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We have analyzed 95 blood- and 25 paraffin-derived DNA samples of 120 individuals from Switzerland (MEN 2 family members and patients with medullary thyroid carcinoma or pheochromocytoma) for the presence of RET protooncogene mutations in exons 10, 11, 13, 14 and 16, where recently germline point mutations have been identified in more than 95% of patients with MEN 2A, familial medullary thyroid carcinoma (FMTC) and MEN 2B. Molecular DNA screening of samples was performed by non-radioactive single strand conformation polymorphism (SSCP) and heteroduplex gel electrophoresis method followed by mutation analysis of PCR products by direct cycle sequencing using an automated DNA sequencer. We identified 12 MEN 2A/FMSC and 6 MEN 2B families with 29 gene carriers. Ten different types of mutations were identified in the MEN 2A/FMTC families (620 Cys-->Arg, 618 Cys-->Ser, Gly, 611 Cys-->Tyr; 634 Cys-->Arg, Tyr, Trp, Phe, Ser, Gly) and all 6 MEN 2B families had a 918 Met-->Thr point mutation. Our results indicate that PCR-based DNA testing for RET point mutations is a rapid, accurate and reproducible method of identifying MEN 2 gene carriers using blood or tissue DNA. Early detection of gene carriers allows preventive thyroidectomy without neck dissection or parathyroid transplantation, and non-gene carriers can be released from biochemical testing. Furthermore, it is shown that the distribution and localization of RET mutations in MEN 2 families from Switzerland concur with combined results of larger series and that a "founder effect" of MEN 2 can be excluded for this country.

The hormonally induced changes in the breast during pregnancy make the diagnosis of breast cancer difficult. Furthermore, examinations during pregnancy tend to concentrate only on the pregnancy itself. In this report the clinical, pathological and immunohistochemical results from 7 patients with breast cancer during pregnancy are presented. All women first noticed the tumor by self-examination. The time periods between discovery of the tumor and medical treatment were between 4 and 22 weeks. An overexpression of c-erbB-2-oncogene coded transmembrane protein p185 could be demonstrated in 4 cases. Of the seven patients, 5 have already passed away. Three of the deceased had p185-positive tumors, and died 4, 8 and 21 months after diagnosis. The two p185-negative patients lived 34 and 65 months post diagnosis. Despite the small amount of cases presented, a trend can be seen that p185 may be an additional prognostic factor for breast cancer in pregnancy.