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BACKGROUND: We performed a retrospective study to establish the optimal radiological criteria for axillary lymph node metastases from breast cancer by measuring all dissected nodes, and to determine whether magnetic resonance imaging (MRI) could reliably reveal axillary involvement. METHODS: Pathological findings and MRI scans of 202 patients with invasive breast cancer were reviewed. The long- and short-axis dimensions of all level I an II lymph nodes were measured microscopically, and then the long-to-short axis (L/S) ratio of each node was calculated. These parameters were compared with pathological nodal status to define radiological criteria for axillary involvement. MRI was carried out using T1-weighted spin-eho sequences in the coronal and sagittal planes. On MRI, every detected lymph node was measured and the shape ofthe nodal cortex was also examined. Then the diagnostic ability of MRI was assessed using these morphologic criteria. RESULTS: On histopathological examinations of 4043 dissected lymph nodes, a long-axis dimension of 10 mm or larger combined with a long-to-short axis ratio of less than 1.6 was the most accurate criteria for predicting lymph node metastases. On MRI, eccentric cortical hypertrophy was seen in only metastatic axillae.When these morphologic features were used as criteria for malignancy, MRI had asensi-tivity of 79%, a specificity of 93%, and an accuracy of 88%. In 16 of 17 false-negative axillae, MRI showed normally sized lymph nodes (< 10 mm). CONCLUSION: Our study indicates that MRI is a useful diagnostic method for the evaluation of axillary nodal status, but is limited in the detection of small metastatic lymph nodes.

A growing body of evidence supports the hypotheses that retinoic acid receptor beta2 (RAR beta2) is a tumor suppressor gene. Although the loss of RAR beta2 expression has been reported in many malignant tumors, including breast cancer, the molecular mechanism is still poorly understood. We hypothesized that loss of RAR beta2 activity could result from multiple factors, including epigenetic modification and loss of heterozygosity (LOH). Using methylation-specific polymerase chain reaction and LOH analysis, we found that biallelic inactivation via epigenetic changes of both maternal and paternal alleles, or epigenetic modification of one allele combined with genetic loss of the remaining allele, could completely suppress RAR beta2 expression in breast cancer. Thus, it is possible that substantial numbers of human cancers arise through suppressor gene silencing via epigenetic mechanisms that inactivate both alleles. Because of this, chromatin-remodeling drugs may provide a novel strategy for cancer prevention and treatment.

Determination of the standard elimination kinetics of tumor markers will be helpful in the diagnosis of malignancies. We analyzed the disappearance curves for serum tumor marker levels after resection of intrathoracic malignancies. Serum levels of CEA, SLX, AFP, CA 19-9, SCC, TPA and CYFRA were measured several times after surgery in a total of 40 patients. To obtain precise biological half-lives, we applied non-linear least square analysis, taking into consideration the possibility of residual tumor cells. Disappearance curves were monophasic for CEA, SCC, TPA, CYFRA and SLX and biphasic for CA 19-9 and AFP. Temporary elevation of serum levels after surgery was observed for SCC, TPA and CYFRA. The average half-lives of CEA, SLX, SCC, TPA and CYFRA were 1.5 days, 2.7 days, 2.2 hours, 2.5 hours and 1.5 hours, respectively. The average half-life of CA 19-9 was 0.5 days in the first compartment and 4.3 days in the second compartment, while that of AFP was 1.0 days and 6.3 days, respectively. These values will be helpful in the interpretation of serum tumor marker levels after surgery.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast carcinomas was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the drugs killing was significantly higher than that of Bcl-2-positive tumors. No relationship between Bax or p53 immunoreactivity and sensitivity for any of anticancer drugs studied was demonstrated. Immunohistochemical results regarding Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a series of anticancer drugs and might be therapeutically useful as an indicator of response to adjuvant chemotherapy for breast cancer.

These results imply that nuclear grade is related to the characteristics of tumor biology, indicating that the morphology and biology of breast cancer are tightly linked. Our present results also suggest that adding the nuclear grade to the pathological diagnosis of invasive breast carcinoma may be clinically useful for predicting tumor behavior, for example aggressiveness, and for prognostication.

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