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Cancer Resources > Cancer News > Cancer News from Reuters > Reuters Cancer News > 2000 > June

PTEN loss marks early endometrial precancers

WESTPORT, Jun 14 (Reuters Health) - Single PTEN-negative glands in endometria exposed to estrogen are the earliest signs of endometrial carcinogenesis, according to a team of international researchers.

Dr. George L. Mutter from Brigham and Women's Hospital, Boston, Massachusetts and a multicenter team studied endometrial cancer and precancer tissue for alterations in PTEN. "We did this at two different levels. The first was looking for mutations of the gene at the DNA level and the second was to look at the ability of the gene to make RNA and finally protein," Dr. Mutter told Reuters Health.

The team reports in the June 7th issue of the Journal of the National Cancer Institute that PTEN mutations occurred in 83% of endometrioid endometrial adenocarcinomas and in 55% of precancers. "We think," Dr. Mutter said, "that this is because it is specifically the endometrial cancers that go through a precancer phase that are likely to have PTEN mutations."

They researchers also studied a group of women who had slightly protracted intervals of nonopposed estrogen exposure. As Dr. Mutter pointed out, women exposed to estrogens in the absence of progesterone are at 5- to 7-fold increased risk for endometrial cancer.

"When we looked at their endometria we found isolated, very small areas of individual glands, typically single glands, that stopped expressing the PTEN protein. And these were surrounded, in most cases, by glands that did express the PTEN protein. When we look at precancers that can be recognized we find that three fourths of these precancers do not express the PTEN protein and we found them in about 30% of women," Dr. Mutter explained.

"We think what we are seeing is the very earliest phases of the road to cancer," he said. These lesions start as single cells really and grow as a single gland under estrogen-rich conditions. The researchers believe that estrogen may prevent the normal shedding of the endometrium, and estrogen may also make the mutation functionally advantageous.

The implication, according to Dr. Mutter, is that PTEN function is critical in the earliest phases of the disease. "We have pushed it back to a time even earlier than we had realized. This is a lesion that exists before it becomes a precancer. Here we are able to look two or three times earlier in terms of disease burden. So if you had a drug that would make a PTEN mutation nonadvantageous you would be able to prevent even the precancers."

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