Biomedical subjects

G Bastert

Publications and source records attributed to G Bastert.

At least 55 records · Page 3Linked to original sources

PubMed1999

Evaluating GA733-2 mRNA as a marker for the detection of micrometastatic breast cancer in peripheral blood and bone marrow.

The GA733-2 gene encodes the epithelial glycoprotein 40, a homophilic cell-cell adhesion molecule, which is expressed on the surface of epithelial cells and associated with a variety of carcinomas, e.g. breast, colorectal and lung carcinomas. To test if it could serve as a tumor marker, we have analysed the expression of GA733-2 in bone marrow (BM) and peripheral blood (PB) from healthy donors, and of patients with haematological malignancies or breast cancer using reverse transcriptase-polymerase chain reaction (RT-PCR). The GA733-2 nested PCR was positive in 100% (8/8) of BM and 40% (16/40) of PB from healthy donors, in 100% (33/33) of BM from patients with breast cancer who had no evidence of distant metastases and also in BM and PB from patients with haematological malignancies. GA733-2 mRNA is not specific as a marker for the detection of breast cancer cells in BM and PB.

Amino Acid Sequence↗

PubMed1999

Analysis of sensitivity and specificity of cytokeratin 19 reverse transcriptase/polymerase chain reaction for detection of occult breast cancer in bone marrow and leukapheresis products.

PURPOSE: The work aimed to evaluate the sensitivity and specificity of the cytokeratin (CK) 19 reverse transcriptase/polymerase chain reaction (RT-PCR) for the detection of occult breast cancer in bone marrow and leukapheresis products. MATERIALS AND METHODS: Peripheral blood and bone marrow samples, obtained from 96 and 8 healthy donors respectively, served as negative controls. A total of 115 bone marrow samples and 29 leukapheresis samples from routine patients with breast cancer were analysed by CK19 RT-PCR. The PCR results were compared with those from routine immunocytology for CK8, 18, 19. RESULTS: The CK19 RT-PCR technique with primer pairs from Datta et al. (J Clin Oncol 12: 475-482, 1994), using an annealing temperature of 72 degrees C, allowed the detection of one tumour cell in 10(7) mononuclear cells. None of the control samples (96 peripheral blood and 8 bone marrow) that were positive for beta2-microglobulin by RT-PCR showed a signal for CK19. However, expression of CK19 mRNA was observed in 40.87% (70/115) of bone marrow and in 24.13% (7/29) of leukapheresis samples of patients with breast cancer. Standard immunocytology and PCR were combined for the detection of tumour cells. Five of the 65 bone marrow samples were found to be positive by CK19 RT-PCR, but were negative with the immunocytology method. CONCLUSION: RT-PCR using CK19-specific primers and optimal experimental conditions is a reliable and specific method for the detection of micrometastatic breast cancer cells.

Bone Marrow Neoplasms↗

PubMed1999

Evaluation of the reverse transcriptase/polymerase chain reaction for carcinoembryonic antigen for the detection of breast cancer dissemination in bone marrow and peripheral blood.

This study evaluated the specificity and sensitivity of the reverse transcriptase/polymerase chain reaction (RT-PCR) for carcinoembryonic antigen (CEA) for identification of breast tumour cells in bone marrow and in peripheral blood. Using one primer set from the A2/B3 domains of CEA with five to seven mismatches to other CEA-family members allowed reproducible detection of 1 colon tumour cell and 10 breast tumour cells in 10(7) mononuclear cells. Bone marrow samples from 181 patients with breast cancer were analysed by CEA-RT-PCR; 50 of these samples were analysed in parallel by routine immunocytochemistry. CEA-mRNA-positive bone marrow cells were found in 27.6% of the patients (50/181) with breast cancer. Five immunocytochemistry-positive samples were negative when analysed by CEA-RT-PCR. Limiting factors in the detection of micrometastatic breast tumour cells by CEA-RT-PCR are the heterogeneity of the tumour cells and the deficient expression of CEA in some of these cells. However, CEA-RT-PCR using the specific primer could detect 1 colon tumour cell in 1 x 10(7) normal peripheral blood mononuclear cells.

