Diagnosis and Follow-Up of
Testicular Carcinoma in situ by
DNA Image Cytometry

Heidenrich, A; Zumbé, J.; Engelmann, U.

doi:10.1159/000475013

Cited by 11 publications

(5 citation statements)

References 10 publications

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“…The high susceptibility of testicular germ cell tumours to drug-induced apoptosis appears to be the result of the overexpression of wild-type p53 and bax as well as the lack of bcl-2 protein expression (Chresta et al 1996). Furthermore, the high expression of p53 protein and the complete lack of bcl-2 oncoprotein expression in testicular carcinoma in situ cells might explain their high susceptibility to, and their eradication by, testicular irradiation (Dieckmunn et ul., 1989;Heidenreich et al 1995b).…”

Section: Discussionmentioning

confidence: 99%

“…Since testicular carcinoma in situ is considered to be the precursor lesion of all germ cell tumours (Skakkebrek et al, 1987;Dieckmann ei al., 1989: Heidenreich ei al. 1995a, and molecular genetic studies on CIS are sparse in the literature (Heidenreich et al 1995b;Kuczyk et al 1996); we also investigated the possible involvement of p53 and bcl-2 in testicular CIS.…”

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confidence: 99%

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Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and the bcl‐2 oncogene in primary testicular germ cell tumours

Heidenreich

Schenkman

Sesterhenn

et al. 1998

APMIS

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analysis of the p53 tumour suppressor gene and the bcl-2 oncogene in primary testicular germ cell tumours. APMIS 106: 90-100, 1998.The role of p53 in testicular germ cell tumours is still contradictory based on the finding of immunohistochemical overexpression at the protein level, but lack of mutations at the DNA level. In addition, p53 wild-type activity has been demonstrated in cell culture experiments. Overexpression of the proto-oncogene bcl-2 might block p53-induced apoptosis and might inhibit p53 functional activity. To clarify the apparent paradox with respect to p53 overexpression and lack of mutations, an immunohistochemical and mutational analysis of p53 and bcl-2 in TGCT was performed. Ten normal testes, 52 CIS and 151 clinical stage I nonseminomatous GCTs were included in our study.A commercially available anti-p53 polyclonal rabbit antibody and an anti-bcl-2-mouse monoclonal antibody were used to stain the 5pm sections. Staining was assessed by counting at least 500 cells from the area of the most intense staining in each tumour cell type, and this was scored semiquantitatively for intensity of staining on a 4 point scale. In addition, 30 primary GCTs were included in the mutational analysis: areas with p53 overexpression were identified and microdissected prior to DNA extraction. p53 exons 5-8 were amplified by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis. Templates demonstrating band shifts on SSCP were subjected to direct DNA sequence analysis. None of the normal testes, 32/52 (62%) CIS, and 142/151 (94%) germ cell tumours exhibited p53 overexpression. p53 expression was significantly lower in mature teratomas (0.820.2) than in other germ cell tumour components (2.821.2, p>O.OOl). PCR-SSCP did not reveal any missense mutations or deletions for the p53 gene. Bcl-2 protein expression was observed in none of the normal testes, in none of the CIS, and in 14/151 (9.3%) germ cell tumours. 13/14 germ cell tumours demonstrated bcl-2 expression only in the glandular and stromal elements of their teratomatous components whereas all other components were negative for bcl-2. Our results -p53 overexpression, lack of p53 mutations, undetectable bcl-2 -are consistent with recent in vitro studies. High susceptibilty of testicular cancer to druginduced apoptosis appears to be the result of wild-type p53 and lack of bcl-2. Radiation and chemotherapeutic insensitivity of mature teratomas might be the result of bcl-2 overexpression and lack of p53 overexpression. Therefore, chemoresistance to DNA damaging agents might be reflected by the expression of p53 and bcl-2 and it might be useful to evaluate p53 and bcl-2 in primary tumours and metastatic lesions in order to identify patients early with primary or secondary chemoresistance.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and the bcl‐2 oncogene in primary testicular germ cell tumours

