NEW ORLEANS--A test based on the newly developed monoclonal antibody NMP179 can detect both low-grade and high-grade cervical dysplasia, according to results presented at the 89th annual meeting of the American Association for Cancer Research. The developers believe the test might one day be used as a supplement to the Pap smear.
False-negative rates for the Pap smear are as high as 30%. "We believe that the Pap smear alone cannot reliably predict the behavior of all lesions because of its reliance on morphology alone," Susan K. Keesee, PhD, manager of cell biology at Matritech, Inc., Newton, Massachusetts, said in an interview with Oncology News International. In contrast, the NMP179 test detects a nuclear matrix protein named CvC-3 that is produced by cervical carcinomas but not by normal cervical tissue.
The results presented at the meeting were from a blind preclinical feasibility study. The researchers first chose a target antigen by comparing nuclear matrix proteins from normal cervical tissue with proteins from tumors of patients with squamous cell carcinoma.
They found that the CvC-3 protein was expressed by all of the tumors (20 of 20) and none of the normal tissue (0 of 10). The investigators then developed several antibodies to CvC-3 and chose the most promising one, NMP179, for further testing.
In the tests, they obtained 322 cervicovaginal specimens from two hospitals. After preparation, the samples were stained and assayed for CvC-3 using the NMP179 antibody. The test detected the one case of squamous cell carcinoma, all 30 of the high-grade squamous intraepithelial lesions, and 48 (78.7%) of the 61 low-grade intraepithelial lesions.
However, the NMP179 antibody also produced positive results for many of the normal control samples: 18 (60%) of 30 samples with benign cellular changes and 51 (39.5%) of 129 samples diagnosed as within normal limits.
Matritech, Inc., is now looking for an image-analysis company to work with to automate the assay. "We believe the perfect symbiosis would be the combination of computer-assisted image analysis of morphologic change and a probe like ours, which we believe is detecting a molecular event that is related to progression," Dr. Keesee said. "Now we have to conduct a study using clinical outcomes as an endpoint, to determine the true efficacy of NMP179."