Molecular Detection of Micrometastatic Breast Cancer in Histopathology-Negative Axillary Lymph Nodes Correlates With Traditional Predictors of Prognosis

Gillanders, William E.; Mikhitarian, Kaidi; Hebert, Renee; Mauldin, Patrick D.; Palesch, Yuko Y.; Walters, Christian; Urist, Marshall M.; Mann, G. Bruce; Doherty, Gerard M.; Herrmann, Virginia M.; Hill, Arnold D.; Eremin, O.; ElSheemy, Mohammed S.; Orr, Richard K.; Valle, Alvaro A.; Henderson, Michael A.; DeWitty, Robert L.; Sugg, Sonia L.; Frykberg, Eric R.; Yeh, Karen A.; Bell, Richard M.; Metcalf, John S.; Elliott, Bruce M.; Brothers, Thomas E.; Robison, Jacob G.; Mitas, Michael; Cole, David J.

doi:10.1097/01.sla.0000128687.59439.d6

Cited by 104 publications

(102 citation statements)

References 32 publications

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“…The real malignant potential of these cells is not yet known. Nevertheless, as some limitations were observed in our study, more investigations are required to confirm our results by including more patients, especially with advanced-stage breast cancer, and by increasing the sensitivity and specificity of screening methods using a multimarker PCR approach [20] associated with xenografting experiments. Only then can ovarian tissue transplantation be contemplated in patients with advancedstage disease.…”

Section: Resultsmentioning

confidence: 76%

“…In the existing literature on axillary sentinel lymph nodes in breast cancer patients [20,34,46], the discrepancy between histological and immunohistochemical analyses and PCR approaches has already been described. It is most likely explained by the sampling procedure, because the parts of the lymph node analyzed using molecular techniques are different from those examined by histopathology and immunohistochemistry.…”

Section: Quantitative Pcr Analysesmentioning

confidence: 99%

“…To improve the sensitivity of the biomolecular approach, one option is using a multi-marker gene panel [20]. Since circulating tumor cells in a given patient with breast cancer may not express the particular tumor marker being assayed, a multiple marker assay, taking into account tumor heterogeneity and mRNA expression variability, may improve detection [20,39].…”

Section: Quantitative Pcr Analysesmentioning

confidence: 99%

“…Mammaglobin (MGB1) and mammaglobin B (MGB2) are 2 related genes of the uteroglobin gene family that are overexpressed in breast tissue and metastatic lymph nodes from patients with breast cancer [4,47,48]. After careful analysis of the literature on micrometastasis detection in sentinel lymph nodes, we selected the MGB2 gene as one of the most specific PCR markers to detect potential malignant breast cell invasion in our cryopreserved ovarian tissue [1,4,20,30,34].…”

Section: Introductionmentioning

confidence: 99%

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Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study

Luyckx

Durant

Camboni

et al. 2013

J Assist Reprod Genet

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Section: Resultsmentioning

confidence: 76%

Section: Quantitative Pcr Analysesmentioning

confidence: 99%

Section: Quantitative Pcr Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study

Luyckx

Durant

Camboni

et al. 2013

J Assist Reprod Genet

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“…Mammaglobin-1 and -2 were amplified in additional 30.1 and 17.8% of the H&E-negative nodes. In an interim analysis of a multi-institutional study of multimarker RT -PCR of H&E-negative lymph nodes (Gillanders et al, 2004), a correlation between PCR positivity and other well-established prognostic markers including histological grade and St Gallen risk category was reported. This study also showed mammaglobin to be the most informative marker in their multimarker panel.…”

Section: Discussionmentioning

confidence: 99%

Multimarker RT–PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients

et al. 2006

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The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase -polymerase chain reaction (RT-PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT -PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT -PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT -PCR. We conclude that a multimarker RT -PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation. Although up to 80% of breast cancer patients are identified at an early stage when disease is apparently localised, 30 -35% of nodenegative patients will develop clinically detectable distant metastases within 5 years of treatment of the primary breast carcinoma and ultimately suffer tumour-related mortality (Nemoto et al, 1980). Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. It is usually performed with a single haematoxilyn and eosin (H&E)-stained section through the examined node and therefore small metastases can go undetected. In a landmark study conducted by the International (Ludwig) Breast Cancer Group (International (Ludwig) Breast Cancer Study Group, 1990), serial sectioning of axillary lymph nodes judged to be disease free after routine histological examination revealed micrometastases in 83 (9%) of 921 breast cancer patients. These patients had a poorer disease-free (P ¼ 0.003) and overall (P ¼ 0.002) survival after 5 years' median follow-up than did patients whose nodes remained negative on serial sectioning. A later study performed by the same group (Cote et al, 1999) examined lymph nodes negative for metastases on routine histology from 736 patients by serial sectioning and by immunohistochemistry (IHC) with two anticytokeratins AE-1 and CAM 5.2. Occult nodal metastases were detected by serial sectioning and H&E in 7% of the patients and by IHC in 20%. After median follow-up of 12 years, occult metastases, detected by either method, were associated with significantly poor disease-free and overall survival in pos...

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Intraoperative assessment of sentinel lymph nodes in breast cancer

Layfield¹,

Agrawal

Roché

et al. 2010

British Journal of Surgery

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Background: Sentinel lymph node biopsy (SLNB) reduces the morbidity of axillary clearance and is the standard of care for patients with clinically node-negative breast cancer. The ability to analyse the sentinel node during surgery enables a decision to be made whether to proceed to full axillary clearance during primary surgery, thus avoiding a second procedure in node-positive patients.Methods: Current evidence for intraoperative sentinel node analysis following SLNB in breast cancer was reviewed and evaluated, based on articles obtained from a MEDLINE search using the terms 'sentinel node', 'intra-operative' and 'breast cancer'.Results and conclusion: Current methods for evaluating the sentinel node during surgery include cytological and histological techniques. Newer quantitative molecular assays have been the subject of much recent clinical research. Pathological techniques of intraoperative SLNB analysis such as touch imprint cytology and frozen section have a high specificity, but a lower and more variably reported sensitivity. Molecular techniques are potentially able to sample a greater proportion of the sentinel node, and could have higher sensitivity.

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Molecular Detection of Micrometastatic Breast Cancer in Histopathology-Negative Axillary Lymph Nodes Correlates With Traditional Predictors of Prognosis

Cited by 104 publications

References 32 publications

Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study

Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study

Multimarker RT–PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients

Intraoperative assessment of sentinel lymph nodes in breast cancer

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