Comparison of different approaches for assessment of HER2 expression on protein and mRNA level: prediction of chemotherapy response in the neoadjuvant GeparTrio trial (NCT00544765).

Human epidermal growth factor receptor 2 (HER2) testing is an essential part of pathological assessment in breast cancer patients, as HER2 provides not only prognostic but also predictive information on response to targeted therapy. So far, HER2 test accuracy of immunohistochemistry/in situ-hybridization techniques is still under debate, and more reliable and robust technologies are needed. To address this issue and to evaluate the predictive value of HER2 on chemotherapy, we investigated a cohort of 278 patients from the GeparTrio trial, a prospective neoadjuvant anthracycline/taxane-based multicenter study. In the GeparTrio trial, patients were not treated with any anti-HER2 therapy, as this was not standard therapy at this time. The HER2 status was analyzed by three different approaches: local and central evaluation using immunohistochemistry combined with in situ-hybridization as well as evaluation of HER2 mRNA expression using kinetic RT-PCR from formalin-fixed, paraffin-embedded (FFPE) tissue samples using a predefined cutoff. HER2 overexpression/amplification was observed in 37.3% (91/244) and 17.9% (41/229) of the informative samples in the local and central evaluations, respectively. Positive HER2 mRNA levels were found in 19.8% (55/278). We observed a highly significant correlation between central HER2 expression and HER2 status measured by kinetic RT-PCR (r = 0.856, P < 0.0001) and an overall agreement of 95.6% (κ statistic, 0.862, CI 0.77-0.94). Further, central HER2 as well as HER2 mRNA expression were predictors for a pathological complete response after neoadjuvant anthracycline/taxane-based primary chemotherapy in a univariate binary logistic regression analysis (OR 3.29, P = 0.002; OR 2.65, P = 0.004). The predictive value could be confirmed for the central HER2 status by multivariate analysis (OR 3.04, P = 0.027). The locally assessed HER2 status was not predictive of response to chemotherapy. Our results suggest that standardized methods are preferable for evaluation of HER2 status. The kinetic RT-PCR from FFPE tissue might be an additional approach for assessment of this important prognostic and predictive parameter but has to be confirmed by other studies.

[Reversible bilateral changes in cerebral proton-spin tomography in eclampsia]. / Reversible bilaterale Veränderungen im zerebralen Kernspintomogramm bei Eklampsie.

HISTORY AND CLINICAL FINDINGS: Case 1: A 19-year-old primigravida was hospitalised in the 24th week of pregnancy after a series of grand-mal seizures. Investigation showed the classical eclamptic triad of oedema, hypertension and proteinuria. Case 2: 6 days post-partum a 24-year-old primipara developed hypertension and typical clinical prodromata. Subsequently she had a series of sometimes initially focal grand-mal seizures. TREATMENT AND COURSE: In both cases seizures ceased following pharmacological treatment. The pregnancy in the first case remained intact. Cerebral magnetic resonance imaging (MRI) demonstrated characteristic findings in both cases, in case 1 bilateral disseminated supratentorial foci of oedema without space-occupying features, in case 2 occipital white matter oedema and several supratentorial foci. All changes were completely reversible, in case 1 after 10 days, in case 2 after 16 days. CONCLUSIONS: Together with the clinical findings the focal changes on MRI provide a characteristic picture. MRI can thus be an important aid to the diagnosis of eclampsia and will prevent a misinterpretation as focal encephalitis or venous sinus thrombosis.

Allelic imbalance on chromosome 13q: evidence for the involvement of BRCA2 and RB1 in sporadic breast cancer.

Recently, the breast cancer susceptibility gene BRCA2 has been identified in chromosome 13q, a region that also contains the retinoblastoma gene RB1. To elucidate a possible role of BRCA2 and RB1 in sporadic breast tumorigenesis, allelic imbalance (AI) at 13q loci was examined in 78 primary sporadic breast tumors. AI was found in 52-63% of tumors. Nine tumors showed AI only in the BRCA2 region but not at RB1. Six tumors showed AI at RB1 but not in the BRCA2 region. AI in the BRCA2 region correlated significantly with aneuploidy (P = 0.032) and AI at RB1 with small tumor size (P = 0.025). Our data suggest that BRCA2 and RB1 may be both distinct target loci for AI on chromosome 13 in sporadic breast cancer.

