BioWorld International Correspondent

LONDON - 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 the biotechnology company DakoCytomation, of Glostrup, also in Denmark, to develop the test further.

Christina Hoei-Hansen, a physician at the Rigshospitalet in Copenhagen, told 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 titled "A sub-fertile patient diagnosed with testicular carcinoma in situ by immunocytological staining for AP-2gamma in semen samples: Case report."

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 before it has spread, more than 90 percent 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 that idea. The researchers asked a group of 12 patients with testicular cancer to give semen samples, before they underwent surgical removal of the affected testis. A group of control patients also took part. They included seven men who already had had a testicle removed because of testicular cancer, 12 men with other diseases or other tumors, 59 patients under investigation for subfertility, 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 the U.S. company Santa Cruz Biotechnology Inc.

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 percent. 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."