[Amplification and expression of c-erbB2 oncogene in normal, hyperplastic, and malignant endometria].

OBJECTIVE: To study the correlation of development and survival with amplification of c-erbB2 oncogene in endometrial carcinoma. METHODS: The amplification and expression of c-erbB2 oncogene were determined from formalin-fixed, paraffin-embedded tissues of 25 normal, 31 hyperplastic, and 72 malignant samples of the endometrium in 128 patients, using differential polymerase chain reaction (DPCR) and an immunohistochemical technique. RESULTS: Amplified c-erbB2 (2 to 12 copies) were found in two of 25 (8.0%) normal, 15 of 31 (48.4%) hyperplastic, and 45 of 72 (62.5%) malignant samples. When the results of DPCR were compared with those of the immunohistochemical method, the negative findings concide well with one another, i.e., nonamplification was associated with the absence of immunoreactivity. It was noted that the amplified c-erbB2 was found more significantly in complex and a typical hyperplasias than in simple hyperplasias. The high-level c-erbB2 amplification (at least five copies) was significantly correlated with the histological grade of endometrial carcinoma and vascular or lymphatic invasion. No correlation was seen between c-erbB2 amplification and overall survival in the present group of patients. CONCLUSIONS: The amplified c-erbB2 may play a potential role in the early development of some endometrial carcinomas. The high-level c-erbB2 amplification may identify a subset of aggressive endometrial carcinoma that involves vascular or lymphatic invasiveness and poor cell differentiation playing the role of a marker for clinical prognosis.

Human papillomavirus detection of endometrioid carcinoma with squamous differentiation of the uterine corpus.

Many studies have shown a link between human papillomavirus (HPV) and cervical carcinoma. However, studies on the association of HPV with endometrioid carcinoma of the corpus uteri are sparse and controversial. In this study, 33 formalin-fixed, paraffin-embedded tissue samples of endometrioid carcinoma with squamous cell differentiation in grade 1 (adenoacanthoma) and 10 additional samples of endometrioid carcinoma with less squamous cell differentiation in grade 2 or 3 (adenosquamous carcinoma) were examined by the hybrid capture system for the presence of the 14 most common anogenital HPV types, consisting of low-risk HPV types 6, 11, 42, 43, and 44, and intermediate- and high-risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56. No evidence of high-risk HPV DNA types was found in any of these samples. The low- risk HPV DNA types were found in three samples and showed borderline results (+/-) in 6 samples by the hybrid capture system. The 43 samples were tested by dot blot hybridization with HPV probes 6/11, 16/18, and 31/33/35. Only 1 sample was positive for HPV 6/11. The results of this study did not indicate an association between HPV infection and endometrioid carcinoma with squamous cells, though the endometrial mucosa of the corpus uteri is anatomically connected to the endocervical epithelium, and in some cases HPV has been postulated to possibly cause squamous cell differentiation of the endometrium. Our findings are in accord with the concept that HPV infection leading to malignancy is highly site- and tissue-specific. In conclusion, the endometrium may not be a suitable host epithelium for HPV replication and maturation.

Human papilloma virus DNA: a factor in the pathogenesis of mammary Paget's disease?

The paraffin sections from 20 nipples with Paget's disease (10 central intraductal and 10 invasive ductal carcinomas) were analyzed for human papilloma virus (HPV) DNA of the low- and intermediate/high-risk groups. Polymerase chain reaction (PCR) and dot (slot) blot hybridization were used for the detection of HPV DNA types 6/11/16/18/31/33/35. In addition, we examined the c-erbB-2 oncogene expression in the specimens to differentiate benign cells in the surface epithelium of the nipple and areola from Paget cells. We found that the oncogene expression of the c-erbB-2 displayed a strong signal in the Paget cells. Using PCR and dot (slot) blot hybridization, we could not detect the HPV DNAs that are specific for the low- and intermediate/high risk-groups in the 20 cases of Paget's disease. Our results showed for the first time that this type of virus did not contribute to the pathogenesis of Paget's disease.

Amplification and expression of the c-erbB-2 oncogene in normal, hyperplastic, and malignant endometria.

Using differential polymerase chain reaction (DPCR), dot blot hybridization, and an immunohistochemical technique, we determined the amplification and expression of the c-erbB-2 oncogene in 25 normal, 31 hyperplastic, and 72 malignant samples of the endometrium in 128 patients. Using DPCR, we found amplified c-erbB-2 (two to 12 copies) in two of 25 (8%) normal, 15 of 31 (48%) hyperplastic, and 45 of 72 (63%) malignant samples. These results were closely correlated with those from dot blot (r = 0.78). When comparing the results of DPCR with those of the immunohistochemical method, we noted that the negative findings coincided with one another, i.e., nonamplification was associated with the absence of immunoreactivity. Further analysis showed that amplified c-erbB-2 was found significantly more in complex and atypical hyperplasias versus simple hyperplasias. This indicates that c-erbB-2 may play a potential role in the early development of some endometrial carcinomas. Although no correlation was seen between c-erbB-2 amplification and overall survival in our patients, high-level c-erbB-2 amplification (at least five copies) was significantly associated with the histological grade of endometrial carcinoma and vascular or lymphatic invasion. It is possible that high-level c-erbB-2 amplification identifies a subset of aggressive endometrial carcinoma that involves vascular or lymphatic invasiveness and poor cell differentiation.