[Pregnancy following organ transplantation]. / Schwangerschaften nach Organtransplantation.

In 17 of 74 patients, in the 20-40 years of age group, who had undergone an organ transplantation (kidney or liver), the course and outcome of pregnancy were evaluated. In three cases, the pregnancies ended in premature miscarriage and in five cases they were terminated for medical reasons. Nine infants were born alive between the 32nd to the 40th week of gestation, six of them spontaneously, three of them by abdominal Caesarean section. One of these infants born in the 32nd week of gestation with a birth weight of 800 grams died on the second day after birth. One infant born in the 33rd week of gestation showed incidence of a persistent ductus arteriosis Botalli. Four of the nine newborns suffered from intrauterine dystrophy. The birth weight of four further infants corresponded to the 10th to 25th percentile. Neither the incidence of a maternal varicella zoster infection in the early stages of pregnancy nor the reactivation of a herpes simplex (HSV) and cytomegalia virus infection during the pregnancy resulted in any perceptible damage to the infant or transplant. During pregnancy, three of the mothers were treated with immunosuppressants, either with a combination of azathioprine and prednisone (conventional) or cyclosporine (CSA) and prednisone, or with a combination of all three drugs (triple therapy). As opposed to the newborn of those mothers, who had been treated conventionally, the newborn of those treated with CSA showed post partum a tendency towards hypocalcaemia. Two of the mothers gave birth to their infants outside the Federal Republic of Germany.(ABSTRACT TRUNCATED AT 250 WORDS)

Thermography in the follow-up of breast cancer patients after breast-conserving treatment by tumorectomy and radiation therapy.

It is often suggested in the literature that thermography is able to diagnose a recurrence in the breast after breast-conserving therapy by a rise in breast temperature much earlier than other diagnostic tools, but no thermographic values are presented. The thermographic data of a prospective study of 309 women after breast-conserving therapy were evaluated. Seventeen of these women had an intramammary recurrence. A total of 2432 individual measured values were evaluated from 292 patients without evidence of a recurrence and 146 measured values from 17 patients with intramammary recurrence. The thermographic behavior of the breast after breast-conserving therapy is not uniform. However, the breast temperatures of the patients with intramammary recurrences were not significantly different from those without recurrences. This means that thermography is of no value in the care after breast-conserving therapy.

High-risk pregnancies and amniotic fluid isoamylase activity.

A kinetic test (Phadebas) was employed to determine the isoamylase activity in 77 amniotic fluid samples taken from a total of 60 high-risk pregnancies at different gestational ages. It was ascertained that in high-risk pregnancies the s-type isoamylase level frequently deviates from the common scatter range of the respective week of gestation. The measured activity of the s-type isoamylase is subsequently set in relation to the pre- and postnatal state of the newborn. The findings support the assumption that in addition to ultrasound, hormone determination and cardiotocography, the estimation of s-type amylase activity in amniotic fluid may serve as an index for fetal well-being. A reduced secretion of the parotid gland as a result of fetal stress is discussed as a possible cause of the ascertained enzymatic changes in the amniotic fluid.

Amniotic fluid isoamylase activity in uneventful pregnancies.

A kinetic test (Phadebas) was used to determine the isoamylase activity in 50 serum specimens and 159 samples of amniotic fluid. A highly significant difference between the isoamylase patterns of serum and amniotic fluid was ascertained which strongly supports the view that amylase activity in amniotic fluid is not of maternal origin. During the whole course of gestation the activity of pancreatic isoamylase was constantly low whereas there was an increase of nonpancreatic activity (S-type amylase) from 44 +/- 10 U/l in the 18th week of gestation to 445 +/- 170 U/l in week 39/40. A comparison between the dispersion of the ascertained values and the lecithin-sphingomyelin (L/S) ratio showed a clear overlapping. There was a correlation coefficient of r = 0.645 for 115 amniotic fluid specimens examined in our investigation. The findings show that the estimation of nonpancreatic isoamylase (S-type amylase) activity in amniotic fluid is a valuable indirect parameter for determining fetal maturity and fetal lung maturity. The easy and quick determination method will provide even those hospitals with an index of fetal maturity which are presently not in a position to estimate the L/S ratio, thus being of great assistance in the field of premature deliveries.

