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Cancer risk increases for patients who undergo transplant
Newsdesk Cancer risk increases for patients who undergo transplant A nationwide Swedish cohort study of 5931 transplant patients has shown a four-fold excess risk of cancer and has also quantified the increased risk for a wider range of specific cancers than previously known (Br J Cancer 2003: 89: 1221–27). The researchers studied 3592 men and 2339 women who had received transplants between 1970 and 1997. Of these 84·3% received kidney transplants; the rest underwent liver, heart, lung, pancreas, or multiple transplants. Data from the Swedish Cancer Registry enabled cancer incidence rates for this group to be established and compared with those of the general population. In accordance with previous findings, nonmelanoma skin cancer and lip cancer showed the highest increased relative risk, rising 56 and 53 times, respectively, in transplanted patients. Substantial excess risks for cancer of the vulva (26-fold increase), vagina
(16-fold) and anus (10-fold) were new findings. “The pattern of cancers which emerged made us think about the underlying causes”, says first-author Johanna Adami, Karolinska Institute, Stockholm, Sweden. “Because cancers of the anus, vulva, and vagina are thought to be caused by viruses, we considered whether viruses might be involved in the increased risk. The immune system is turned upside down when people undergo transplants. As well as having an organ from another person in their system, patients get very potent immunosuppressant medication—both these factors can activate viruses”. The absence of increased risk for cervix or uterine cancers contradicts this viral hypothesis. However, another group of Swedish researchers propose that increased immunosuppression in the cervix might have evolved to avoid destroying sperm,
thus rendering post-transplant immunosuppression insignificant (Cancer Immunity 2003; 3: 6–8). Didier Ducloux, Saint Jacques Hospital, Besançon, France, comments: “The main points of interest are the existence of a national control population, long duration of followup, and exhaustiveness of the registry”. He believes that as transplant patients survive longer and immunosuppressive drugs increase in potency, it is important to know how their cancer risk evolves. “Whether changes in patient phenotypes and immunosuppressive regimens over time influence the risk of cancer in this population remain important challenges for future epidemiological studies.” Adami’s team are now planning to analyse the relation between different immunosuppressive regimens and cancer incidence by site. Claudia Orellana
Subclinical metastases identified from stored biopsy samples
THE LANCET Oncology Vol 4 November 2003
Marker expression in the positive SLNs was 89%, 92%, 35%, and 43% for the four markers. The corresponding marker expression in negative SLNs was 40%, 33%, 5% and 13%. 25% of
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
© James King-Holmes/Science Photo Library
A molecular technique to identify multiple RNA markers that correlate with the presence of melanoma micrometastases has proved itself useful for clinical practice. The test could soon be used routinely to identify patients at high risk of recurrence, even though their biopsy samples look clear using standard histology. “We have shown that a multimarker-RT-PCR assay can detect molecular risk factors in archived samples of paraffin-embedded sentinel lymph nodes (SLNs) very accurately”, comments senior author David Hoon (John Wayne Cancer Institute, CA, USA). The group first confirmed the ability of the assay to detect four melanoma-associated antigen markers in archived metastatic tumour tissue and then tested archived samples from 77 patients. Assay results were compared with the clinical history of the patients: of the 77 samples, 37 were positive and 40 were negative when examined histopathologically using antibodies, which are 10–30% more sensitive than conventional staining.
Subclinical metastases identified with PCR.
