SCC (squamous cell carcinoma) antigen is a subfraction of tumour antigen TA-4 isolated from cervical squamous cell carcinomas. Serum concentrations of SCC antigen were measured by radioimmunoassay in 382 control subjects, 70 women with cervical intraepithelial neoplasia (CIN), 517 with cervical carcinoma and 203 with other gynaecological carcinomas. Elevated SCC antigen levels (greater than 2.5 ng/ml) were found in 4% of normal controls, in 7% of women with CIN I-III, in 2%-23% with various forms of genital adenocarcinomas, in 55% with primary and in 76% of those with recurrent cervical squamous cell carcinoma. The positivity rate of the antigen was correlated with tumour stage (FIGO) and lymph node involvement of primary cervical squamous cell carcinomas. During long-term follow-up serum levels of SCC antigen were found to be concordant with tumour activity in 74% of cases. Patients with still elevated marker levels after therapy had twice the recurrence rate of women with normal serum values. Routine determination of SCC antigen during follow-up of cervical cancer is recommended.

BACKGROUNDPatients with invasive hydatidiform moles (IHM) have a good prognosis. Even if disease has spread, monocytostatic treatment might be sufficient if the diagnosis has been histologically confirmed. Established classifications divide gestational trophoblastic disease (GTD) including choriocarcinoma into cases with "high" and "low" risk. Without respect to histology "high-risk" cases are recommended to obtain polychemotherapy.CASEA 40-year-old nullipara underwent hysterectomy for persistent vaginal bleeding after she had already been treated with curettage for hydatidiform mole. An IHM was pathohistologically confirmed. There were no signs of pulmonary spread or other metastases at the time of surgery. Postsurgically persistent beta-hCG levels lead to thorough staging, which revealed multiple pulmonary metastases and a vaginal metastasis. Despite metastasizing GTD with poor prognosis criteria she was treated with single agent therapy. Eight cycles of two weekly methotrexate (MTX) were administered. All sites of metastases responded and our patient is still fine after one year of follow-up.CONCLUSIONWith respect to this and other reports monochemotherapy can be a reasonable primary treatment for metastatic IHM.

Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects.Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors.Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials.For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, >= 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments.For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes.Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.

Background: The osteoclast-specific active TRAP 5b isoform is detectable in serum and claimed to be a specific marker of bone resorption. The present study was undertaken to evaluate the usefulness of TRAP 5b as a serum marker of bone resorption it? breast cancer patients with bone metastases. Materials and Methods: TRAP 5b serum levels were measured in 192 samples from patients with breast cancer with and without bone metastases and in 53 healthy pre- and postmenopausal women using the enzyme immunoassay Bone-TRAP(R) Results: Serum levels of TRAP 5b were significantly higher in patients with breast cancer and clinical signs of bone metastases before therapy than in healthy women. There was also a significant difference between patients with bone metastases before and during bisphosphonate therapy, indicating a reduction of bone alteration under this treatment. The subgroup with progression of bone metastases tinder bisphosphonate therapy showed the highest difference in TPAP 5b concentrations compared to patients with stable disease. Conclusion: Serum TRAP 5b levels are elevated in patients with bone metastases and breast cancer. The TRAP 5b levels decline tinder bisphosphonate therapy when no progression is detectable. When progress of the bone metastases occurs, TRAP 5b levels rise again. Therefore, active TRAP 5b seems to be a useful serum marker for bone metastases in breast cancer patients, especially to detect progressive disease under bisphosphonate treatment. Further studies with larger numbers of patients are required to confirm these data.

BACKGROUND:The c-erbB-2 (HER2/neu) receptor is a transmembrane phosphoglycoprotein associated with multiple signal transduction pathways. Its overexpression in breast cancer tissue has been correlated with poor prognosis. We report preliminary data of an ongoing study in invasive breast cancer patients exploring c-erbB-2 protein overexpression in relation to established tumor characteristics of prognostic value.MATERIALS AND METHODS:In primary breast carcinoma samples from 115 women undergoing surgery in our department in 1999, a polyclonal rabbit antibody to human c-erbB-2 oncoprotein was used for immunohistochemical assessment of the c-erbB-2 expression in formalin-fixed paraffin-embedded material. The data were statistically correlated with classical histopathological parameters.RESULTS:In the studied collective of mainly postmenopausal women (75%) with a high rate of early stage breast cancer (88% pT1 + 2), there was no significant relation between c-erbB-2 overexpression, classified as positive in 42% of the samples, and lymph node involvement, tumor size and grade, or hormone receptor status.CONCLUSION:Using the presented highly sensitive method, no association between c-erbB-2 expression and established prognostic factors was found. These data are in line with reports that the value of HER2/neu determination is not fully clarified for the preadjuvant evaluation of newly diagnosed breast cancer patients.

