Sensitive detection of occult breast cancer by the reverse-transcriptase polymerase chain reaction

Detection of occult carcinoma in patients with breast cancer may aid the establishment of prognosis and development of new therapeutic approaches. To improve on existing methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for keratin 19 (K19) tran...

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Vydané v:Journal of clinical oncology Ročník 12; číslo 3; s. 475
Hlavní autori: Datta, Y H, Adams, P T, Drobyski, W R, Ethier, S P, Terry, V H, Roth, M S
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.03.1994
Predmet:
Base Sequence
Biomarkers, Tumor - analysis
Bone Marrow - metabolism
Breast Neoplasms - diagnosis
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Female
Humans
Keratins - analysis
Keratins - genetics
Molecular Sequence Data
Neoplasm Metastasis - diagnosis
Polymerase Chain Reaction - methods
RNA, Messenger - analysis
RNA, Neoplasm - analysis
RNA-Directed DNA Polymerase
Sensitivity and Specificity
ISSN:0732-183X
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Shrnutí:Detection of occult carcinoma in patients with breast cancer may aid the establishment of prognosis and development of new therapeutic approaches. To improve on existing methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for keratin 19 (K19) transcripts to identify mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. Peripheral-blood or bone marrow samples obtained from 34 patients with stages I to IV breast cancer and 39 control subjects without breast cancer were screened for K19 mRNA by nested primer PCR. In reconstitution experiments, K19 RT-PCR reliably detected 10 mammary carcinoma cells in 1 million normal peripheral-blood mononuclear (PBMN) cells. Four of 19 patients with stage IV breast cancer had detectable K19 transcript in peripheral blood. Five of six patients with histologically negative bone marrow biopsies following preablative chemotherapy and before autologous bone marrow transplant (BMT) were positive by this assay. Stem-cell apheresis harvests obtained from one of these patients and three additional patients immediately before BMT were all K19-negative. K19 RT-PCR analysis of CSF from a breast cancer patient with known carcinomatous meningitis was also positive. Thirty-eight of 39 non-breast cancer patients had negative K19 RT-PCR assays. The one exception was a patient with chronic myelogenous leukemia. RT-PCR of K19 is a sensitive, specific, and rapid method for detection of occult mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. The presence of residual breast cancer cells in histologically normal bone marrow aspirates but not in stem-cell apheresis harvests is a frequent finding. This assay may be useful in diagnosing metastatic disease, as well as in monitoring the effectiveness of systemic therapy.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0732-183X
DOI:10.1200/jco.1994.12.3.475