Prognostic impact of chromosome aberrations in ovarian cancer.

Clinico-cytogenetic correlations were assessed in 88 patients with malignant ovarian tumours. Cytogenetic analysis of the primary tumours yielded normal karyotype (N) in 33 patients and abnormal karyotypes (A) in 55 patients. Within the A group, seven tumours had simple abnormalities (AS), i.e., numerical changes only or a single structural aberration, and 48 had karyotypes with complex aberrations (AC). A correlation analysis between groups N and A revealed that cytogenetic abnormalities were more often found among seropapillary tumours, and that cases with abnormal karyotypes on average were of higher stage and more often had residual tumour mass after initial surgery (P less than 0.05 for all variables). When the three groups N, AS, and AC were compared, they were found to be significantly different with regard not only to the three parameters mentioned above, but now tumour grade also appeared to correlate with karyotypic pattern (P = 0.001), with poorly differentiated tumours having the most complex karyotypes. In a correlation analysis between karyotypic pattern and survival, group A patients had shorter survival than group N (P = 0.049). In the corresponding analysis between groups N, AS, and AC, the differences were also significant (P = 0.039), with shorter survival in group AC than in groups N and AS. Stage, grade, residual tumour after primary surgery, and performance status also correlated with survival time. A multivariate analysis identified abnormal karyotype as being independently associated with short survival in advanced clinical stages (P = 0.030) of ovarian carcinoma. We conclude that cytogenetic analysis of tumour cells may be of clinical value in the assessment of prognosis in patients with malignant ovarian tumours.

Chromosome aberrations in 35 primary ovarian carcinomas.

Cytogenetic analysis was performed on short-term cultures of primary ovarian carcinomas from 62 patients. Cytogenetic analysis was successful in 59 cases. Clonal chromosome aberrations were detected in 35 tumors. Only numerical changes or a single structural change were found in five carcinomas: trisomy 12 was the sole anomaly in two tumors, one tumor had the karyotype 50,XX, + 5, + 7, + 12, + 14, a fourth tumor had a balanced t(1;5), and the fifth tumor had an unbalanced t(8;15). The fact that four of these five carcinomas were well differentiated suggests that simple karyotypic changes are generally characteristic of these less aggressive ovarian tumors. The majority of the cytogenetically abnormal tumors (n = 30) had complex karyotypes, with both numerical and structural aberrations and often hypodiploid or near-triploid stemlines. The numerical imbalances (comparison with the nearest euploid number) were mostly losses, in order of decreasing frequency -17, -22, -13, -8, -X, and -14. The structural aberrations were mostly deletions and unbalanced translocations. Recurrent loss of genetic material affected chromosome arms 1p, 3p, 6q, and 11p. The breakpoints of the clonal structural abnormalities clustered to several chromosome bands and segments: 19p13, 11p13-15, 1q21-23, 1p36, 19q13, 3p12-13, and 6q21-23. The most consistent change (16 tumors) was a 19p + marker, and in 12 of the tumors the 19p + markers looked alike.

Bilateral ovarian carcinoma: cytogenetic evidence of unicentric origin.

Cytogenetic analyses were performed on the tumors from both ovaries in 15 patients with bilateral ovarian carcinoma. In 4 of them, omental implants were also examined. Abnormal karyotypes were detected in 11 cases. The baseline karyotypes in the 2 tumorous ovaries were identical in each patient, indicating that bilateral ovarian cancer develops by metastatic spreading. There was no clear-cut evidence of differences in the clonal evolution between the tumors of the 2 ovaries, and hence the side harboring the primary tumor could never be determined. The metastatic nature of the omental implants was proved by the fact that their karyotypes were indistinguishable from those of the ovarian tumor tissue.

Trisomy 12 is a consistent chromosomal aberration in benign ovarian tumors.

Clonal karyotypic abnormalities were detected in 7 of 42 cytogenetically analyzed benign ovarian tumors. An adenofibroma had -X and a mucinous cystadenoma had t(1;11)(q25;q23) as the sole abnormality. Trisomy 12 was found in the remaining five tumors. It was the only change in two fibromas and a serous cystadenoma; the fourth tumor, a mucinous cystadenoma, had one clone with +12 and one with +12 and +10, and the fifth tumor, a fibrothecoma, had +4,+9,+12. The finding of trisomy 12 in five of seven karyotypically aberrant tumors suggests that this aberration characterizes a hitherto unrecognized cytogenetic subgroup of benign ovarian neoplasms.

Consistent occurrence of a 19p+ marker chromosome and loss of 11p material in ovarian seropapillary cystadenocarcinomas.

Cytogenetic analysis of short-term cultures from 11 moderately to poorly differentiated ovarian seropapillary cystadenocarcinomas revealed clonal chromosomal abnormalities in nine tumors. Two bands were involved in structural rearrangements in more than half of the tumors. The band most frequently affected was 19p13; rearrangements giving rise to a 19p+ marker chromosome were found in seven tumors, and in four of them the 19p+ markers appeared to be identical. Structural rearrangements resulting in loss of 11p13-11pter material were found in six tumors.

A study of cryosurgery for dysplasia and carcinoma in situ of the uterine cervix.

We studied 22 patients with a histopathological diagnosis of severe dysplasia and 89 patients with a diagnosis of carcinoma in situ of the uterine cervix. Twenty patients (18 per cent) had negative cervical smears for four to six years after diagnosis by biopsy of the cervix. The 91 patients with persistently abnormal smears were treated by cryosurgery, using a double freeze technique with nitrous oxide. Seventy-four (86 per cent) had persistently normal cervical smears after one treatment and eight after a second treatment while nine patients required conization for recurrently abnormal cervical smears. The duration of follow-up was five or six years in 48 patients (53 per cent). In a subsidiary study, material was obtained for histological examination from 72 patients with normal smears by endocervical curettage and multiple biopsies of the cervix; 8 showed slight atypia and 2 had residual carcinoma in situ.

Date of confinement prediction from serum diamine oxidase determination in early pregnancy.

A reliable assessment of the date of confinement is often important in early pregnancy. In many pregnancies the menstrual history is in doubt or the size of the uterus does not correspond to the last menstrual period. During early pregnancy the rise of serum diamine oxidase (DAO) is confined within narrow limits to certain weeks of gestation. In a series of 189 patients from the 6th to 16th week of pregnancy, the date of confinement was estimated by enzyme determination, and was also calculated by Naegel's formula. Dating by serum DAO was found to be more accurate than the menstrual history, and this technique is recommended for use in routine clinical practice.