Bone Marrow↗

PubMed1999

Reduction of aseptic measures in gynecologic endoscopy: a comparative clinical trial.

OBJECTIVE: A prospective comparative clinical study was conducted on 200 patients to evaluate the consequences of minimizing the following standard hygienic measures in gynecologic laparoscopy: surgical scrub, patient draping, surgical gowns. STUDY DESIGN: A group of 100 patients treated according to maximum hygienic protocol was compared to a group of 100 patients undergoing laparoscopic procedures with only limited aseptic precautions. Clinical control parameters were perioperative temperature and white blood cell count up to the 4th postoperative day. Furthermore, patients and their gynecologists were interviewed 2-4 weeks after surgery to rule out any delayed manifestation of an infection. RESULTS: Perioperative infection was low in both groups. CONCLUSION: As we found no significant difference between the two collectives' control parameters, we conclude that a reduction in perioperative hygiene seems feasible for certain laparoscopic procedures. However, a larger collective should be studied in order to confirm this action.

Adult↗

PubMed1999

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer.

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12,000 mg m(-2)), carboplatin (900 mg m(-2)) and epirubicin (180 mg m(-2)). Patients were autografted with a median number of 3.7 x 10(6) CD34+ cells kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours.

Adult↗

PubMed1999

Does the measurement of four fetal arteries provide more information than the measurement of just two arteries in prenatal Doppler sonography?

OBJECTIVE: The objective of this study was to evaluate whether the measurement of two or more fetal arteries provides more information and leads to a selection of fetuses at higher risk. DESIGN: In 244 pregnancies Doppler examinations in four fetal arteries (fetal aorta, common carotid artery, middle cerebral artery, umbilical artery) were performed. The evaluation of the results was made by means of a Doppler score for standardization and systematization. The results were divided into four groups (normal, pre-pathological, pathological, highly pathological) and the individual correlations with fetal outcome parameters were investigated. The results from measuring only two fetal arteries (the fetal aorta and middle cerebral artery) were then compared with those from all four arteries. RESULTS: Increasing pathology of the Doppler score correlated with fetal outcome parameters. The results showed that if the Doppler result in the two-vessel measurement was normal (n = 180), pre-pathological (n = 29) or highly pathological (n = 12) then measuring four vessels generally brought no additional information. However, the four-vessel measurement was of advantage in the pathological group (n = 23) because it selected the high-risk fetuses (30.4%), as categorized by outcome. CONCLUSIONS: Differentiating between several degrees of pathology is important for the estimation of fetal risk. In cases of pathological Doppler findings, the measurement of more than two vessels is important in order to select fetuses at increased risk.

Arteries↗

PubMed1999

Serum bone sialoprotein in patients with primary breast cancer is a prognostic marker for subsequent bone metastasis.

Bone sialoprotein (BSP) is a noncoflagenous bone matrix protein that is important for both mineralization and cell-cell interactions. Tissue studies in primary breast cancers have shown that immunohistochemical expression of BSP is associated with a high incidence of bone metastases in the course of the disease. We used a RIA to investigate the importance of serum BSP as a marker for subsequent bone metastases. Between 1994 and 1996, preoperative blood samples were collected from 388 consecutive patients with nonmetastatic breast cancer and from 30 control patients with benign breast disease. Serum BSP concentrations were measured in a blinded fashion by RIA. The cutoff for elevated serum BSP values was 24 ng/ml, ie., two SDs above the normal mean value. Serum BSP was correlated with the risk of metastasis and analyzed with regard to its prognostic value. After a median follow-up period of only 20 months, 28 patients had developed metastases. Fourteen patients had bone metastases only, 9 visceral metastases only, and 5 a combination of osseous and visceral metastases. Of the 19 women with skeletal metastases, 17 had preoperative serum BSP values in excess of 24 ng/ml (median BSP values: 48.3 ng/ml for isolated metastatic bone disease, 30.6 ng/ml for combined metastases), whereas none of the women with visceral metastases only had elevated serum BSP concentrations (median BSP value: 12.3 ng/ml). The median serum BSP value in the control group (benign breast disease) was 8.8 ng/ml serum BSP; levels correlated with the size of the primary tumor, but not with any other prognostic factors. Using a multivariate regression analysis, serum BSP was found to be the most important independent prognostic factor for the development of skeletal metastasis (P < 0.001; relative risk, 94); its specificity was 96.7%, and its sensitivity was 89.5%. Our study shows that patients with preoperatively elevated serum BSP levels are at high risk of subsequent bone metastases in the first years after primary surgery. The mechanism of BSP in the pathogenesis of skeletal metastases is unclear. Because BSP contains an integrin recognition sequence, its expression in tumor cells may facilitate their adhesion to the bone surface. However, it is possible that a proportion of circulation BSP is derived from normal or tumor-induced bone turnover. Breast cancer patients with elevated serum BSP levels may benefit from osteoprotective adjuvant therapy with bisphosphonates.

