Diagnostics & Imaging Week Correspondents

A screening test to detect early testicular cancer by analyzing a semen sample could be available soon. Researchers in Denmark have shown that the new test makes it possible to diagnose the disease before it has spread outside the testicle.

The Danish group is collaborating with DakoCytomation (Glostrup, Denmark) to develop the test further.

Christina Hoei-Hansen, a physician at the Rigshospitalet (Copenhagen), told Diagnostic & Imaging Week's sister publication, BioWorld International: "These are very preliminary results and we need to do studies in many more patients before this test becomes available. Eventually, we hope to be able to use the test to screen those men at higher risk of testicular cancer for example, those with low sperm counts, those who have a close relative who has had testicular cancer, and those with a history of undescended testes."

Hoei-Hansen, together with colleagues Niels Skakkebaek and Ewa Rajpert-De Meyts, reported the study in a paper in Human Reproduction.

Testicular cancer is the most common cancer in men aged between 20 and 39. There are more than 13,000 cases diagnosed each year in Europe. If the cancer is detected early, before it has spread, more than 90% of cases can be cured.

For that reason, researchers have been searching for ways of diagnosing pre-invasive testicular carcinoma in situ (CIS) at a stage long before symptoms appear. Last year, Hoei-Hansen and other colleagues published the results of a genome-wide gene-expression profiling study of CIS cells. They found several genes that are expressed in CIS and in embryonic germ cells, but not in adult germ cells. One of those genes encodes the protein called transcription factor activator protein-2, or AP-2gamma.

Further work by the group established that AP-2gamma helps regulate cell differentiation, and has a possible role in oncogenesis. The protein could act, the group concluded, as a marker for testicular CIS.

The latest study was designed to test out that idea. The researchers asked a group of 12 patients with testicular cancer to give semen samples for testing, before they underwent surgical removal of the affected testis. A group of control patients also took part. They included seven men who had already had a testicle removed because of testicular cancer, 12 men with other diseases or other tumors, 59 patients under investigation for sub-fertility, and a group of healthy controls recruited from young men attending the department for other reasons.

Semen samples were collected and fixed on slides before immunocytochemical staining with monoclonal anti-AP-2gamma antibody manufactured by Santa Cruz Biotechnology (Santa Cruz, California).

Two investigators, not knowing which samples came from which donors, then examined the slides, using an unstained semen sample and a stained sample of known AP-2gamma-positive cells. The slides were scored as positive or negative according to predetermined criteria.

Of the 12 patients with testicular cancer, five scored positive, giving a sensitivity of 42%. Out of the remainder, one of the patients who was being investigated for infertility also scored positive.

That man, aged 23, had attended the clinic for a sperm count, as he and his partner had been trying to get pregnant for 18 months. After having detected AP-2gamma-positive cells in his semen sample, Hoei-Hansen and her colleagues carried out a range of investigations, culminating in bilateral testicular biopsies with the patient's consent.

On the patient's left side, numerous seminiferous tubules contained CIS. He had the left testicle removed surgically, and had no further treatment. He and his partner later conceived a child naturally.

Skakkebaek, head of the University Department of Growth and Reproduction at the Rigshospitalet, said, "To our knowledge, this is the first report of the diagnosis of testicular cancer at the pre-invasive CIS stage in a semen sample from a young patient with suspected infertility."

Orchid launches new scrapie test kit

Orchid BioSciences (Princeton, New Jersey), a worldwide provider of identity DNA testing services, has reported the launch of a new testing kit for scrapie susceptibility based on what it described as its "highly accurate and robust proprietary genotyping assay." Terming itself the largest provider of scrapie susceptibility genotyping in the world, Orchid said it already has used the assay to genotype more than 1.3 million sheep in its UK-based, high-throughput scrapie susceptibility testing service.

Scrapie is a fatal transmissible spongiform encephalopathy that affects sheep worldwide and, according to Orchid, "has the potential to cause significant economic losses to farmers through the destruction of infected animals and by affecting confidence in the safety of the food supply."

The company said the new kit has been designed for customers with lower-throughput testing needs who want to benefit from the accuracy of this approach when conducting sheep genotyping in their own laboratories.

David Hartshorne, commercial director of Orchid Europe (Abingdon, UK), said, "This new offering reinforces our focus on exceptional service, whereby we work with our customers to determine the most practical and cost-effective scrapie genotyping solution for their needs, whether it be conducted in our facility or in their own laboratory."

European Union legislation requires countries to introduce compulsory scrapie genotyping programs beginning in April.

Orchid also reported that it has signed an agreement with Prion Diagnostica (Milan, Italy) to commercialize this new scrapie susceptibility testing kit in that country. Prion develops diagnostic products and services in a number of different veterinary and food safety applications and is a leading provider of rapid diagnostic tests for bovine spongiform encephalopathy ("mad cow" disease).

Italy has an estimated sheep population of more than 11 million and, like most European countries, has occasionally found prion-infected sheep in its flocks.

Since 2001, Orchid has been a supplier of genotyping services to UK sheep farmers under the government's National Scrapie Plan, which is designed to help farmers breed sheep with reduced susceptibility to scrapie. Scientists have discovered a number of genetic variations that affect an individual sheep's susceptibility to scrapie. By selecting those sheep with high genetic resistance as breeding stock, over time farmers expect to produce flocks with greatly reduced vulnerability to the condition.

Orchid also is the exclusive genotyping supplier to the Northern Ireland Scrapie Plan and provides a commercial testing service directly to farmers in the UK. It established its European headquarters in 2001 through the acquisition of Cellmark Diagnostics, one of the world's first commercial DNA testing laboratories.