The higher incidence of squamous cell carcinoma in renal transplant recipients is associated with increased telomere lengths.
The incidence and aggressiveness of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma (SCC), in immunocompromised renal transplant recipients (RTRs) is dramatically higher (up to 100-fold) compared with the normal population. SCC lesions are also predominant in RTRs, in contrast to the normal population where basal cell carcinoma is more common. The mechanisms underlying this phenomenon are unknown, but effective treatments for these skin tumors would have a significant impact upon morbidity in this group of patients. The fundamental role of telomeres and telomerase in the development of most human cancers, including melanoma, is well established, but very few reports have assessed their function during the onset of nonmelanoma skin cancer. To assess whether telomere maintenance plays any role in the increased incidence of SCC in renal transplant patients, we analyzed both the telomere lengths and telomerase expression levels in 44 SCCs and 22 Bowen's disease (BD) samples (carcinoma in situ) from RTRs and nontransplant patients. Our findings provide statistically significant evidence that the telomeres are consistently longer in both BD RTR and SCC RTR lesions compared with their nontransplant counterparts. We also show by immunohistochemistry that there is a trend toward higher telomerase levels in both the BD RTR and SCC RTR lesions, although this was not statistically significant. Our data thus suggest that telomere lengthening may possibly be an early event in the development of SCC in renal transplant patients and demonstrate that telomere maintenance mechanisms should be further evaluated with respect to developing a future therapeutic strategy for these cancers.
Perrem
Kilian
K
Molecular Oncology Laboratory, Department of Pathology, The Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. kperrem@rcsi.ie
Lynch
Ailish
A
Conneely
Maura
M
Wahlberg
Henrik
H
Murphy
Gillian
G
Leader
Mary
M
Kay
Elaine
E
D001483:Base Sequence; D001913:Bowen's Disease / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D012878:Skin Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis; D016615:Telomere / Q000235:genetics*
C509186:TERT protein, human; D019098:Telomerase