Adult↗

PubMed1999

[Significance of the renin-angiotensin-aldosterone system for pathogenesis and early diagnosis of pregnancy-induced hypertension with special reference to mineralocorticoid receptors].

OBJECTIVE: In women with pregnancy-induced hypertension (PIH) the density of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) is reduced compared with healthy pregnant women. The same applies to plasma levels of aldosterone and 18-hydroxycorticosterone. In this study, we investigated whether alterations of these parameters preceded the development of clinical symptoms and, therefore, might be potential predictors of PIH involved in the pathogenesis. PATIENTS AND METHODS: In eighty-four women belonging to the risk-group for PIH but not showing any symptoms neither of PIH nor preeclampsia (PE) we characterized prospectively before the onset of disease in the second trimester of pregnancy mineralocorticoid receptor status in HML and steroid plasma levels of aldosterone and its precursors as well as cortisol through radioimmunoassay. RESULTS: 15 women developed PIH, three of which developed PE. Neither in the density of MR nor in the affinity the women that developed PIH showed any difference from healthy women. Steroid plasma levels were identical as well. CONCLUSION: We conclude that a reduction of mineralocorticoid receptors does not precede PIH within the peripheral blood. But still one can assume that the RAAS may be involved in the pathogenesis of PIH, possibly on a local level within the placenta or as a secondary change, initiated by still unknown factors.

Adult↗

PubMed1999

[Doppler ultrasound findings in therapy with urapidil].

OBJECTIVE: In a prospective study we investigated, whether changes in fetal or maternal circulation can be found by Doppler sonography under therapy with urapidil. PATIENTS AND METHODS: We investigated in 11 patients with severe pregnancy-induced hypertension (PIH) or superimposed preeclampsia in the third trimester. Doppler flow results of maternal and fetal vessels before and during therapy with urapidil. Hemodynamic parameters, like maternal blood pressure, and heart rate as well as other clinical parameters were assessed. RESULTS: Whereas the antihypertensive effects in the systolic and diastolic blood pressure were significant, we couldn't find changes in the resistance indices of fetal circulation. In contrast we found a decrease in the resistance indices in maternal vessels after an average of six days of urapidil therapy. These changes were significant in the uterine artery on the side of placental insertion. CONCLUSIONS: Because of only few side effects and a safe lowering of blood pressure, therapy with urapidil seems preferable to other well known drugs. Although Doppler flow velocimetry of uteroplacental vessels has no diagnostic benefit in monitoring PIH, the findings with this method under prolonged antihypertensive therapy are a chance for a better understanding of hemodynamic changes. The decrease in the resistance indices is another argument for the use of urapidil.

Adult↗

PubMed1999

[Current aspects of antihypertensive therapy in pregnant patients with pre-eclampsia].

