Microheterogeneity of alpha-fetoprotein (AFP) present in the sera of 76 patients was studied by lectin affino-immunoelectrophoresis. Seventeen patients had benign liver disorders and the remaining 59 patients were treated for primary or secondary liver cancer or yolk sac tumour. By means of Con A, AFP was divided into two variants, while lentil lectin (LCA) made it possible to separate AFP in three variants. In some patients the relative concentrations of Con A and LCA AFP variants were similar; these patients were believed to produce AFP of the same 'profile'. Fourteen AFP profiles were observed by estimation of the area enclosed by precipitates corresponding to respective AFP variants. It was also possible to estimate the AFP profile on the basis of a simple visual analysis of the electrophoretic plates. The obtained results indicate that the AFP profiles of patients with cancer were variable. In spite of variations of the AFP profile in cancer patients, in most cases it was possible to differentiate primary liver cancer from yolk sac tumour and from liver metastases of cancer. In addition, in two-thirds of hepatoma patients the AFP profile was different from the profile observed in patients with benign liver disorders.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatinbased chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB -IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P ¼ 0.005) or the only (in FIGO IIIC, P ¼ 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(À) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P ¼ 0.047) and by BCL2 expression in the TP53(À) group (P ¼ 0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P ¼ 0.049); its loss was found with advancing FIGO stage (P ¼ 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.

Three di erent novel BRCA1 mutations, ®ve independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identi®ed among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were ®rst found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT ± PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and signi®cance of di erent BRCA1 variants and mutations.Keywords: BRCA1; mutations and variants; SSCPheteroduplex analysis; Polish women; positive family history IntroductionApproximately one in ten women in western countries will develop breast cancer during their lifetime . In most cases the disease is sporadic; however, some 5 ± 10% of women with breast cancer inherit increased susceptibility to the disease (Claus et al., 1991). Within this fraction of breast cancer the germline mutations in BRCA1 (Miki et al., 1994) and BRCA2 genes most frequently form a favorable genetic background for the disease. Also at increased risk are the carriers of one abnormal allele of the ataxia telangiectasia gene (Swift et al., 1991), the carriers of rare minisatelite allele at the HRAS1 locus (Krontiris et al., 1993) and the members of Li Fraumeni families with germline mutation in the p53 gene (Srivastava et al., 1990).The BRCA1 gene located on chromosome 17q21 (Hall et al., 1990) is also linked to hereditary ovarian cancer (Narod et al., 1991). More than 400 BRCA1 sequence variants have been identi®ed thus far and deposited in Breast Cancer Information Core Database (Friend et al., 1995) which now contains about 150 di erent cancer predisposing mutations. Most of this knowledge comes from studies of breast and breastovarian cancer families. Therefore the known mutations are probably biased towards those with more severe e ects on phenotype. It is expected that less expressive mutations will be identi®ed when studies expand and include women with less profound family history and women from the general population. It is also very likely that the inciden...

Thyroid carcinoma appears to be an ongoing and increasing problem in the children and adolescents of our region, and it is developing more intensively when compared, both to other parts of Poland and to previous statistics (2000 vs. 1985; P<0.002). Iodine deficiency and radiation resulting from the Chernobyl disaster might be important risk factors in the development of thyroid carcinoma in the young population analysed in our region in the period since 1994. The high percentage of follicular carcinoma and follicular adenoma with an undetermined prognosis (19 out of 46) indicates that the long-term iodine deficiency in our region may be more significant in the pathogenesis of malignant transformation than has previously been postulated.