patients with negative immunohistochemistry had high expression of at least two markers; clinical histories showed that 80% of them developed a recurrence. At a median follow up of 55 months, patients with negative immunohistochemistry results, and expression of one or no markers, were
significantly more likely to be disease free and had better overall survival than patients with negative results who expressed two or more markers (J Clin Oncol 2003; 21: 3566–72). Hoon’s technique is particularly valuable because it allows investigation of paraffin-embedded samples as well as fresh and frozen sections. “Several samples can be assayed at once and the approach makes it possible to integrate new markers when they are identified”, adds Hoon. However, Faris Abuzahra (RWTH Aachen, Germany) warns that before the assay can be used routinely, it needs to be evaluated in a multicentre study. “Reproducibility, sensitivity and, most importantly, specificity of any new technique should be critically studied”, he comments. “Identifying patients at increased risk of relapse is important as some may be eligible for adjuvant therapy trials”, says Hoon. Abuzahra agrees, pointing out that such patients could be given high-dose interferon alfa, which known to improve disease-free survival. Kathryn Senior
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
651
(16-fold) and anus (10-fold) were new findings. “The pattern of cancers which emerged made us think about the underlying causes”, says first-author Johanna Adami, Karolinska Institute, Stockholm, Sweden. “Because cancers of the anus, vulva, and vagina are thought to be caused by viruses, we considered whether viruses might be involved in the increased risk. The immune system is turned upside down when people undergo transplants. As well as having an organ from another person in their system, patients get very potent immunosuppressant medication—both these factors can activate viruses”. The absence of increased risk for cervix or uterine cancers contradicts this viral hypothesis. However, another group of Swedish researchers propose that increased immunosuppression in the cervix might have evolved to avoid destroying sperm,
thus rendering post-transplant immunosuppression insignificant (Cancer Immunity 2003; 3: 6–8). Didier Ducloux, Saint Jacques Hospital, Besançon, France, comments: “The main points of interest are the existence of a national control population, long duration of followup, and exhaustiveness of the registry”. He believes that as transplant patients survive longer and immunosuppressive drugs increase in potency, it is important to know how their cancer risk evolves. “Whether changes in patient phenotypes and immunosuppressive regimens over time influence the risk of cancer in this population remain important challenges for future epidemiological studies.” Adami’s team are now planning to analyse the relation between different immunosuppressive regimens and cancer incidence by site. Claudia Orellana
Subclinical metastases identified from stored biopsy samples
THE LANCET Oncology Vol 4 November 2003
Marker expression in the positive SLNs was 89%, 92%, 35%, and 43% for the four markers. The corresponding marker expression in negative SLNs was 40%, 33%, 5% and 13%. 25% of
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
© James King-Holmes/Science Photo Library
A molecular technique to identify multiple RNA markers that correlate with the presence of melanoma micrometastases has proved itself useful for clinical practice. The test could soon be used routinely to identify patients at high risk of recurrence, even though their biopsy samples look clear using standard histology. “We have shown that a multimarker-RT-PCR assay can detect molecular risk factors in archived samples of paraffin-embedded sentinel lymph nodes (SLNs) very accurately”, comments senior author David Hoon (John Wayne Cancer Institute, CA, USA). The group first confirmed the ability of the assay to detect four melanoma-associated antigen markers in archived metastatic tumour tissue and then tested archived samples from 77 patients. Assay results were compared with the clinical history of the patients: of the 77 samples, 37 were positive and 40 were negative when examined histopathologically using antibodies, which are 10–30% more sensitive than conventional staining.
Subclinical metastases identified with PCR.
patients with negative immunohistochemistry had high expression of at least two markers; clinical histories showed that 80% of them developed a recurrence. At a median follow up of 55 months, patients with negative immunohistochemistry results, and expression of one or no markers, were
significantly more likely to be disease free and had better overall survival than patients with negative results who expressed two or more markers (J Clin Oncol 2003; 21: 3566–72). Hoon’s technique is particularly valuable because it allows investigation of paraffin-embedded samples as well as fresh and frozen sections. “Several samples can be assayed at once and the approach makes it possible to integrate new markers when they are identified”, adds Hoon. However, Faris Abuzahra (RWTH Aachen, Germany) warns that before the assay can be used routinely, it needs to be evaluated in a multicentre study. “Reproducibility, sensitivity and, most importantly, specificity of any new technique should be critically studied”, he comments. “Identifying patients at increased risk of relapse is important as some may be eligible for adjuvant therapy trials”, says Hoon. Abuzahra agrees, pointing out that such patients could be given high-dose interferon alfa, which known to improve disease-free survival. Kathryn Senior
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
651