Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy.

PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important. PATIENTS AND METHODS: According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients' prognosis. RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P =.032 and P =.014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P =.031) in our series. CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.

Evaluation of mammographic breast lesions with Tc-99m sestamibi scintimammography and contrast enhanced MRI.

Scintimammography using Tc-99m sestamibi and contrast enhanced MRI were performed in order to determine the accuracy of both methods in the diagnostic work up of patients with suspicious or indeterminate preliminary diagnosis. 25 controls and 56 patients (14 with suspicious and 42 with indeterminate preliminary diagnoses), in whom physical examination and/or mammography warranted breast biopsy, underwent prone planar scintimammography. Sestamibi uptake was scored visually and measured using the ROI technique to enable semiquantitative evaluation. The patient group additionally underwent plain and contrast enhanced MRI. Visually determined signal increase following application of Gd-DTPA was compared with scintigraphic findings and final histopathologic results. Sensitivity and specificity of semiquantitative scintimammography for diagnosing breast cancer was 88% and 87%, respectively. Based on ROC analysis a target/non target ratio R > 1.3 was shown to be the optimal threshold for separating benign from suspicious scintigraphic diagnoses. MRI reading provided a slightly higher sensitivity (91%), but a considerable lower specificity (52%) due to contrast enhancement of different benign lesions. In the clinically important patient subpopulation with indeterminate results from previous diagnostic procedures, sensitivity of scintimammography fell to 79%, while specificity remained at 87%. MRI revealed a higher sensitivity of 89% and a lower specificity of 52%. Our data indicate that semiquantitative scintimammography using Tc-99m sestamibi provides a comparable sensitivity to contrast enhanced MRI in the assessment of breast cancer. The latter does not reduce the number of biopsies yielding benign results due to the high number of false positive diagnoses. Therefore, scintimammography seems to be the preferable tool in the diagnostic work-up of patients with indeterminate mammographic diagnoses.

Soluble interleukin-2 receptor and soluble CD8 in liver cirrhosis and obstructive jaundice.

Activated lymphocytes secrete soluble interleukin-2 receptor (sIL-2R); CD8-positive lymphocytes secrete soluble CD8 (sCD8). Liver dysfunction in cirrhosis and obstructive jaundice is known to result in depressed cellular immunity. To evaluate whether this is due to real inactivation of the immune system, we measured sIL-2R and sCD8 in the serum of 46 patients with liver cirrhosis, 25 patients with obstructive jaundice, 32 patients with alcoholic liver disease without evidence of cirrhosis, 23 healthy persons and 43 patients with unrelated disease. sIL-2R in patients with cirrhosis (mean +/- s.e.m. 1499 +/- 140 U/ml) and obstructive jaundice (1517 +/- 204) was significantly increased compared with healthy subjects (363 +/- 29) and patients with unrelated diseases (685 +/- 92); sCD8 was significantly increased in patients with cirrhosis (737 +/- 63) but not in patients with obstructive jaundice (419 +/- 32) compared with healthy subjects (322 +/- 23) and patients with unrelated diseases (375 +/- 22). No difference was found between patients with cirrhosis due to alcohol abuse (n = 15) and chronic hepatitis B (n = 6). The Child-Pugh score had no significant influence on the sIL-2R or sCD8 value. In obstructive jaundice, sIL-2R correlated with alkaline phosphatase as marker of cholestasis (r = 0.43). These data show that in spite of the apparent depressed cellular immune defense both in liver cirrhosis and obstructive jaundice there is a general activation of the immune system but the CD8+ cell compartment is only activated in liver cirrhosis. The great changes of sIL-2R and sCD8 in liver dysfunction are important for the interpretation of studies using these serum proteins as markers for immune activation.