Dataset Information

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes.

ABSTRACT: BACKGROUND AND OBJECTIVES: In patients with breast cancer (BC), the sentinel node (SN) is the first node in the axillary basin that receives the primary lymphatic flow and can be used to accurately assess the axillary nodal status without removal of the axillary contents. Currently, histology and/or immunohistochemistry are the routine methods of SN analysis. The primary objective of this study was to develop a reproducible reverse transcription (RT) PCR assay, with emphasis on achieving high specificity for accurate detection of BC micrometastases in the SN. To correct for the heterogeneity of BC cells, a multimarker approach was followed, with the further aim of improving the detection rate of the assay. METHODS: In total, 73 markers were evaluated, of which 7 were breast epithelial markers and 66 were either cancer testis or tumour associated antigens. Twelve BC cell lines and 30 SNs (from 30 patients) were analysed using RT-PCR to determine the in vitro and in vivo detection rates for each of the markers. In addition, 20 axillary nodes obtained from a patient with brain death were used as controls to optimise the PCR cycle numbers for all the markers. RESULTS: Of the 30 SNs, 37% (11/30) were positive on haematoxylin and eosin analysis. Extensive immunohistochemical (IHC) analyses of the haematoxylin and eosin negative nodes confirmed the presence of very small numbers of BC cells in an additional 40% (12/30) of SNs. Molecular analysis with the hMAM-A alone identified metastases in 70% (21/30) of SNs. Using MAGE-A3 in combination with hMAM-A identified metastases in 90% (27/30) of patients. Seven SNs (23%) were negative for micrometastases (with haematoxylin and eosin and IHC) but RT-PCR positive for either hMAM-A or MAGE-A3. CONCLUSIONS: As IHC analysis resulted in a 77% detection rate compared with 37% for haematoxylin and eosin analysis, we consider that IHC is essential in order not to miss SN micrometastases. Molecular analysis with hMAM-A and MAGE-A3 allows detection of BC micrometastases with a 90% detection rate. However, the clinical value of histologically negative but RT-PCR positive SNs can only be determined with long term follow up.

SUBMITTER: Abdul-Rasool S

PROVIDER: S-EPMC1860352 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes.

Abdul-Rasool S S Kidson S H SH Panieri E E Dent D D Pillay K K Hanekom G S GS

Journal of clinical pathology 20060301 3

<h4>Background and objectives</h4>In patients with breast cancer (BC), the sentinel node (SN) is the first node in the axillary basin that receives the primary lymphatic flow and can be used to accurately assess the axillary nodal status without removal of the axillary contents. Currently, histology and/or immunohistochemistry are the routine methods of SN analysis. The primary objective of this study was to develop a reproducible reverse transcription (RT) PCR assay, with emphasis on achieving ...[more]

PMID: 16505281

Similar Datasets

Project description:Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination.To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow specimens from patients with early-stage breast cancer.From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1 to T2N0M0 invasive breast carcinoma in a prospective observational study.All 5210 patients underwent breast-conserving surgery and SLN dissection. Bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). Sentinel lymph node specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results.Overall survival (primary end point) and disease-free survival (a secondary end point).Of 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive for tumors. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7%; 95% confidence interval [CI], 95.0%-96.5% for immunohistochemical negative and 95.1%; 95% CI, 92.7%-97.5% for immunohistochemical positive disease; P = .64; unadjusted hazard ratio [HR], 0.90; 95% CI, 0.59-1.39; P = .64). Bone marrow metastases were associated with decreased overall survival (unadjusted HR for mortality, 1.94; 95% CI, 1.02-3.67; P = .04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45-1.71; P = .70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79-4.26; P = .15) was statistically significant on multivariable analysis.Among women receiving breast-conserving therapy and SLN dissection, immunohistochemical evidence of SLN metastasis was not associated with overall survival over a median of 6.3 years, whereas occult bone marrow metastasis, although rare, was associated with decreased survival.clinicaltrials.gov Identifier: NCT00003854.

Dataset Information

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes.

Publications

An evaluation of molecular markers for improved detection of breast cancer metastases in sentinel nodes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure