Occult Metastases in Axillary Lymph Nodes as a Predictor of Survival in Node-Negative Breast Carcinoma with Long-term Follow-up

Abstract

Increased detection rate in the lymph nodes is seen with serial sectioning or immunohistochemistry (IHC), but the importance of occult metastases is not resolved. IHC is still not recommended in routine examination of lymph nodes. Axillary lymph nodes from 385 node-negative breast cancer patients with a median follow-up of 25 years were examined with IHC for cytokeratins, applied on routine sections. The association between classic histopathologic prognostic factors and the presence of occult metastases was evaluated. Metastases were found in 45 of 385 cases (12%), 21 metastases (47%) measured < or =0.2 mm, 8 (18%) were larger than 2 mm; 14 metastases were located in the subcapsular sinus, 22 in the parenchyma of the lymph node; and 51% (23/45) of the metastases were recognized on hematoxylin-eosin staining on "second look." The detection of metastases was significantly associated with the number of sectioned lymph nodes (6% metastases for one to five lymph nodes examined versus 17% for more than five lymph nodes) and with histologic subtype (metastases in 11% of the ductal versus 33% of the lobular carcinomas). No significant association was found between occult metastases and age, tumor size, histologic grade, estrogen or progesterone receptor status, p53, or c-erbB-2. Metastases larger than 2 mm predicted a poorer recurrence-free survival rate for the whole series. A subcapsular location of the metastases was a strong predictor of overall survival. Whether or not the metastases could be identified on hematoxylin-eosin sections did not have any prognostic significance. In the multivariate analysis, histologic grade, tumor size of the primary tumor, progesterone receptor status, and the presence of occult metastasis in the lymph nodes had a prognostic impact on survival with a 25-year follow-up.

The clinical significance of sentinel lymph node micrometastasis in breast cancer

“…Furthermore, in patients who did not receive adjuvant systemic therapy, the prognosis of a single MM was comparable to a single macrometastasis [30]. Negative prognostic impact has also been reported by Reed et al [31]. In their study of 385 women with BC, poorer prognosis was found in those 45 cases with occult metastases compared to their truly node negative counterparts.…”

Relationship between viral factors, axillary lymph node status and survival in breast cancer

“…Axillary lymph node involvement has been recognized as the most important prognostic factor in breast cancer, despite the fact that many other parameters have been evaluated in recent years (O'Hanlon et al 2002;Reed et al 2004). Recently, Reed et al (2004) demonstrated that metastases larger than 2 mm predicted poorer relapse-free survival rate and that subcapsular location of metastases was a strong predictor of overall survival in their sample.…”

Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

“…Estimates of the true false-negative rates for the detection of metastases range from 5 to 15%. 36,37 Analysis of the seven molecular markers tested demonstrated that the majority of mammaglobin/CK19 molecular false positives were also positive with several other breast tumor markers not expressed in the vast majority of H&E-negative samples. Samples demonstrat- ing significant expression of mammaglobin and/or CK19 have a high probability of also expressing the other markers tested, including B305D, GABA, B726, and PDEF, markers previously demonstrated to have increased expression in cancerous breast tissues.…”