Background: The vascular endothelial growth factor (VEGF) is the angiogenic growth factor most strongly implicated in tumor angiogenesis. Its special role in the pathophysiology of ovarian cancer emerges from its dual functional capability as an endothelial cell mitogen and a potent stimulator of vascular permeability lending to the characteristic ascites accumulation in this disease. The aim of our study was to analyze the prognostic value of serum VEGF (sVEGF) as a tumor. marker in ovarian cancer. Patients and Methods.. 41 patients with ovarian carcinomas were included in the study. Venous blood was taken from all patients preoperatively. From 15 patients an additional postoperative blood sample was drawn. sVEGF was measured in duplicate using a commercially available ELISA-kit. Results. The mean sVEGF level for the ovarian cancer patients was 522 +/- 321 pg/ml (SD) (median: 440; range: 55-1263 pg/ml) No statistically significant correlation could be found between sVEGF concentrations and age, histologic type or FIGO-stage. sVEGF values four week after surgery were significantly lower than those before treatment (p = 0.002). In patients after radical surgery sVEGF values dropped or stayed stable below the cut-off more often than in patients with residual disease. In the univariate analysis, improved overall survival (OS) was found for ovarian cancer patients with a sVEGF below the cut-off value of 440 pg/ml (p = 0.017). sVEGF was also tested in a multivariate analysis together with residual disease and FIGO-stage using the Cox's proportional hazard model. In the final model only residual disease had nit independent influence on OS (p = 0.018). Conclusion: sVEGF levels decrease significantly after cytoreductive therapy and might indicate treatment efficiency. According to our study, sVEGF is not an independent prognosticator of survival for ovarian cancer.

Background: CA 125 is the most important tumor marker in ovarian cancer. Due to its low specificity and the fact that some ovarian malignancies do not produce considerable amounts of CA 125 a combination with the Cancer Associated Serum Antigen (CASA) may reflect more accurately the clinical situation. Materials and Methods: CA 125 and CASA determination was performed in sera of 78 patients with advanced ovarian cancer pre- and postoperatively, monthly during chemotherapy and during follow-up care. The cut-off values for CASA were 4 U/ml, for CA 125 35 U/ml and 65 U/ml, respectively. Results: In the detection of advanced ovarian cancer a combination of both tumor markers was superior to the use of either CASA or CA 125 alone. In the follow-up situation CA 125 with the 35 U/ml cut-off showed the highest sensitivity. Both markers had similar prognostic relevance when marker levels three months after surgery were used. Conclusion: CA 125 and CASA have similar characteristics in preoperative diagnosis and postoperative follow-up. In clinical situations with inconclusive or negative CA 125 serum values CASA is helpful to improve management of patients with advanced ovarian cancer.

BACKGROUND The clinical usefulness of tumor markers in the follow-up care of invasive breast cancer is controversial. METHODS In 1228 serum samples of 664 women with history of breast cancer, the diagnostic accuracy and predictive power of CEA and CA 15-3 for the detection of disease relapse was determined prospectively by analyzing the clinical course for at least 6 months after the measurement of the tumor markers in 1994. RESULTS A total of 76 patients relapsed during the period of study. The diagnostic accuracy was 83% for CEA and 88% for CA 15-3. CEA and CA 15-3 had a positive predictive value of 27% and 47% as well as a negative prediction of 91% and 93%, respectively. CONCLUSIONS The low positive predictive value and sensitivity of these tumor markers clearly limit their clinical utility. Therefore, the effectiveness of routine determinations during the follow-up seems questionable.

