Validation of the S classification of sentinel lymph node and microanatomic location of sentinel lymph node metastases to predict additional lymph node involvement and overall survival in breast cancer patients.

BACKGROUND: Most patients with a positive sentinel lymph node (SN) have no further metastases in the axillary lymph nodes and may therefore not benefit from axillary lymph node dissection. In patients with melanoma, evaluation of the centripetal depth of tumor invasion in the SN, also known as the S classification of SN, and microanatomic localization of SN metastases were shown to predict non-SN involvement. This phenomenon has been less extensively studied in breast cancer. We sought to validate the S classification and microanatomic location of SN metastases in breast cancer patients with regard to their predictive value for non-SN involvement and overall survival (OS). METHODS: A total of 236 patients with positive SN followed by axillary lymph node dissection were reevaluated according to the S classification and the microanatomic location of SN (subcapsular, parenchymal, combined subcapsular and parenchymal, multifocal, extensive) metastases to predict the likelihood of non-SN metastases and OS. RESULTS: S classification and the microanatomic location of SN metastases were significantly correlated with non-SN status (P < 0.001). Especially patients with a maximum depth of invasion ≤0.3 mm (stage I according to the S classification) and those with SN metastases only in subcapsular location had a low probability of further non-SN metastases (7.8 and 6.1%) and a good prognosis for OS. CONCLUSIONS: S classification and microanatomic location of SN metastases predicts the likelihood of non-SN involvement. Especially patients with subcapsular or S stage I metastases have a low probability of non-SN metastases and a good prognosis for OS.

Serum C-reactive protein as independent prognostic variable in patients with ovarian cancer.

PURPOSE: To evaluate serum C-reactive protein (CRP) as prognostic variable in patients with epithelial ovarian cancer (EOC). EXPERIMENTAL DESIGN: In a multicenter study, preoperative serum CRP was evaluated in 623 patients with EOC. Results were correlated with clinical data. RESULTS: Mean (SD) preoperative serum CRP was 3.6 (4.8) mg/dL. Serum CRP was significantly associated with International Federation of Gynecologists and Obstetricians stage (P < 0.001) and postoperative residual tumor mass (P < 0.001) but not with histologic grade (P = 0.1) and type (P = 0.7), patients' age (Pearson's correlation coefficient = 0.05; P = 0.2), and serum CA 125 (Pearson's correlation coefficient = 0.02; P = 0.6). Patients with platinum-resistant EOC had significantly higher CRP serum levels compared with patients with platinum-sensitive EOC [6.0 (6.6) mg/dL versus 2.8 (3.8) mg/dL; P < 0.001]. Higher International Federation of Gynecologists and Obstetricians stage (P < 0.001), presence of postoperative residual tumor mass (P < 0.001), tumor grade (P = 0.001), serum CA 125 (P = 0.03), and serum CRP (P = 0.001) were independently associated with overall survival. Patients with serum CRP < or =1 mg/dL versus >1 mg/dL had an overall 5-year survival of 82% versus 58.5% (P < 0.001). CONCLUSION: Serum CRP can be seen as a novel, widely available independent prognostic variable of ovarian cancer.

Erythropoetin beta twice weekly versus standard therapy in patients with gynaecological malignancies--a randomised Austrian AGO trial.

BACKGROUND: The influence of two regimens of erythropoetin beta on haemoglobin level, quality of life (QoL) and side-effects in patients with gynaecological malignancies was assessed. PATIENTS AND METHODS: A total of 119 patients during chemotherapy were randomised to either standard therapy with 10,000 IU erythropoetin beta three times a week (group A) or 20,000 IU twice a week (group B). Haemoglobin level and QoL were measured. Characteristics of the study population were analysed with descriptive statistical methods. Analysis of variance for repeated measurements was performed with haemoglobin level as dependent variable, and time and study arms as factors. RESULTS: The rise in haemoglobin levels and QoL improvement were significant, without any difference between study arms. Adverse events were similar, except significantly more thromboembolic events in group B (0 vs. 8 events; p = 0.003). CONCLUSION: Our results show similar improvements in haemoglobin level and QoL, but raise the question whether less frequent dosing regimes may result in increased rates of thromboembolic events.

S-classification of sentinel lymph node predicts axillary nonsentinel lymph node status in patients with breast cancer.

