A startling case in Japan has confirmed that pregnant women with cancer can pass the disease to their fetuses. These transmissions, normally blocked by the placenta, are rare, so the work likely won't change how doctors screen or care for pregnant women. But scientists say the case could help illuminate how cancer foils the body's immune system.
In early 2007, a 28-year-old Japanese woman gave birth to a girl. Thirty-six days later, the mother was hospitalized with vaginal bleeding, which became uncontrollable. Doctors diagnosed leukemia, and she soon died. The baby developed normally until age 11 months, when a huge tumor appeared in her cheek. A biopsy determined the cancer was not sarcoma--a cancer of certain connective tissues--but a leukemic tumor somehow trapped in the child's cheek.
The doctors alerted cell biologist Mel Greaves of the Institute of Cancer Research in Sutton Surrey, United Kingdom, who studies transmissible cancers. Scientists had suspected mother-to-fetus cancer in other cases with strong circumstantial evidence (especially with leukemia and melanoma, which both metastasize readily). But no one had done genetic tests to prove the cancer had grown from a single source and wasn't just an unfortunate coincidence.
In their investigation, Greaves and colleagues discovered incipient cancer cells in routine blood samples taken from the child at birth, strongly suggesting that the transmission happened in utero. They also examined a DNA sequence unique in each case of leukemia, the BCR-ABL1 sequence. It was identical in mother and daughter. Finally, tests showed the child's cancer cells were almost all maternal cells, with no genetic material from the father. This indicated that the transmission path was mother to fetus, not the reverse. The team lays out its evidence in a paper published online 12 October in the Proceedings of the National Academy of Sciences.
Greaves and colleagues also determined how cancer survived inside the fetus, whose immune system should have destroyed the mother's cells. They found that the cancer cells were missing a large region from a stretch of the sixth human chromosome known as 6p, which produces surface markers that immune cells latch on to. In short, Greaves says, "the cancer succeeded because it was immunologically invisible."
Knowing the molecular details of how the cells evaded detection will help scientists probe how other cancers slip by our immune system, says Howard Weinstein, a pediatric cancer specialist at Massachusetts General Hospital in Boston.
Despite the findings, mothers shouldn't panic, says Greaves. With only a few dozen cases of mother-fetus cancer transmission reported since the first, in 1866, the risk for pregnant women is minimal, he says. And transferring advanced cancer to infants is not necessarily fatal--the Japanese girl was successfully treated and is still alive. But Greaves says his team's work questions the assumption that the placenta provides a wholly effective barrier between mothers and fetuses. "I'm more inclined to think that maybe cells get by in modest numbers all the time," he says. "You can learn a lot from very odd cases in medicine."
By Sam Kean
ScienceNOW Daily News
13 October 2009