Abnormal infantile germ cells and development of carcinoma‐in‐situ in maldeveloped testes: a stereological and densitometric study

Müller, Jørn

doi:10.1111/j.1365-2605.1987.tb00354.x

Cited by 33 publications

(19 citation statements)

References 84 publications

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“…Probably, a combination of high LH levels, high intratesticular androgen levels coupled with lower androgen activity, and high oestradiol levels are necessary for TC development and progression. This hypothesis fits well with the observation that subjects with AIS due to mutations in the AR gene are at high risk of developing TC (Mu¨ller 1987). On the contrary, subjects with Kallmann's syndrome having hypogonadotrophic hypogonadism never develop TC.…”

Section: Discussionsupporting

confidence: 75%

Molecular analysis of the androgen receptor gene in testicular cancer

Garolla

Ferlin²,

Vinanzi³

et al. 2005

Endocr Relat Cancer

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Testicular cancer (TC) is the most common solid tumour in white males aged 20-34 years, and its incidence has doubled over the past 40 years. Some risk factors for TC have been proposed, such as cryptorchidism, infertility and testicular dysgenesis. However, the causes of TC remain still largely unknown. Recently a genetic basis for TC has been proposed, but specific genetic alterations have not been identified. The risk of TC is markedly increased in subjects with androgen insensitivity and some authors have suggested that mutations in the androgen receptor (AR) gene or disorders of CAG and GGC repeats could be related to TC. However, definitive data have not been produced. In this study, we analysed the AR gene for mutations and CAG and GGC triplets in exon 1 in 123 patients affected by TC. In three patients (2.3%) we found a mutation in the AR gene, two of which represent a novel mutation. Evaluation of CAG and GGC repeat numbers showed no difference with respect to controls when these variables were analysed separately. However, when joint distributions of CAG and GGC were considered, we found that the combination CAG=20/ GGC=17 was significantly more frequent in TC patients (8.1%) with respect to controls (1.7%, P<0.05). Furthermore, we observed that in TC subjects, differently from controls, the joint analysis of CAG and GGC showed a statistically significant dependence among these variable repeats. In conclusion, our data show for the first time a high prevalence of AR gene mutations in patients affected by TC and suggest that some CAG/GGC combinations might be more frequently associated with an increased risk of TC.Endocrine-Related Cancer (2005) 12 645-655

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Section: Discussionsupporting

confidence: 75%

Molecular analysis of the androgen receptor gene in testicular cancer

Garolla

Ferlin²,

Vinanzi³

et al. 2005

Endocr Relat Cancer

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“…Further characterization of the functional deficit in these patients may shed light in this regard. It is also notable that the isolation of the P390S mutation in a patient with testicular cancer (31) is consistent with the observation that AIS is a clear risk factor for this malignancy (41,42). Although the exact basis for this association is unclear, elevated luteinizing hormone levels, as observed in AIS, have been implicated in testicular cancer (43).…”

Section: Defective Sumoylation As the Cause Of Ar-based Diseases-supporting

confidence: 67%

The in Vivo Role of Androgen Receptor SUMOylation as Revealed by Androgen Insensitivity Syndrome and Prostate Cancer Mutations Targeting the Proline/Glycine Residues of Synergy Control Motifs

Mukherjee

Cruz-Rodríguez

Bolton

et al. 2012

Journal of Biological Chemistry

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“…Although definitive proof is still lacking, it is generally assumed that the development of TGCT is under endocrine control, and a combination of high FSH and LH, coupled with unbalanced androgen/oestrogen levels are key events (Garolla et al 2005, Rajpert-De Meyts 2006). This condition is exemplified by the androgen insensitivity syndrome caused by mutations in the androgen receptor gene, which represents a well-recognised risk factor for TGCT (Muller 1987, Rajpert-De Meyts 2006. Clinical conditions associated with a higher risk of TGCT (cryptorchidism, testicular atrophy and infertility) are often characterised by increased plasma concentrations of FSH, whereas situations with low gonadotrophin levels (such as hypogonadotrophic hypogonadism) never develop TGCT.…”

Section: Discussionmentioning

confidence: 99%

“…Probably, a combination of high LH and FSH levels, high intratesticular androgen levels coupled with lower androgen activity, and high oestradiol levels are necessary for TC development and progression (Garolla et al 2005, Rajpert-De Meyts 2006. Such a hormonal combination is seen for example in patients with androgen insensitivity syndrome (Muller 1987, Rajpert-De Meyts 2006, which has a high risk of TC. On the contrary, subjects with Kallmann's syndrome having hypogonadotrophic hypogonadism never develop TC.…”

Section: Introductionmentioning

confidence: 99%

Analysis of single nucleotide polymorphisms of FSH receptor gene suggests association with testicular cancer susceptibility

Ferlin¹,

Pengo²,

Selice³

et al. 2008

Endocrine Related Cancer

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The development of testicular germ cell tumour (TGCT) is believed to be under endocrine control but definitive proofs are lacking. Follicle stimulating hormone (FSH) levels are increased in numerous conditions associated with increased risk of TGCT and single nucleotide polymorphisms (SNPs) in the FSH receptor (FSHR) gene influence the sensitivity of the receptor to FSH. However, a possible effect of FSH on testicular carcinogenesis has never been explored. In order to analyse the possible association of FSHR polymorphisms with TGCT, we studied 188 TGTC cases and 152 controls for 12 FSHR SNPs. Only four SNPs were found to be informative, represented by two polymorphisms in exon 10 (Ala307Thr and Ser680Asn), and two polymorphisms in the promoter region (K114 T/C and K29 G/A). Differences in haplotype distribution were seen between TGCT cases and controls. In particular for non-seminoma, the Ala307/Ser680 allele lowers the risk of the disease, alone (PZ0.014, relative risk 0.73; 95% confidence interval 0.57-0.92), or in combination with the K29 G allele and/or the K114 T allele. This study suggests for the first time that FSHR gene polymorphisms modulate susceptibility to TGCT. The variants with higher activity of the FSHR are associated with higher risk, suggesting a role for FSH in the carcinogenesis of this tumour.

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Abnormal infantile germ cells and development of carcinoma‐in‐situ in maldeveloped testes: a stereological and densitometric study

Cited by 33 publications

References 84 publications

Molecular analysis of the androgen receptor gene in testicular cancer

Molecular analysis of the androgen receptor gene in testicular cancer

The in Vivo Role of Androgen Receptor SUMOylation as Revealed by Androgen Insensitivity Syndrome and Prostate Cancer Mutations Targeting the Proline/Glycine Residues of Synergy Control Motifs

Analysis of single nucleotide polymorphisms of FSH receptor gene suggests association with testicular cancer susceptibility

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