BACKGROUND Tumour angiogenesis and microvessel density are of prognostic significance in several human neoplasia. To investigate how tumour vascularity correlates with disease-free survival microvessel density was assessed in 38 patients with ovarian cancer using the highly specific endothelial marker CD 34. METHODS Representative specimens were obtained and stained using monoclonal CD 34 antibodies. The microvessels were quantified at 200x and 400x magnification in the most active areas of neovascularisation. Degree of angiogenesis was correlated with histologic tumour type, grading, and tumour stage. Furthermore, survival was calculated using Kaplan-Meier analysis and results again correlated with the microvessel count. RESULTS No correlation was found between microvessel density, histologic type, grading, and FIGO stage. Patients with a vessel count more than 40 (200x magnification) had a statistically significant lower overall survival (p = 0.022). CONCLUSION Our results indicate that CD 34 is a useful marker in determining tumour neovascularisation which might be of prognostic relevance in patients with ovarian cancer.

Background: Angiogenesis is necessary for growth and invasiveness of malignant tumors. Vascular endothelial growth factor (VEGF) is considered to play a key role in tumor angiogenesis. Few data are available with regard to serum levels of VEGF in patients with ovarian tumors. We investigated the diagnostic value of serum VEGF in patients with ovarian neoplasms. Materials and Methods: 61 patients with ovarian neoplasms (41 ovarian carcinomas, 20 cystadenomas) and 20 healthy women were included into the study. VEGF serum concentrations were determined by a commercially available ELISA. Results: Statistical analysis revealed significant differences in VEGF serum values of ovarian cancer patients vs. healthy controls or patients with cystadenomas. No difference could be seen between serum levels of healthy controls and women with benign ovarian tumors. For ovarian cancer patients vs. normal controls a sensitivity of 71% and a specificity of 65% resulted. The sensitivity and specificity of cancer patients vs. patients with benign neoplasms were 71% and 65%, respectively.Conclusion: Our results suggest that VEGF has potential as a serum marker with diagnostic relevance in ovarian neoplasms.

BACKGROUNDTo assess the differential diagnostic potential of physical examination, ultrasound, the serum CA 125 assay, and serum CA 72-4 assay, and the contribution of each parameter to a logistic model predicting the probability of malignancy in postmenopausal patients presenting with a pelvic mass.PATIENTS AND METHODSIn a multicenter, prospective study a total of 155 patients were evaluated preoperatively using a standard protocol for pelvic examination, transvaginal (occasionally additional abdominal) ultrasound, and serum CA 72-4 (cutoff level 3 U/ml) and CA 125 (cutoff level 35 U/ml).RESULTSFifty-nine malignant (39%) and 92 benign (61%) pelvic tumors were found in addition to 4 borderline tumors (3%). Forty-three patients appeared to have ovarian carcinoma, FIGO Stage III or IV in 28 cases. Borderline tumors were excluded from the statistical calculations. The diagnostic accuracy of each single parameter, i.e., pelvic examination, ultrasound, and serum CA 125 and CA 72-4 in discriminating between benign and malignant pelvic masses gave highly similar results (81, 76, 78, and 81% respectively). Best sensitivity was found in pelvic examination (92%); best specificity was found in CA 72-4 (93%). Using logistic regression analysis the power of pelvic examination appeared to be the most relevant (adjusted odds ratio 12.1), followed by ultrasound (odds ratio 9.7), serum CA 125 (odds ratio 5.0), and serum CA 72-4 (odds ratio 4.9). Age appeared to be nonpredictive. The logistic model gives a correct prediction in 87% of all cases.CONCLUSIONSThe addition of serum CA 72-4 to the combination of pelvic examination, ultrasound, and serum CA 125 leads to an improved discrimination between malignant and benign pelvic masses.

