Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple-marker RT-PCR

Bostick, Peter J.; Huynh, Kelly; Sarantou, Terry; Turner, Roderick R.; Qi, Karen; Giuliano, Armando E.; Hoon, Dave S.B.

doi:10.1002/(sici)1097-0215(19981218)79:6<645::aid-ijc16>3.0.co;2-r

Cited by 71 publications

(25 citation statements)

References 41 publications

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“…The second problem is how to determine the appropriate extent of lymph node dissection in cases where SNs do contain metastases. Several investigators have reported using ultrasensitive molecular techniques for RT -PCR detection of micrometastasis in blood, bone marrow, and lymph nodes (Rosen et al, 1981;Ioguchi et al, 1994;Brown et al, 1995;Mori et al, 1995;Bostick et al, 1998;Takakura et al, 1998). This method has increased the detection rate for occult metastases as a result of amplification of mRNA tumour markers or epithelial markers and it has been suggested that patients exhibiting a positive band for these mRNAs in lymph nodes had a significantly worse prognosis than those who were RT -PCR-negative (Natsugoe et al, 1998;Cai et al, 1999;Noura et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Micrometastases in sentinel nodes of gastric cancer

Ajisaka

Miwa

2003

Br J Cancer

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The sentinel node (SN) is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of the remaining nodes in the basin. We succeeded in detecting SNs of clinically early gastric cancers by intraoperative injection of a blue dye around the tumour. In the study presented here, multiple-marker reverse transcriptionpolymerase chain reaction (RT -PCR) was used to detect micrometastases in SNs and results were compared with those obtained with conventional histology. Expressions of cytokeratin-18 (CK-18), carcinoembryonic antigen (CEA), human telomerase reverse transcriptase (hTRT) and MUC-1 in SNs were determined by RT -PCR and Southern blot assay. Of the 213 SNs obtained from 35 cases of gastric cancer, eight nodes (3.8%) from five patients contained metastases that could be identified by conventional histology. However, CK-18 mRNA was expressed in 15 (7.0%), CEA in 12 (5.6%), hTRT in 10 (4.7%), and MUC-1 in 12 (5.6%) nodes, with at least one mRNA marker expressed in 25 nodes (11.7%) obtained from six patients. In the five patients with nodal metastases identified by conventional histology, two had metastases in both SNs and non-SNs. And, in the 30 patients without nodal metastases identified by conventional histology, one patient with micrometastases in the SNs identified by RT -PCR and Southern blot assay also had metastases in non-SNs as identified by serial sectioning and immunostaining of CK-18. All additional metastases were detected in non-SNs located in the same lymphatic basin as the previously detected SNs. This suggests that lymph node dissection of early-stage gastric cancer in the lymphatic basin may be mandatory even for patients without histologically detectable metastases in SNs. British Journal of Cancer (2003) Lymph node metastasis is one of the most important determinants of whether minimally invasive surgery for early gastric cancer is appropriate, since lymph node dissection generally is considered unnecessary for early gastric cancer without nodal metastasis. Endoscopic mucosal resection or minimally invasive surgery without lymphadenectomy has recently been advocated for early gastric cancer without nodal metastasis. Predicting the absence of nodal metastasis is usually based on indirect evidence, by comparing the primary tumour in a particular case with those in other cases (Makuuchi et al, 1999). We succeeded in identifying sentinel nodes (SNs) in gastric cancer by intraoperative injection of blue dye around the tumour (Miwa et al, 2003). The SN is the first lymph node in the lymphatic basin to be affected by metastasis from the primary tumour and is used to predict the status of lymph nodes in the rest of the lymphatic basin (Morton et al, 1992). Metastases in the SNs are determined by intraoperative pathology, but if there is a discrepancy between the intraoperative diagnosis and postoperative diagnosis detailed examination results, a definitive operation cannot be performed only on the basis of a sentinel node biop...

