[Reevaluation of cytological smears in patients with cervical cancer. Regional quality assurance program with the cooperation of the Austrian Society for Cytology, the Carinthian Medical Association and the Carinthian Ministry of Health]. / Reevaluation von Zervixabstrichen bei Zervixkarzinompatientinnen. Regionales Qualitätssicherungsprogramm unter Mitwirkung der Osterreichischen Gesellschaft für Zytologie, der Kärntner Arztekammer und der Landessanitätsdirektion Kärntens.

BACKGROUND AND METHODS: To evaluate the reasons for the occurrence of invasive cervical cancer in Carinthia despite cytological screening, all 132 patients diagnosed with cervical cancer in the years 2000-2002 were recorded and all gynecological cytological smears made within the 5 years prior to the diagnosis of cancer were reevaluated. RESULTS: Within the 5 years prior to diagnosis, no gynaecological cytological smear was found for 50% of the patients diagnosed with cervical cancer in the years 2000-2002. In the year 2002, a total of 53 patients were reported to have cervical cancer and 78 smears were reevaluated. Of all the smears primarily diagnosed as negative, 49% were found to be positive (> or =Pap III) after reevaluation and 92% of all smears "correctly" diagnosed as negative showed quality deficiencies. The interobserver variability (kappa-statistics) showed a moderate value when the primary screening results were compared with the reevaluation. The interobserver variability within the group of reevaluators was also moderate.

Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations.

The aim of this study was to evaluate the prevalence of simple sequence variation in the BRCA2 gene. To this end, 71 breast and breast-ovarian cancer (HBC/HBOC) families along with 95 control individuals from a wide range of ethnicities were analyzed by means of denaturing high-performance liquid chromatography (DHPLC) and direct sequence analysis. In the coding (10 257 bp) and non-coding (2799 bp) sequences of BRCA2, 82 sequence variants were identified. Three different, apparently disease-associated BRCA2 mutations were found in six HBC/HBOC families (8%): two splice site mutations in introns 5 and 21, and one frameshift mutation in exon 11. In the coding region, 53 simple sequence variants were found: 35 missense mutations, one 2 bp deletion (CT) resulting in a stop at codon 3364, one nonsense mutation with a stop at codon 3326, one deletion of a complete codon (AAA) resulting in the loss of leucine, and 15 silent mutations. In the non-coding region, 26 polymorphisms were detected. Of the 79 sequence variants that were not obviously disease-associated, eight were detected only in HBC/HBOC families. The remaining 71 variants were identified in both HBC/HBOC families and control individuals. Sixty three sequence variants (80%) were specific for a continent. Forty two percent (33 out of 79) of the sequence variants were detected exclusively in Africa, though only 13% of the 332 chromosomes screened were of African origin. Our data indicate that, in BRCA2, simple sequence variation is frequent [in the coding region 1 in 194 bp (straight theta = 2.2 x 10(-4)), and in the non-coding region 1 in 108 bp (straight theta = 4.4 x 10(-4)), respectively].

BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics.

We identified 17 BRCA1 mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high-performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non-Austrian origin. In addition, 6 rare missense mutations (allele frequency < 1%) with unknown biological effects were identified. Four mutations occurred more than once in the Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty-four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty-eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age-related, node-negative control group. The prevalence of grade III tumors was marginally significant. Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age-related, node-negative comparison group, showed no statistical difference.