Preeclampsia is a disease which occurs in Europe in about 6-8%, in the USA in about 7-10% and in Africa in about 18% of all pregnancies. A causal treatment of preeclampsia is, with the exception of delivery, not possible up to now. Since a prematurely delivery of the newborn has to be avoided because of the risks caused by immaturity of lungs, treatment and care of pregnant women having preeclampsia or any other kind of hypertensive diseases is restricted to the following approaches: antihypertensive treatment, volume expansion, and eclampsia prophylaxis with magnesium sulfate. Object of this treatment is to avoid complications on the mother's side caused by the disease and to postpone delivery, as far as possible from the child's side, in order to reduce the consequences of premature birth. During antihypertensive treatment of patients with serious hypertension, i.e. with diastolic blood pressure of 110 x mm Hg and higher, dihydralazine is in clinical use since 40 years, although many patients suffer from side-effects of dihydralazine such as distinctive tachycardia, headaches, fluid retention and nausea. With urapidil a well controllable antihypertensive is available, which prevents the effect of catecholamines at the vascular wall by a postsynaptic alpha-1 receptor blockade. Previous studies related to the application of urapidil in the treatment of hypertension during pregnancy certify the good controllability of urapidil following intravenous application as well as minor side-effects after start of treatment.

Antihypertensive Agents↗

PubMed1998

Reduction in new metastases in breast cancer with adjuvant clodronate treatment.

BACKGROUND: Bisphosphonates are effective against the increased bone resorption caused by certain diseases because they inhibit the activity of osteoclasts. In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the frequency of skeletal complications. Experiments in animals and preliminary clinical observations indicate that early clodronate therapy reduces the incidence of new bony metastases in breast cancer. We investigated the effects of clodronate on the incidence and extent of new metastases in patients with breast cancer. METHODS: Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone marrow (the presence of which is a risk factor for the development of distant metastases) were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients). The median length of observation was 36 months. All patients in both groups received standard surgical treatment and customary hormonal therapy or chemotherapy. RESULTS: Distant metastases were detected in 21 patients in the clodronate group and in 42 patients in the control group (P<0.001). The incidence of both osseous and visceral metastases was significantly lower in the clodronate group than in the control group (P=0.003 for both osseous and visceral metastases). Six patients in the clodronate group died, as did 22 in the control group (P=0.001). The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3.1 vs. 6.3). CONCLUSIONS: Clodronate can reduce the incidence and number of new bony and visceral metastases in women with breast cancer who are at high risk for distant metastases.

Adult↗

PubMed1998

Telomerase activity correlates with tumor aggressiveness and reflects therapy effect in breast cancer.

Telomerase appears to be an important factor for the control of cellular proliferation capacity and for tumorigenesis. Enzyme activity is highly increased in almost all human tumors and distinguishes them from benign lesions. Besides its diagnostic value, telomerase activity appears to be associated with tumor progression. The purpose of our study was to evaluate the significance of telomerase activity as a clinical marker in breast cancer. Twenty-five tumor samples from breast cancer patients were analyzed retrospectively for telomerase activity in chemotherapy-treated and untreated tumors. For each patient an identical number of cells was measured quantitatively for telomerase activity using the Telomerase-PCR-ELISA based on the TRAP (telomerase repeat amplification protocol) method. The findings were compared to clinical course, therapy and staging parameters. Telomerase activity was detected in all breast cancers. A significant correlation was found between enzyme activity and tumor size, lymph node status and stage: with ongoing tumor progression, telomerase activity appeared to increase in primary carcinomas. No correlation was seen between enzyme activity and the clinical course of patients. Without exception, telomerase activity was strongly decreased in all chemotherapy-treated tumors compared to untreated tumors. Our preliminary data indicate that telomerase activity is associated with aggressiveness of breast tumors and appears to mirror the anti-proliferative effects of chemotherapy.

Adult↗

PubMed1998

Results of iliac crest biopsies taken from 1465 patients with primary breast cancer.