Heidenreich

Schenkman

Sesterhenn

et al. 1998

APMIS

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“…Various fluorescent dyes were used to stain DNA (and/or other components) of testicular cells, and the stained cells were analyzed or sorted according to the intensity of fluorescence emission, which correlates with DNA content [11][12][13][14][15][16][17][18][19]. This technique has also been used as a diagnostic tool to assess spermatogenesis as well as development of testicular cancer in human patients [20][21][22]. However, since the adult testis consists of cells at all stages of spermatogenic differentiation, the approaches mentioned above cannot enable accurate analysis of stagespecific biochemical events and gene expression.…”

Section: Introductionmentioning

confidence: 99%

Developmental Schedule of the Postnatal Rat Testis Determined by Flow Cytometry1

Malkov

Fisher

Don

1998

Biology of Reproduction

141

138

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Analysis of the biochemical events and the genes expressed at various postnatal developmental stages in the testis of mammals is of great importance for understanding spermatogenesis in general and meiosis in particular. A prerequisite for such an analysis is the characterization of a detailed developmental schedule of the postnatal testis. In this study we used four-parameter flow cytometry analysis to determine a detailed testicular developmental schedule in rats as compared to mice. A dot plot of forward-scatter/side-scatter of testicular cell suspensions from mature animals revealed 7 distinct subpopulations within the testis. These, when analyzed by fluorescence parameters, were divided into 4 levels of fluorescence: cells containing 4d DNA, 2d DNA, and 2 levels of haploid cells. Observing the acquisition pattern of these subpopulations during postnatal development, we were able to suggest the following developmental schedule for the rat. At postnatal Days 6-7, the testis contains somatic cells and spermatogonia cells only. By Days 13-14, leptotene spermatocytes appear; by Days 17-18, zygotene spermatocytes are present; by Days 19-20 and Days 22-23, early and late pachytene spermatocytes, respectively, are seen. Haploid round spermatids first appear at Days 24-25 and elongating spermatids by Days 30-31; by Day 36, elongated spermatozoa can be found.

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“…To reduce the risk of local complications various minimally invasive techniques have been described to diagnose TIN: fine‐needle aspiration followed by DNA flow cytometry; fluorescence in situ hybridization (FISH) techniques, or in‐situ with ploidy assessments [21–24]. Currently, these methods have a sensitivity and specificity inferior to those of surgical biopsies.…”

Section: Diagnosis Of Tinmentioning

confidence: 99%

Contralateral testicular biopsy in testis cancer: current concepts and controversies

Heidenreich

2009

BJU International

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Of all patients with unilateral testis cancer, ≈5% harbour testicular intraepithelial neoplasia (TIN) in their contralateral testicle that will progress into an invasive germ cell tumour over time. The accurate diagnosis of TIN by a random two‐site surgical testis biopsy and effective therapy by local radiation has led to the concept of a contralateral screening biopsy in all patients with testis cancer. However, screening and preventive treatment are only indicated if the therapeutic outcome of the screened population is improved, and the physiological function of the affected organ is not impaired. Based on a critical review of previous reports, some drawbacks of this policy have to be considered and question the routine indication for contralateral testis biopsy: (i) all TIN‐negative patients still have to undergo meticulous follow‐up for metachronous testis cancer due to a false negative biopsy rate of 0.5–1.0%; (ii) local radiation of TIN results in irreversible infertility due to eradication of spermatogenesis; (iii) local radiation of TIN results in an impairment of endocrine Leydig cell function in 25% of the patients; (iv) therapeutic outcome and prognosis will not be improved in irradiated patients as compared to patients on surveillance; (v) local tumour resection for the management of metachronous testicular cancer represents an effective and viable option. Current reports do not support the strategy of contralateral testis biopsy in all patients with unilateral testicular germ cell tumours. According to the recommendations of the European Germ Cell Cancer Consensus Group, a testis biopsy might be offered to high‐risk patients for contralateral TIN (testicular volume <12 mL, history of cryptorchidism, age <30 years).

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Diagnosis and Follow-Up of Testicular Carcinoma in situ by DNA Image Cytometry

Cited by 11 publications

References 10 publications

Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and the bcl‐2 oncogene in primary testicular germ cell tumours

Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and the bcl‐2 oncogene in primary testicular germ cell tumours

Developmental Schedule of the Postnatal Rat Testis Determined by Flow Cytometry1

Contralateral testicular biopsy in testis cancer: current concepts and controversies

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