An assessment of the use of interphase FISH with chromosome specific probes as an alternative to cytogenetics in prenatal diagnosis.

We have assessed the effects that would have been observed if we had changed from standard prenatal diagnosis to interphase fluorescence in situ hybridization (FISH) on our amniocentesis samples. We aimed to estimate the number of cases with aberrations other than chromosomes 13, 18, 21, X and Y, which would not have been detectable by FISH and to assess the potential clinical implications for these cases. In 1687 prenatal diagnoses, 111 cases had abnormal cytogenetic reports (6.5% aneuploidy rate). Out of those 111 cases, 14 had chromosomal abnormalities not detectable by FISH but four of these had major structural abnormalities diagnosed on ultrasound, which would have lead to counselling of a very poor prognosis anyway. In 10 cases without abnormal ultrasound findings, if FISH had been used rather than cytogenetics, it appears that there may have had no detrimental effects on the clinical outcomes of the cases studied. Out of those 10 cases, two pregnancies were terminated because of abnormal cytogenetic results (one was due to maternal age and the second one was due to abnormal biochemical screening) (mosaic 46,XY, /47,XY,+mar and 46,X,del(8)(p21) respectively) and their post-mortem results also did not show any abnormalities. One pregnancy was continued in spite of a de novo chromosomal rearrangement and resulted in an apparently normal live birth. Five cases (including a set of twins) with inherited balanced translocations resulted in four normal live births and one unexplained intrauterine death at 32 weeks' gestation and post-mortem was declined. One case with a paternally derived abnormal chromosome 21, decided to continue the pregnancy and resulted in a normal live birth. The last case in this group resulted in a rhesus related intrauterine death in the second trimester, and although an abnormal chromosome 13 insertion (paternally derived known aberration) there was no abnormality found at post-mortem. Therefore, we suggest that it is reasonable to use FISH as an alternative prenatal diagnosis for indications such as advanced maternal age and abnormal maternal serum biochemical screening when high quality ultrasound scanning is performed, but FISH should only be used as an additional test to conventional cytogenetics for the other indications, especially when abnormalities are found on ultrasound scan.

Antenatal invasive therapy.

The value of fetal therapy relates to the balance of benefit versus risk taking into account alternatives such as post-natal therapy. Since this balance is also determined by the natural history and prognosis of a given condition, the fact that any condition diagnosed pre-natally has a worse prognosis than the same condition diagnosed post-natally will be described. On this basis we classify the interventions into those that are clearly of benefit in the right cases, those that are possible now but are still being assessed and other experimental ideas.

Molecular cytogenetic analysis of five newly established cervical cancer cell lines using G banding and fluorescence in situ hybridization.

Cervical tumors nearly all have complex karyotypes and more precise cytogenetic information is required to establish whether specific rearrangements occur, and if they are related to the type of HPV infection found. The karyotypes of five recently established cervical cancer cell lines, three from squamous cell carcinomas (two HPV 16 +ve and one HPV 18 +ve), one from an adenocarcinoma (HPV -ve), and one from an adenosquamous carcinoma (HPV 16 +ve), have been analysed using fluorescence in situ hybridization (FISH), with 23 chromosome specific paints, YACs and cosmids as probes, in addition to conventional G banding, in order to identify markers and clarify the breakpoints. Chromosomes 1 and 3 were rearranged in all cell lines. Breakpoints in the squamous lines were all in 3q. but in different regions. Small metacentrics involving chromosome 5 were a del(5q) in one line, and a t(X;5) in another, rather than i(5p). The region 6q21 was involved in three cases and chromosome 9 was rearranged in four. An i(8q) was found in three squamous carcinoma cell lines. Structural changes of 11q were found only in two cases, but a marker 11 representing amplification in the 11q14-22 region was duplicated in the adenosquamous line.