This study was performed to analyze the relevance of iliac crest biopsy in patients with primary breast cancer with regard to metastases of the primary tumor and osteogenic disease. We performed intraoperative bilateral biopsy of the anterior iliac crests in 1465 patients with primary breast cancer. The bone specimens were histologically evaluated with regard to quality of the biopsy, tumor involvement, and osteogenic and hematogenic disease. Accurate and clear evaluation of the iliac crest biopsies was possible in 1365 patients (93%). Osteopenia was diagnosed in 48 patients (3.5%); 24 patients (1.7%) showed histological evidence of tumor involvement of the skeletal system. All these 24 patients received systemic (adjuvant) therapy after surgery. Ten patients had micrometastases, although in 5 of them both the postoperative bone scan and X-rays showed no pathological results. In 10 women with histologically negative bone biopsies, metastases to the bone were diagnosed by bone scan and radiological methods. Random perioperative iliac bone biopsy cannot be recommended in patients with primary breast cancer. Iliac crest biopsy is relevant in certain scenarios (e.g. suspected recurrence, doubtful bone scan).

Aged↗

PubMed1998

Tandem and triple high-dose chemotherapy with autologous stem cell rescue in metastatic breast cancer.

The purpose of this phase II study was to evaluate the therapeutic efficacy and toxicity of a tandem or triple high-dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (PBSCT) in patients with metastatic breast cancer (MBC) as first line chemotherapy. Conventional chemotherapy consisted of two cycles of epirubicin 120 mg/m2 and ifosfamide 7500 mg/m2 in the case of tandem HDC and one cycle of paclitaxel 135 mg/m2, epirubicin 90 mg/m2 and ifosfamide 6000 mg/m2 in the case of triple HDC. Tandem HDC was composed of two cycles of epirubicin 180 mg/m2, ifosfamide 12000 mg/m2 and carboplatin 900 mg/m2. In the case of triple HDC, paclitaxel 180 mg/m2, etoposide 1500 mg/m2 and thiotepa 600 mg/m2 was added as the third cycle. Patients with tandem HDC (n = 20) were evaluable for both survival and toxicity, and patients with triple HDC (n = 21) only for toxicity because of short-term follow-up. Both tandem and triple HDC were well tolerated and could be safely administered. Non-hematological WHO grade 3 or 4 toxicities were mucositis (8), temporary renal insufficiency (1), myocardial infarction (1), and neuropathy (1). No toxic death occurred. The Kaplan-Meier estimates for 44-months without progression and the overall survival were 12% and 38% respectively. The median survival was 22 months (95% CI: 7.4-51.7 months) and the median progression-free interval 14 months (95% CI: 5.1-43.7 months). In a population with an unfavorable prognosis, tandem HDC showed similar efficacy as to that described in other phase II studies. Triple HDC seems not to improve patient outcome compared to tandem HDC, but a long-term follow up is required.

Adult↗

PubMed1998

Adhesion formation of the parietal and visceral peritoneum: an explanation for the controversy on the use of autologous and alloplastic barriers?

OBJECTIVE: To compare formation of adhesions after injury to both parietal and visceral peritoneum and to determine the benefit of autologous transplants and alloplastic barriers in adhesion prevention. DESIGN: Experimental prospective animal study and prospective randomized clinical study. SETTING: An academic research environment. PATIENT(S): Forty women undergoing laparoscopy for endometriosis treatment. INTERVENTION(S): In 60 rats, either the visceral or parietal peritoneum was injured and covered with autologous peritoneal transplants in half of the animals. The formation of adhesions was assessed 21 days postoperatively. In women, adhesions were evaluated 3 months after surgery with or without placement of alloplastic barriers on visceral lesions. MAIN OUTCOME MEASURE(S): Adhesions evaluated according to a scoring system. RESULT(S): Adhesions after injury of the visceral peritoneum in rats were significantly more severe than those from the parietal peritoneum. Autologous peritoneal transplants led to fewer adhesions especially after serosal injuries. Female volunteers treated with alloplastic barrier material showed less severe adhesions than the control group. CONCLUSION(S): The present data indicate that the potential to form adhesions is significantly higher in visceral than in parietal peritoneal lesions. The development of adhesions after injury to the visceral peritoneum could be reduced by a synthetic barrier material.

