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.

Familial cancer aggregation in cases of adenocarcinoma corporis uteri.

In a detailed prospective interview study, all newly diagnosed cases of adenocarcinoma corporis uteri at Malmö during a 2-year period (n = 51) were analysed with regard to the occurrence of tumors in first-degree relatives. The families of the proband's male consorts were used as controls. Sisters and mothers of probands had tumors (particularly of the corpus uteri or breast) more often than had controls. Colon and prostate cancer also figured in family histories of proband relatives, more often and with earlier age at onset than in controls. Nine patients (18%) either had additional concomitant malignancies, or had had such malignancies previously. Familial cancer predisposition was associated with poorly differentiated anaplastic cancer of the corpus uteri with poor prognosis. Three cases of familial cancer (CFS) observed at Malmö are also described, in which the probands presented with adenocarcinoma corporis uteri. The findings suggest that a hereditary, cancer predisposing factor (gene) is involved in a significant proportion of cancer corporis uteri, and that it is expressed in a heterogeneous tumor pattern, predominantly at sites sensitive to hormonal influences.

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.

[Gonorrhea infection as a risk indicator for cervix cancer]. / Die Gonorrhö-Infektion als Risikoindikator für das Kollumkarzinom.

The epidemiology of cervical cancer suggests that, like a venereal disease, it is transmitted by sexual intercourse. Out of 164 women who had gonorrhea in 1954 and 1959, preinvasive cervical cancer was diagnosed in 29 (17.7%) and invasive cervical cancer in 8 (4.9%) 23 and 24 years later respectively. Preinvasive and invasive cervical cancers were also still developing toward the end of the observation period, and for this reason the incidence of cervical cancer was investigated again in the same group of women 30 and 31 years, respectively, after the gonorrhea. Two more preinvasive and two invasive cervical cancers were diagnosed, bringing the total number of women who had had gonorrhea and subsequently had a cervical malignancy to 40 (24.4%). In the control group, of the same age and from the same urban population, cervical malignancy occurred in 9 cases (5.6%; p less than 0.001). This corresponds to a 4.4-fold relative risk in the cohort of gonorrhea patients. The fact that 25% of all women who have had gonorrhea develop a cervical malignancy indicates that a history of gonorrhea is the most unequivocal variable for predicting the subsequent development of cervical cancer. These women should be kept under closer observation; pathologic smears should be analyzed and dealt with more specifically.

Placental proteins (PP 5, PP 12 and PP 14) in ovarian tumors. A preliminary report.

Using a specific radio-immunoassay, the placental proteins PP 12, PP 14 and PP 5 were studied in serum for 2 patients with ovarian cancer and 7 with benign ovarian tumor. Elevated levels of PP 14, found in one endometroid ovarian cancer, decreased during successful treatment. PP 14 could also be found in the blood of nude mice grafted with this tumor. One patient with serous kystadenocarcinoma had a slightly elevated level of PP 14 at diagnosis, increasing as the tumor progressed. PP 14 was demonstrated histochemically in both the original tumor and the grafted. Ascitic fluid was rich in PP 14. Elevated levels of the proteins PP 12 and PP 5 were not found in these patients, however. In seven benign ovarian tumours, low PP 14 serum levels were found. The conclusion drawn from this study is that PP 14 can constitute a tumor marker in ovarian cancer.

Zinc concentrations in maternal blood during pregnancy and post partum, in cord blood and amniotic fluid.

Zinc deficiency was reported to lead to congenital malformations and abnormal fetal development, and zinc concentration in amniotic fluid has been found to be correlated with fetal birth weight. In the present study, zinc concentrations were estimated in 8 pregnant women at 15 gestational weeks and 68 pregnant women at term. Maternal serum zinc concentration in early and term pregnancy was significantly lower than that of the non-pregnant controls (mean values +/- SEM being 9.8 +/- 0.6, 9.3 +/- 0.2, and 11.5 +/- 0.3 mumol/l, respectively). Maternal serum zinc concentrations reached the non-pregnant level by one week post partum. The mean serum zinc concentration in cord blood was 14.4 (+/- 0.4) mumol/l. The zinc concentration in the amniotic fluid was very low both in early pregnancy and at term 1.1 and 0.8 mumol/l, respectively, and no correlation was found to the birth weight. Low serum zinc content in pregnant women occurs as a normal feature and congenital malformation as a consequence of disturbed zinc metabolism is probably only to be seen in instances of extreme zinc deficiency in conjunction with malnutrition.

Familial occurrence of cervical cancer, stages 0-IV.