BACKGROUND: One-half of breast cancer patients with positive sentinel lymph node (SN) have no further metastases in the axillary lymph node basin. The aim of the present study was to identify patients with positive SN who are unlikely to have further metastases in the axillary lymph node basin, using a new classification of SN, namely the S-classification. METHODS: Specimens of positive SN were subjected to a pathological review according to the previously published S-classification. S-stages of positive SN were correlated with the status of further metastases in the axillary lymph node basin after axillary lymph node dissection (ALND). RESULTS: Of 117 patients who underwent sentinel lymph node biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND. The occurrence of positive nonsentinel nodes was significantly related to the S-stage of SN. No patient with stage SI had additional metastases in the nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9% of patients with SIII disease had other non-SN that were metastatic. CONCLUSION: S-stages of positive SN are highly predictive for axillary nonsentinel node status. Especially patients with SI sentinel node metastases appear to be at low risk for further nonsentinel node metastases.

Estrogen receptor beta and matrix metalloproteinase 1 are coexpressed in uterine endometrium and endometriotic lesions of patients with endometriosis.

OBJECTIVE: To evaluate the local matrix metalloproteinase 1 (MMP-1), estrogen receptor (ER) alpha, and ERbeta protein expression in eutopic and dystopic tissue from patients with endometriosis and to compare the endometrial expression pattern in women with and without endometriosis. DESIGN: Immunohistochemical analysis of MMP-1, ERalpha, and ERbeta in paired samples of uterine and endometriotic endometrium from cycling women with endometriosis and in endometrial tissue from 37 healthy women. SETTING: Research laboratory at a medical school. PATIENT(S): Thirty-seven matched samples from endometriotic and corresponding endometrial biopsies obtained during the proliferative and secretory phase. Thirty-seven endometrial biopsies obtained from healthy women during comparable cycle phases. INTERVENTION(S): Sampling of endometrial and endometriotic tissue. MAIN OUTCOME MEASURE(S): Matrix metalloproteinase 1, ERalpha, and ERbeta protein expression in paraffin-embedded tissue biopsies was measured by IHC. RESULT(S): In patients with endometriosis, epithelial and stromal cells from endometriotic lesions both express significantly higher levels of MMP-1 and lower levels of ERalpha than corresponding cells in uterine endometrium. Endometriotic epithelium also expresses higher levels of ERbeta than of ERalpha. In both endometrial glands and corresponding endometriotic epithelium, the distribution of MMP-1 is correlated with ERbeta. No significant differences in endometrial ERalpha, ERbeta, or MMP-1 expression could, however, be detected when patients with endometriosis and healthy controls were compared. CONCLUSION(S): We have shown that MMP-1 and ERbeta are coexpressed and up-regulated in endometriotic lesions, whereas local ERalpha expression is down-regulated. The altered ERbeta/ERalpha ratio in endometriotic glands suggests that estrogenic effects on MMP-1 are primarily mediated via ERbeta, and the local control of MMP-1 in eutopic endometrium is not different from that observed in healthy cycling women.

Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque.

Defined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.03 +/- 13.00 pg/cm(2) luminal plaque surface). Active TF was sedimented, indicating that TF was associated with membranes. Coronary blood was drawn from 6 patients undergoing coronary interventions with the distal protection device PercuSurge GuardWire (Traatek, Miami, FL). Fine particulate material that was recovered from coronary blood showed TF activity (corresponding to 91.1 +/- 62.16 pg/mL authentic TF). To examine the role of TF in acute coronary NR, blood was drawn via a catheter from coronary vessels in 13 patients during NR and after restoration of flow. Mean TF antigen levels were elevated during NR (194.3 +/- 142.8 pg/mL) as compared with levels after flow restoration (73.27 +/- 31.90 pg/mL; P =.02). To dissect the effects of particulate material and purified TF on flow, selective intracoronary injection of atherosclerotic material or purified relipidated TF was performed in a porcine model. TF induced NR in the model, thus strengthening the concept that TF is causal, not just a bystander to atherosclerotic plaque material. The data suggest that active TF is released from dissected coronary atherosclerotic plaque and is one of the factors causing the NR phenomenon. Thus, blood-borne TF in the coronary circulation is a major determinant of flow.