Animals↗

PubMed1998

Intraluminal ultrasound imaging of the fallopian tube wall: results of standardized in vitro investigations of pig and human tubal specimens.

OBJECTIVE: To investigate to what extent anatomic structures of the tubal wall can be identified reproducibly and whether altered areas can be detected and delimited by intraluminal ultrasound. DESIGN: Standardized in vitro experiment with descriptive evaluation of findings, comparative analysis of apparative and morphologic data, and determination of interobserver variability (video documentation, blinded reviewer). SETTING: Department of Gynecology and Obstetrics, University of Heidelberg, Germany. SPECIMEN(S): Seventy-two human and pig fallopian tubes. INTERVENTION(S): Catheterization with a 2.9F or 3.2F ultrasound catheter and sonographic depiction of the fallopian tube, with either simultaneous manual and sonographic wall-thickness measurement or coagulation of the tubal wall. MAIN OUTCOME MEASURE(S): A correlation coefficient of r = 0.76 for manual and sonographic tubal wall measurements and K = 0.88 (with 95% confidence interval of 0.74-1.0) for interobserver variability in recognizing coagulated areas. RESULT(S): Tubal wall anatomy and artificially altered (coagulated) areas were displayed reproducibly with intraluminal ultrasound, thus giving a characteristic, recognizable pattern of the tubal wall. CONCLUSION(S): These in vitro experiments provide evidence that intraluminal ultrasound may expand the current diagnostic possibilities in cases of tubal pathology, providing nonsurgical access to the tubal wall.

Animals↗

PubMed1998

Extensive and predominant in situ component in breast carcinoma: their influence on treatment results after breast-conserving therapy.

Intramammary tumour recurrence is one of the most important problems in breast-conserving therapy. We reviewed a series of 957 patients treated with breast-conserving therapy for primary invasive breast carcinomas between 1 January 1985 and 31 December 1992 at the University of Heidelberg. All histological slides were re-evaluated for risk factors with special emphasis on the extent and subclassification of the in situ tumour and the margin status. Six parameters were identified as significant risk factors for intramammary recurrence in the univariate analysis, including extensive or predominant in situ component (EIC, with at least twice the greatest dimension of the invasive tumour component), histological grade, angioinvasion, lobular tumour type, involved resection margin and lymph node status. The presence of an EIC was statistically correlated with low tumour grade, tumour at the resection margins and in re-excision specimens and with multifocal tumour invasion. Multivariate logistic regression analysis revealed that EIC (relative risk (RR) = 1.9), tumour grade (RR = 1.76), angioinvasion (RR = 1.34), lobular tumour type (RR = 1.65) and young age (< or = 40 years, RR = 1.39) were independent predictors of local recurrence. When combining these factors in a linear model, the simultaneous presence of at least two of the five risk factors predicted a 5-year risk of intramammary recurrence of 20.9% compared with a risk of only 1-5% when none or one of these risk factors were identifiable. We conclude that the risk of subsequent intramammary recurrence after breast-conserving therapy can be estimated from a scoring system that includes four histological risk factors and the patient's age.

Adenocarcinoma, Mucinous↗

PubMed1998

Prognostic relevance of cathepsin D detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

Patients with an elevated level of cathepsin D in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of cathepsin D detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both anterior iliac crests in 290 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: BM2, which detects tumour-associated glycoprotein TAG 12, which is typically expressed by almost all breast cancer cells, and the anti-cathepsin D antibody. 67 of 149 BM2-positive women (45%) developed metastatic disease (median follow-up time: 69 months). Of these, 15 were cathepsin D-positive (22%). Patients with cathepsin D-positive cells in bone marrow (n = 26; 9%) had a significantly shorter metastasis-free interval (38 months) compared with women who were cathepsin D-negative (64.5 months). The worst prognosis was seen in patients positive for both markers (30.5 months), followed by those who were cathepsin D-negative and BM2-positive (48 months). The detection of cathepsin D on disseminated tumour cells characterises a subgroup of patients with a poorer prognosis who should undergo more aggressive adjuvant systemic therapy.

Bone Marrow↗