Alteration in age-specific risks for chromosomal trisomy by maternal serum alpha-fetoprotein and human chorionic gonadotropin screening.

Maternal serum screening for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) increases the detection rate of Down's syndrome (DS) pregnancies. To estimate the risk of a DS pregnancy for a particular woman, Wald et al. combine a trivariate function of AFP, hCG, and unconjugated oestriol with age-specific risk. Calculation of independent likelihood ratios (LRs) for AFP and hCG has allowed us to examine the predictive value of each test alone and the combination. AFP and hCG were measured in stored serum samples from 672 normal, 8 trisomy 21 (DS), 9 trisomy 18, and 2 trisomy 13 pregnancies. AFP and hCG multiples of the median (MOM) were calculated for each sample. The LRs for AFP MOM and hCG MOM were calculated and combined with age-specific risk. Of eight DS pregnancies, six had increased risk based on age and AFP. Addition of hCG detected two additional DS pregnancies. Of nine trisomy 18 pregnancies, four (44 per cent) had hCG MOM under 0.25. Three out of nine would have been classified as high risk by AFP, but none by combined AFP and hCG. Amniocentesis would have been recommended in 74 per cent of aneuploid pregnancies if both age and serum screening were used. Abandonment of amniocentesis based on age alone would have excluded two abnormal pregnancies from detection. Screening programmes should note that combined risk figures are specific for DS and do not include other trisomies. Detection of other trisomies requires inclusion of low hCG level as a discriminator and continuation of age-based testing.

Quantitative DNA patterns in human preneoplastic breast lesions.

In 12 cases of human mammary carcinoma in which a preneoplastic atypical ductal hyperplasia was also identified, quantitative DNA (QDNA) measurements of thionein-stained samples from both lesions were performed using the Cell Image Analysis 100 system. The QDNA values in the preneoplastic and neoplastic lesions from each case showed concordance (six as euploid and six as aneuploid/hyperdiploid). Such congruence suggests a stable inheritance of the somatic mutation(s) that is involved in carcinogenesis and that affects ploidy. If this relationship between concurrent preneoplasia and neoplasia in the ipsilateral breast is confirmed, it offers the possibilities of (1) identifying individuals at risk for developing neoplasias with defined biologic characteristics and (2) developing therapeutic regimens more appropriate to the risk assessment of each patient. It may be possible to conceive of a rational preventive regimen for cancer of the breast.