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Section: Discussionmentioning

confidence: 99%

Micrometastases in sentinel nodes of gastric cancer

Ajisaka

Miwa

2003

Br J Cancer

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“…RT-PCR has proved to be a highly sensitive method for detecting cancer cells in the regional lymph nodes or SLNs of breast cancer patients (15,16,(34)(35)(36)(37)(38). Since no ideal breast cancer marker has been identified yet, it can be hypothesized that a multimarker RT-PCR panel would increase the sensitivity and specificity of this assay (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

“…Since no ideal breast cancer marker has been identified yet, it can be hypothesized that a multimarker RT-PCR panel would increase the sensitivity and specificity of this assay (35)(36)(37). Several markers have already been investigated (34)(35)(36)(37). CK20 is an epithelial marker which is not expressed in normal lymph nodes (37).…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge the results of five studies on RT-PCR examination performed on SLNs of breast cancer patients have been published to date (34)(35)(36)(37)(38). In four of these studies multimarker assays were used (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

“…In four of these studies multimarker assays were used (35)(36)(37)(38). CK20 was used only in one study (37).…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemistry and Reverse Transcriptase Polymerase Chain Reaction on Sentinel Lymph Nodes can Improve the Accuracy of Nodal Staging in Breast Cancer Patients

et al. 2001

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In this study the nodal staging sensitivity of sentinel lymph node biopsy (SLNB) with detailed pathological and molecular biological examination has been investigated and compared to that of axillary lymph node dissection (ALND) with routine histological evaluation. Sentinel lymph nodes (SLNs) were removed by the dual-agent injection technique in 68 patients with primary, clinically node-negative breast cancer. Forty-seven patients had negative SLNs according to hematoxylin and eosin (H&E) staining. These H&E-negative SLNs were serially sectioned and examined at 250 µm levels by anticytokeratin immunohistochemistry (IHC). In 14 patients the SLNs were also investigated by cytokeratin 20 (CK20) reverse transcriptase polymerase chain reaction (RT-PCR). SLNB with IHC increased the node-positive rate by 26% (by 40% in tumors less than or equal to 2 cm in size (pT1) and by 9% in tumors more than 2 cm but less than or equal to 5 cm in size (

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Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes

et al. 2001

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The identification of specific tumor mRNA markers by reverse transcription‐polymerase chain reaction might be a valuable diagnostic adjunct for the detection of breast cancer metastases in axillary sentinel lymph nodes (SLNs). In this study we have compared the diagnostic accuracy of an extensive histopathologic examination of 146 SLNs from 123 breast carcinoma patients with that of the evaluation of 5 mRNA markers. When analyzed individually, none of the different markers attained a sensitivity higher than 77.8%, and the general concordance with the histopathologic findings ranged from 78.8 to 83.6%. In a multiple‐marker assay, taking into account the expression of at least 1 of the 5 tumor markers, the sensitivity of the test rose to 95.6%, with a specificity of 66.3% and a general concordance with the histopathologic status of 75.3%. Finally, when at least 2 of 3 markers (maspin, cytokeratin 19 and mammaglobin 1) were expressed, the concordance with either SLN or axillary lymph node status was highest (88.4% and 84.6%, respectively). The high prevalence of positive reverse transcription‐polymerase chain reaction assays in histologically uninvolved SLNs, however, may hamper extensive application of these techniques in the clinical setting. © 2001 Wiley‐Liss, Inc.

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Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple-marker RT-PCR

Cited by 71 publications

References 41 publications

Micrometastases in sentinel nodes of gastric cancer

Micrometastases in sentinel nodes of gastric cancer

Immunohistochemistry and Reverse Transcriptase Polymerase Chain Reaction on Sentinel Lymph Nodes can Improve the Accuracy of Nodal Staging in Breast Cancer Patients

Reverse transcription-polymerase chain reaction assay for multiple mRNA markers in the detection of breast cancer metastases in sentinel lymph nodes

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