Intracavitary therapy with radioactive yttrium: results of animal experiments.

The distribution of radioactive yttrium was studied in guinea-pigs. The injection of 1,5 mci of radioactive yttrium leads to a mean surface dose of 20 Gy which can be obtained within 5 days. An extrapolation of these findings to the peritoneal surface of human beings should lead to a corresponding dose of 64 mci.

[The value of thermography in the diagnosis of breast cancer and in the selection of risk groups]. / Der Wert der Thermographie bei der Diagnostik des Mammakarzinoms und bei der Selektion von Risikokollektiven.

Within the framework of a prospective screening study for breast cancer, mammographic and thermographic examinations were performed in 11546 clinically asymptomatic women between 1973 and 1980. Until 1986, breast cancer was diagnosed in 141 women. Conforming with the literatur we demonstrate that the accuracy of thermography declines with decreasing tumour size (pTis 27%, pT1 33.3%, pT2 64%). The rate of breast cancer incidence in women with at least one thermogram considered suspicious or requiring further investigation was 2.7 +/- 0.4 during a period of up to 12 years. This value is not higher than that of many other risk factors and lies clearly below the factor of familial predisposition.

Premature labor contractions and the value of serum ferritin during pregnancy.

In general, the diagnosis of pregnancy-related anemia relies on the estimation of the hemoglobin level. The findings of this study suggest that the additional estimation of serum ferritin - a reliable index of the iron stores - can improve the diagnosis of anemia. Hematological data of 150 pregnant women were retrospectively related to the courses of pregnancy, in particular to the incidence of premature labor contractions. 70% of the pregnant women included in the investigation had a serum ferritin value below 20 micrograms/l and thus iron deficiency. If the hemoglobin value alone had been estimated, 50.6% of the women with iron deficiency (serum ferritin less than 20 micrograms/l) would not have been detected among those pregnant women with a hemoglobin value of more than 11 g/dl. These findings are also of particular relevance as a significant correlation has been found between the incidence of premature labor contractions and the serum ferritin level: only 11% of the pregnant women investigated whose serum ferritin values exceeded 20 micrograms/l had premature labor contractions, whereas premature labor was recorded in 48% of the pregnant women with serum ferritin values below 10 micrograms/l.

Anemia, ferritin and preterm labor.

The results of this study suggest that the additional determination of serum ferritin in pregnancy is necessary for a more reliable classification of iron deficiency. In 300 pregnant women the hematological values (Hb, MCH and serum ferritin) were determined toward the end of gestation. In 36 per cent of the women both Hb values greater than 11 g/dl and MCH values less than 28 pg fail to give evidence of an existing iron deficiency, indicated by serum ferritin values below 20 micrograms/l. The determination of serum ferritin is of particular relevance as a significant correlation was ascertained between low serum ferritin levels and the incidence of preterm labor: 52.3% of the women with serum ferritin levels below 10 micrograms/l and only 9.5% of the women with serum ferritin levels above 20 micrograms/l went into preterm labor. A convincing explanation for this has not yet been found.

[Comparison of microwave and infrared thermography in detecting malignant breast tumors]. / Vergleich von Mikrowellen- und Infrarotthermographie bei der Entdeckung von malignen Brusttumoren.

Microwave thermography is a new method in the diagnosis of breast cancer. The paper reports on the use of a microwave thermographic unit in the examination of 190 patients. Evaluation criteria are defined and the results are compared with those obtained by infrared thermography.

Treatment of advanced cancers of the cervix uteri with external irradiation alone.

The five year survival rates of 150 patients who were treated by external irradiation alone for cancers of the cervix uteri are presented. Intracavitary radium therapy had been rejected as inappropriate in all of them on account of the size and type of spread of the tumor. The average age of the selected patients was considerably higher than that of control groups. Results and incidence of side-effects are comparable with those obtained by radium-telecobalt therapy; however, rectovaginal/vesicovaginal fistulas as a reaction to radiation treatment did not occur.