Renal transplantation-related risk factors for the development of uterine adenomatoid tumors

Mizutani, Teruyuki; Yamamuro, Osamu; Kato, Noriko; Hayashi, Kazumasa; Chaya, Junya; Goto, Norihiko; Tsuzuki, Toyonori

doi:10.1016/j.gore.2016.05.003

Cited by 12 publications

(10 citation statements)

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“…Of note is a growing number of case reports documenting an association of adenomatoid tumors arising in patients who are immunosuppressed for treatment of autoimmune disease or following allograft organ transplantation, and rare examples of immunosuppressed patients with giant or multiple adenomatoid tumors have also been reported. 7 – 11 This suggests a potential link between adenomatoid tumors and deregulated cytokine signaling pathways within mesothelial cells. Herein, we report the discovery of a defining genetic cause of adenomatoid tumors that may help to explain this association of adenomatoid tumors with immune dysregulation.…”

Section: Introductionmentioning

confidence: 99%

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation

et al. 2018

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Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs). These mutations all clustered into one of five recurrent hotspots within the WD40 repeat domains at the C-terminus of the protein. Functional studies in vitro revealed that expression of mutant but not wildtype TRAF7 led to increased phosphorylation of nuclear factor-kappa B (NF-kB) and increased expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation. Immunohistochemistry demonstrated robust L1CAM expression in adenomatoid tumors that was absent in normal mesothelial cells, malignant peritoneal mesotheliomas, and multilocular peritoneal inclusion cysts. Together, these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation that drives aberrant NF-kB pathway activation.

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Section: Introductionmentioning

confidence: 99%

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation

et al. 2018

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“…Specific immunosuppressive agents may affect the pathobiology of AT. PSL, which was administered to all the immunosuppressed AT patients in our series and those in previous reports, could be a candidate. However, PSL is the most commonly used immunosuppressive agent, and it might just be a confounding factor.…”

Section: Discussionmentioning

confidence: 67%

“…Of note, multifocal AT was also identified in non-immunosuppressed patients. Recently, Mizutani et al 19 examined 1094 hysterectomy specimens and identified ATs in 10 of 14 (71.4%) renal transplant recipients who were under immunosuppressive therapy. These authors reported a significant correlation between the occurrence of AT and the length of time on dialysis (P = 0.047).…”

Section: Discussionmentioning

confidence: 99%

“…However, it is not clear whether there is a qualitative difference between single nodular AT and diffuse AT, especially with respect to the background immunosuppressive status. A recent study from Japan that focused on the incidence of uterine AT in renal transplant recipients under immunosuppressive therapy revealed a strikingly high incidence of 71.4% . In the report, the nodularity and diffuseness of AT was not mentioned.…”

Section: Introductionmentioning

confidence: 91%

“…A recent study from Japan that focused on the incidence of uterine AT in renal transplant recipients under immunosuppressive therapy revealed a strikingly high incidence of 71.4%. 19 In the report, the nodularity and diffuseness of AT was not mentioned.…”

Section: Introductionmentioning

confidence: 98%

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