The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction

Noguchi, Shinzaburo; Aihara, Tomohiko; Nakamori, Shoji; Motomura, Kazuyoshi; Inaji, Hideo; Imaoka, Shingi; Koyama, Hiroki

doi:10.1002/1097-0142(19940901)74:5<1595::aid-cncr2820740516>3.0.co;2-l

Cited by 218 publications

(138 citation statements)

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“…Several reports have indicated that the detection of micrometastases using reverse transcriptase -polymerase chain reaction (RT -PCR) assay may be clinically important (Noguchi et al, 1994(Noguchi et al, , 1996Schoenheld et al, 1994;Mori et al, 1995Mori et al, , 1998Masuda et al, 2000;Manzotti et al, 2001). Moreover, screening for metastatic disease in axillary lymph nodes by RT -PCR amplification has been shown to be more sensitive and cost effective than serial sectioning and immunohistochemical staining (Lockett et al, 1998).…”

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confidence: 99%

Quantitative evaluation of metastases in axillary lymph nodes of breast cancer

et al. 2003

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We have established a highly sensitive and quantitative reverse transcriptase -polymerase chain reaction (RT -PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT -PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT -PCR assay were 4.5, 5.9 and 13.1%, respectively. RT -PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (Po0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (Po0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT -PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT -PCR assay may be useful to assess the entire axillary burden of breast cancer patients.

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Quantitative evaluation of metastases in axillary lymph nodes of breast cancer

et al. 2003

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“…Strategies for reducing microscopic misdiagnosis that have been tested include using immunohistochemical techniques to highlight metastases (Wells et al, 1984). More recently, a technique using reverse transcriptase-polymerase chain reaction (RT-PCR) to detect expression of tumour-associated antigen mRNA extracted from axillary nodes has been tested as an alternative to histopathological examination (Noguchi et al, 1994).However, using either serial sectioning or immunohistochemical detection in isolation ignores the alternative source of error in diagnosis. For example, in a Ludwig Breast Cancer Study Group examination of lymph nodes from 921 patients using a laborious serial sectioning procedure examining 36 sections from each block, only 9% of patients were found to have metastases [International (Ludwig) Breast Cancer Study Group, 1990].…”

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Occult axillary node metastases in breast cancer: their detection and prognostic significance

McGuckin

Cummings²,

Walsh³

et al. 1996

Br J Cancer

227

142

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Summary Although the presence of axillary node metastases in breast cancer is a key prognostic indicator and may influence treatment decisions, a significant proportion of patients diagnosed as axillary node negative (ANN) using standard histopathological techniques may have occult nodal metastases (OMs). A combination of limited step-sectioning (4 x 100 /im intervals) and immunohistochemical staining (with cytokeratin (MNF.116) and MUCI (BC2) antibodies) was used to detect OM in a retrospective series of 208 ANN patients. OMs were found in 53 patients (25%), and both step-sectioning and immunohistochemical detection significantly improved detection (P<0.05). Detection using BC2 (25%) was superior to MNF. 116 (18%) and haematoxylin and eosin (H&E) (8%). OMs were found in 51 patients using only the first and deepest sectioning levels and BC2 staining. OMs were more frequently found in lobular (38%) than ductal carcinoma (25%), and more frequently in women less than 50 years (41%) than in older women (19%). Univariate overall and disease-free survival analyses showed that the presence, size and number of OM had prognostic significance as did tumour size (disease-free only) and histological and nuclear grade (P>0.05). Cox multivariate proportional hazard regression analyses showed that the presence and increasing size of OMs were significantly associated with poorer disease-free survival, independently of other prognostic factors (P>0.05). However there was not a significant independent association of the presence of occult metastases with overall survival (P =0.11). These findings have important implications with regard to selection of ANN patients for adjuvant therapy.Keywords: breast cancer; prognosis; occult metastases; detection; mucin Several large clinical trials have illustrated the survival benefits of adjuvant endocrine or chemotherapeutic treatments in patients with axillary node-negative (ANN) breast cancer (Fisher and Redmond, 1992;Stewart, 1992 (Nemoto et al., 1980), yet is has been recognised for some time that a significant proportion of patients diagnosed as node negative using standard histopathological techniques may in fact have nodal metastases. However, the proportion of ANN patients with these occult metastases, the best practical way of detecting them, and the prognostic significance of these metastases remain unclear. There are two main sources of error in the current histopathological examination of axillary lymph nodes for the detection of metastases. The first involves sampling error attributable to the sectioning procedure and is related to the size of the node, the orientation of the node in the sectioning block, the size and location of any metastases, and the number of sections examined (Wilkinson and Hause, 1974). The second involves microscopic misdiagnosis of sectioned metastases, which is related to the size and location of the metastases and the morphology of the lesions and surrounding nodal tissue.Strategies for reducing sectioning error that have been tested include macroscop...

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“…RT-PCR of keratin 19 (K19) transcripts has been used to detect occult breast cancer in peripheral blood and bone marrow (Datta et al, 1994). RT-PCR of MUCI mRNA, which encodes a core protein of polymorphic epithelial mucin, has been employed for the detection of micrometastases in axillary lymph nodes of breast cancer patients (Noguchi et al, 1994). In this study, we used RT-PCR amplification of PSA mRNA in peripheral blood of women with different stages of breast cancer.…”

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confidence: 99%