AIM:To test which immunohistochemically detected tumour parameters are predictive of outcome in endometrial carcinoma.METHODS:A retrospective study of 300 patients diagnosed with endometrial carcinoma between 1980 and 1985, ensuring a follow up of at least 10 years. Paraffin wax embedded tissues from 236 patients with endometrial carcinoma were evaluated in terms of histological tumour type and grade, stage of disease, and certain immunohistochemical biological parameters. These parameters included the expression of oestrogen and progesterone receptors, the expression of p53 protein, the expression of the c-erbB-2 oncoprotein, and the expression of protease cathepsin D, together with the rate of cell proliferation.RESULTS:Using univariate analysis, the following parameters correlated significantly with adjusted survival: histological type (p = 0.025), grade (p = 0.00003), FIGO stage (p < 0.00001), proliferation rate (p = 0.00002), oestrogen receptor expression (p = 0.007), progesterone receptor expression (p = 0.0092), and p53 expression (p = 0.00028). These parameters also correlated significantly with both disease free and overall survival. There was a weak correlation of cathepsin D expression with survival, but no correlation of c-erb B-2 expression with survival. Using multivariate analysis, only FIGO stage (p = 0.0021), histological grade (p = 0.005), and proliferation rate (p = 0.0007) remained statistically significant prognosticators of adjusted survival as well as of disease free and overall survival.CONCLUSIONS:In addition to conventional histological parameters, the immunohistochemical determination of proliferative activity could contribute to the identification of a high risk subgroup of endometrial carcinomas. The other parameters tested were not of significant additional predictive value.

Background There have been many randomised trials of adjuvant prolonged polychemotherapy among women with early breast cancer, and an updated overview of their results is presented.Methods In 1995, information was sought on each woman in any randomised trial that began before 1990 and involved treatment groups that differed only with respect to the chemotherapy regimens that were being compared. Analyses involved about 18 000 women in 47 trials of prolonged polychemotherapy versus no chemotherapy, about 6000 in 11 trials of longer versus shorter polychemotherapy, and about 6000 in 11 trials of anthracycline-containing regimens versus CMF (cyclophosphamide, methotrexate, and fluorouracil).Findings For recurrence, polychemotherapy produced substantial and highly significant proportional reductions both among women aged under 50 at randomisation (35% [SD 4] reduction; 2p<0.00001) and among those aged 50-69 (20% [SD 3] reduction; 2p<0.00001); few women aged 70 or over had been studied. For mortality, the reductions were also significant both among women aged under 50 (27% [SD 5] reduction; 2p<0.00001) and among those aged 50-69 (11% [SD 3] reduction; 2p=0.0001). The recurrence reductions emerged chiefly during the first 5 years of follow-up, whereas the difference in survival grew throughout the first 10 years. After standardisation for age and time since randomisation, the proportional reductions in risk were similar for women with node-negative and node-positive disease. Applying the proportional mortality reduction observed in all women aged under 50 at randomisation would typically change a 10-year survival of 71% for those with node-negative disease to 78% (an absolute benefit of 7%), and of 42% for those with node-positive disease to 53% (an absolute benefit of 11%). The smaller proportional mortality reduction observed in all women aged 50-69 at randomisation would translate into smaller absolute benefits, changing a 10-year survival of 67% for those with node-negative disease to 69% (an absolute gain of 2%) and of 46% for those with node-positive disease to 49% (an absolute gain of 3%). The age-specific benefits of polychemotherapy appeared to be largely irrespective of menopausal status at presentation, oestrogen receptor status of the primary tumour, and of whether adjuvant tamoxifen had been given. In terms of other outcomes, there was a reduction of about one-fifth (2p=0.05) in contralateral breast cancer, which has already been included in the analyses of recurrence, and no apparent adverse effect on deaths from causes other than breast cancer (death rate ratio 0.89 [SD 0.09]). The directly randomised comparisons of longer versus shorter durations of polychemotherapy did not indicate any survival advantage with the use of more than about 3-6 months of polychemotherapy. By contrast, directly randomised comparisons did suggest that, compared with CMF alone, the anthracycline-containing regimens studied produced somewhat greater effects on recurrence (2p=0.006) and mortality (69% vs 72% 5-year survival; log-rank 2p=0.02). But this comparison is one of many that could have been selected for emphasis, the 99% CI reaches zero, and the results of several of the relevant trials are not yet available.Interpretation Some months of adjuvant polychemotherapy (eg, with CMF or an anthracycline-containing regimen) typically produces an absolute improvement of about 7-11% in 10-year survival for women aged under 50 at presentation with early breast cancer, and of about 2-3% for those aged 50-69 (unless their prognosis is likely to be extremely good even without such treatment). Treatment decisions involve consideration not only of improvements in cancer recurrence and survival but also of adverse side-effects of treatment, and this report makes no recommendations as to who should or should not be treated.