Salpingitis caused by Chlamydia trachomatis and its significance for infertility.

Between July and November 1991, 32 women (mean age 24.8 years) were examined laparoscopically in our department for suspected tubal sterility. All women had smears taken from cervix, vagina, and urethra, and all were negative regarding an infection with Chlamydia trachomatis. All women had open fallopian tubes, however, with inflammatory changes that varied in degree. Fifteen women reported pains and were classified as PID (pelvis inflammatory disease)-positive, as compared to the PID-negative group of 17 women without pain. In the group of the 15 PID-positive women, we could detect Chlamydia trachomatis in the form of salpingitis in 11 cases in the direct demonstration of the infectious agent. IgA antibodies were detected in the serum of all of these women, in 12 of them IgA + IgG antibodies. In the group of the 17 PID-negative women, three were positive in the direct detection of the infectious agent, and IgA and/or IgG antibodies were detected in five cases. 38% of the women in the PID-positive group and 68% in the PID-negative group conceived within a period of one year after having completed a treatment with antibiotics.

[Measuring cesium 137 concentrations in surgical specimen of gynecologic tumors and breast milk, amniotic fluid and in umbilical cords, 6 years after Chernobyl]. / Messungen der Caesium 137-Konzentrationen in Operationspräparaten gynäkologischer Tumoren sowie in Muttermilch, Fruchtwasser und in Nabelschnüren, 6 Jahre nach Tschernobyl.

In the present study, the cesium 137 content in various human tissues was examined 6 years after the Chernobyl reactor catastrophe. The measurements were performed with a gamma-ray spectrometer by means of a germanium/lithium detector. The median of cesium 137 was 20 mBq/ml in mother's milk, 60 mBq/ml in amniotic fluid, 105 mBq/g in umbilical cords, 51 mBq/g in ovarian tumours, and 140 mBq/g in mammary carcinomas. These values lay far below the permissible limit values of 528 mBq/ml or 528 mBq/g for persons not exposed to radiation. The problems of determining the upper limit were also discussed, and it was ascertained that despite the favorably low values recorded in this study a residual risk to health cannot be absolutely precluded in the light of present-day knowledge.

C1-esterase inhibitor in uncomplicated pregnancy and mild and moderate preeclampsia.

Routine coagulation tests and measurement of the plasma levels of C1-esterase inhibitor (C1-INH) and antithrombin III were performed in 17 women with mild preeclampsia, 10 women with moderate preeclampsia and 20 women with uncomplicated pregnancy. All pregnant probands were within the third trimester of pregnancy. 20 non-pregnant women were used as controls. The groups were matched in age and the pregnant ones were also matched in gestational age. C1-INH activity and antigen were significantly reduced (p less than 0.002) in normally pregnant women as compared with non-pregnant ones. Further, C1-INH activity was lower in women with mild preeclampsia and significantly lower in women with moderate preeclampsia (p less than 0.05) as compared with normally pregnant women. None of the plasmatic coagulation tests was indicative of a consumption reaction. We conclude that C1-INH activity and antigen reductions are commonly associated with pregnancy. Furthermore, as markedly lower values can be found in mild and moderate preeclampsia, measurement of the C1-INH activity in pregnant women within the third trimester might proof useful to establish the diagnosis of a preeclamptic condition.

[Changes in antithrombin III values during and after extracorporeal circulation in heart surgery, measured on the day of operation using a chromogenic substrate and a laser nephelometer]. / Die Anderung der Antithrombin-III-Werte während und nach extrakorporaler Zirkulation in der Herzchirurgie, gemessen am Operationstag mit einem chromogenen Substrat und einem Laser-Nephelometer.

The changes in antithrombin III in 31 patients who underwent open-heart surgery were measured during the period of extracorporeal circulation and afterwards over a total period of 24 hours by means of a chromogenic substrate, as well as by laser nephelometry. Both the actual changes in antithrombin III, as well as the theoretical changes calculated by eliminating the effect of haemodilution are discussed. The functional test indicates that the loss of antithrombin-III activity, in general, is due to the effect of haemodilution. However, marked individual differences were noted in the reaction pattern. The results of nephelometric measurements were inconsistent and seemed to indicate that routine procedures in laser nephelometry are hardly suitable for the purpose of comparison of samples with marked haematocrit differences.