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

Putative markers for the detection of breast carcinoma cells in blood

“…Under similar experimental conditions, we have demonstrated background expression of MUCI in the peripheral blood of 21 of 23 healthy human female volunteers. In support of these findings, Hoon et al (1995) Figure 1C MUCI expression in seven of eight normal donor peripheral blood leucocytes and four normal lymph nodes. Our results also raise serious doubts about the value of using CD44 (exons 8-11) mRNA to detect circulating tumour cells because of the frequency with which it is found in normal peripheral blood.…”

Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

“…However, data from studies assessing the detection of disease in colon and lung cancer have raised questions with regard to the tissue specificity of these markers (Adams et al, 1995;Burchill et al, 1995;Hoon et al, 1995;Krismann et al, 1995;Denis et al, 1997;Dingemans et al, 1997;Eltahir et al, 1998) CEA gene expression must be regarded with caution as a tumour specific marker, as it has been detected by nested RT-PCR in normal tissues. Jonas et al (1996) found 23% of controls without cancer had evidence of CEA expression in peripheral blood, which the authors propose may be due to venepuncture-induced skin contamination.…”

“…Whilst lacking specific markers expressed by breast cancer cells a number of research groups have used cytokeratins 18 and 19, epithelial mucin (MUC1), carcinoembryonic antigen (CEA), CD 44 and maspin as transcript markers for the detection of submicroscopic metastases in lymph nodes, bone marrow or peripheral whole blood by reverse transcription PCR (RT-PCR) (Matsumura and Tarin, 1992;Datta et al, 1994;Gerhard et al, 1994;Noguchi et al, 1994Noguchi et al, , 1996aNoguchi et al, , 1996bSchoenfeld et al, 1994Schoenfeld et al, , 1996Schoenfeld et al, , 1997Brown et al, 1995;Mori et al, 1995;Gunn et al, 1996;Luppi et al, 1996;Yun et al, 1997;Eltahir et al, 1998;Lockett et al, 1998). However, there appears to be conflicting data regarding the specificity of some of these cell type specific markers in particular MUC-1 (Noguchi et al, 1994;Hoon et al, 1995), CD44 (Matsumura and Tarin, 1992;Eltahir et al, 1998) and K19 (Traweek et al, 1993;Schoenfeld et al, 1994Schoenfeld et al, , 1996Burchill et al, 1995;Krismann et al, 1995;Gunn et al, 1996;Dingemans et al, 1997;Yun et al, 1997;Eltahir et al, 1998). Maspin expression has been previously reported as being a specific marker for breast cancer (Luppi et al, 1996); however, there have been no larger confirmatory studies to assess the accuracy and reproducibility of these findings.…”

Low specificity of PGP9.5 expression for detection of micrometastatic neuroblastoma

“…A number of preliminary studies have indicated that PCR-based analysis of neuroblastoma-associated gene transcripts might be useful in improving the detection of micrometastatic disease either British Journal of Cancer (1997) 75 (12), [1779][1780][1781] Neuroblastoma-specific gene expression 1781 at diagnosis or following therapy (Naito et al, 1991;Burchill et al, 1994Burchill et al, , 1995Miyajima et al, 1995 (Smith et al, 1995;Krismann et al, 1995;Hoon et al, 1995). Although the detection of PGP9.5 expression in normal tissues could presumably be reduced or eliminated by using only a single round of PCR, or by reducing the number of PCR cycles, such manipulations would, of necessity, reduce the sensitivity with which the target tumour cells could also be detected.…”

“…For example, Krismann et al (1995) have recently reported a significant number of false-positive results for RT-PCR analysis of cytokeratin 19 mRNA expression in samples of normal peripheral blood, although this gene has been proposed for detection of occult breast and prostate cancer metastases (Wood et al, 1993Datta et al, 1994. Likewise, although prostate-specific antigen mRNA and MUC1 mRNA have been used for PCR detection of prostate and breast micrometastases, respectively (Noguchi et al, 1994;Ghossein et al, 1995), recent reports have demonstrated expression of prostatespecific antigen in cells of non-prostate origin (Smith et al, 1995), and MUCI expression in non-neoplastic lymph nodes (Hoon et al, 1995). In view of these findings, we have employed a highly sensitive 'nested' RT-PCR assay in order to evaluate the expression of tyrosine hydroxylase and PGP9.5 in a range of normal blood and bone marrow samples.…”