All patients hospitalized in 1982 at the Department of Gynecology in Malmö because of malignancy of the cervix uteri attended an interview study concerning the presence of cervical cancer among their nearest relatives. In addition, these patients were questioned concerning earlier gonorrheal infection. The blood group was determined as also was the secretory status and Gm allotype. As a control group the families of the male consorts were used. Cervical cancer was found significantly more often in mothers of the patients (7.9%) than in the consorts' mothers (1.0%). Sisters, aged 20 or over, of the patients had cervical cancer significantly more often (7.5%) than sisters of the consorts (1.1%). Moreover, cervical cancer in mothers and/or sisters was found in 15.6% of the patients. In cases of invasive cancer or previously operated CIS, this figure was 17.5%. The patients did not differ significantly from the normal population regarding blood group or secretory status. A somewhat lower, although non-significant, frequency of Gm(1) allotype was found in patients with invasive cancer, compared with patients with CIS. Patients with a positive family history of cancer had more often had gonorrhea (24%) than patients with a negative family history (18%). The study indicates a multifactorial etiology for cervical cancer.

Increased frequency of carcinoma of the uterine cervix in women married to men with a previous gonorrheal infection. An epidemiological study.

An earlier investigation showed an increased frequency of squamous epithelial carcinoma of the cervix in women who had experienced gonorrhea, but that there was a long lag between the infection and diagnosis of the cervical malignancy. The present work is a retrospective study of cervical malignancy in women married to men who had had gonorrhea between 26 and 37 years previously. The women have been distributed into three groups: i) those who were married to their spouse at the time he had gonorrhea and who themselves became infected, ii) those who were married to their spouse at the time of his gonorrhea but who did not themselves become infected, iii) those who were not married to the man in question at the time of his gonorrhea and who do not recall having had had gonorrhea. The incidence rates of cervical neoplasm were found to be: group i, 27.1%, group ii, 21.7%, and group iii, 13.7%. For all three groups the figures are significantly higher than in an age-related control group drawn from the normal population. The results of the investigation lead one to suspect that a carcinogenic agent had been transferred by sexual intercourse together with the gonorrhea and that the man was the bearer of this agent long after he had undergone treatment for his gonorrhea, but that not all the women so exposed had developed a cervical neoplasm.

Growth and function of human placenta and amnion grafted to nude mice. A preliminary communication.

Normal human placenta and amnion from the 20th week of pregnancy were transplanted into nude mice. The transplants retained the histological and immunohistochemical picture of the original tissue and maintained synthesis of human chorionic gonadotropin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), GnRH and placental proteins PP5, PP11 and PP12 for 5 weeks. This experimental model has a wide potential application for studies on placental protein synthesis and the hormonal influence of human placenta on other simultaneously transplanted human tissues.

HSV 2-associated antigens in human cervical tissues before and after grafting in nude mice.

Biopsy material from human invasive cervical carcinoma, carcinoma in situ (CIS) and normal uterine cervix was transplanted into nude mice, some of which were then injected with estrogen or progesterone during a follow-up of 1-4 weeks. The cervical cells were analysed prior to and after passage in nude mice by the anticomplement immunofluorescence (ACIF) assay for the presence of herpes virus associated antigens. Such antigens were found in a few cells in three out of seven transplanted cervical cancers prior to the grafting and in one out of 3 cases with normal tissue. After the grafting period HSV-related antigen was found in 6 out of 7 cases of cervical cancer in grafting material from estrogen-stimulated mice. Without hormonal stimulation, 5 out of 7 showed a positive reaction. Hence the expression of the HSV-related antigen seemed enhanced after grafting in nude mice.

Gonorrheal infection followed by an increased frequency of cervical carcinoma.

In a town with a fairly centralized health service and a well organized gynecologic health control, women who had had gonorrhea in 1954 or 1955 were reviewed for presence of cervical neoplasia and compared with age-matched controls. Of 164 women studied, 29 (17.7 per cent) had 24 or 23 years later developed cancer in situ, compared with 7 (4.3 per cent) of the controls (p < 0.001), while 8 (4.3 per cent) had invasive cancer colli uteri against only one (0.6 per cent) of the controls (p < 0.02). Malignant disease of the portio proved at least four times as common among the women with gonorrhea in their history as among the controls. The findings corroborate the view that cervical carcinoma is a sexually transmitted disease. It may be assumed that at least every fourth woman who had had gonorrhea had been or is a carrier of the carcinogenic agent(s). It is probably easier to search for and detect such agents in association with gonorrhea than in patients with already manifest cancer of the uterine cervix.