.
    Citations Cancer Res 1994; 54: 6265-6269.
    PubMedID 9632138
     
    Title Fluorescence in situ hybridization analysis of chromosome 12 anomalies in semen cells from patients with carcinoma in situ of the testis.
    Authors Meng FJ, Zhou Y, Giwercman A, Skakkebæk NE, Geurts van Kessel AD , Suijkerbuijk RF.
    Citations Hum Mol Genet 1995; 4: 1551-1555.
    PubMedID 7893365
     
    Title Fluorescence in situ hybridization-based approaches for the detection of 12p-overrepresentation, in particular i(12p), in cell lines of human testicular germ cell tumors of adults.
    Authors Mostert MC, Van de Pol M, Van Echten-Arends J, Olde Weghuis D, Geurts van Kessel A, Oosterhuis JW , Looijenga LHJ.
    PubMedID 7893365
     
    Title Expression of immunohistochemical markers for testicular carcinoma in situ by normal fetal germ cells.
    Authors Jørgensen N, Rajpert-De Meyts E, Graem N, Müller J, Giwercman A , Skakkebæk NE.
    Citations Lab Invest 1995; 72: 223-231.
    PubMedID 1984105
     
    Title Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours.
    Authors Rajpert-De Meyts E , Skakkebæk NE.
    Citations Int J Androl 1994; 17: 85-92.
    PubMedID 10597209
     
    Title Detection of ras mutations in archival testicular germ cell tumors by polymerase chain reaction and oligonucleotide hybridization.
    Authors Moul JW, Theune SM , Chang EH.
    Citations Environ Health Perspect 1993; 101: 185-187.
    PubMedID 7796415
     
    Title Early stage and advanced seminoma: role of radiation therapy, surgery , and chemotherapy.
    Authors Gospodarowicz MK, Sturgeon JFG , Jewett MAS.
    Citations Cancer Res 2000; 60: 2152-4.
    PubMedID 9461002
     
    Title In situ numeric analysis of centromeric regions of chromosomes 1, 12, and 15 of seminomas, nonseminomatous germ cell tumors, and carcinoma in situ of human testis.
    Authors Looijenga LHJ, Gillis AJM, Van Putten WLJ , Oosterhuis JW.
    Citations Lab Invest 1993; 68: 211-219.
    PubMedID 10779021
     
    Title Incidence of testicular cancer in the United States: has the epidemic begun to abate?
    Authors Pharris-Ciurej ND, Cook LS , Weiss NS.
    Citations Am J Epidemiol 1999; 150: 45-6.
    PubMedID 9250171
     
    Title Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults.
    Authors Mostert MC, Verkerk AJ, van de Pol M, Heighway J, Marynen P, Rosenberg C, van Kessel AG, van Echten J, de Jong B, Oosterhuis JW , Looijenga LH.
    Citations Am J Pathol 2000; 157: 1155-1166.
    PubMedID 10211110
     
    Title Identification of the crucial region of 12p overrepresentation in testicular germ cell tumors of adolescents and adults.
    Authors Mostert MC, Verkerk AJMH, Van de Pol M, Heighway J, Marynen P, Rosenberg C, Geurts van Kessel A, van Echten J, Oosterhuis JW , Looijenga LHJ.
    Citations Am J Pathol 2000; 157: 1155-1166.
    PubMedID 7682101
     
    Title Heterogeneity in alkaline phosphatase isozyme expression in human testicular germ cell tumors. An enzyme-/immunohistochemical and molecular analysis.
    Authors Roelofs H, Manes T, Millan JL, Oosterhuis JW , Looijenga LHJ.
    Citations J Pathol 1999; 189: 236-244.
    PubMedID 10786678
     
    Title Heterogeneity in the in vitro survival and proliferation of human seminoma cells.
    Authors Olie RA, Looijenga LHJ, Dekker MC, De Jong FH, De Rooy DG , Oosterhuis JW.
    Citations Brit J Cancer 1995; 71: 13-17.
    PubMedID 10211110
     
    Title Frequent p16INK4 (MTS1) gene inactivation in testicular germ cell tumors.
    Authors Chaubert P, Guillou L, Kurt A-M, Bertholet M-M, Metthez G, Leisinger H-J, Bosman F , Shaw P.
    Citations Genes Chromosom Cancer 1995; 14: 133-144.
    PubMedID 9632138
     
    Title Genetic analysis of childhood endodermal sinus tumors by comparative genomic hybridization.
    Authors Perlman EJ, Hu J, Ho D, Cushing B, Lauer S , Castleberry RP.
    Citations Lab Invest 1989; 60: 14-20.
    PubMedID 7515656
     
    Source and Citation
    Source Atlas of Genetics and Cytogenetics in Oncology and Haematology
    Citation Desangles F, Camparo P . Testis: Germ cell tumors. Atlas Genet Cytogenet Oncol Haematol. August 1998 .
    URL : http://AtlasGeneticsOncology.org/Tumors/malegermID5005.html
    URL http://AtlasGeneticsOncology.org/Tumors/malegermID5005.html