Presence of erbB2 mRNA in the plasma of breast cancer patients is associated with circulating tumor cells and negative estrogen and progesterone receptor status
Several studies have demonstrated that tumor cell-derived RNA is presented in the plasma from breast cancer patients. However, no studies have focused on the detection of plasma erbB2 mRNA in breast cancer. In this study the expression of erbB2 mRNA in the plasma was analyzed in 106 breast cancer patients and 50 healthy subjects by using a nested RT-PCR strategy, and the circulating tumor cells were also detected by using a nested RT-PCR for detection of mammaglobin transcripts in the peripheral blood. Plasma erbB2 mRNA was detectable in 46 (43.3%) breast cancer patients, whereas only 5 normal subjects (10%) were positive in the control group (p = 0.001). The presence of erbB2 mRNA in the plasma was not associated with menopausal status, erbB2 expression in primary tumor tissues, tumor size, histological grade, Ki-67 expression or lymph node involvement, but it exhibited a trend for correlation with increasing tumor stages (p = 0.085), and the presence of erbB2 mRNA in the plasma was significantly associated with negative estrogen receptor (ER) and progesterone receptor (PR) status of the primary tumors (p = 0.031 and 0.026, respectively). Furthermore, in a small subset of 36 breast cancer patients we found the presence of plasma erbB2 mRNA was significantly correlated with the occurrence of circulating tumor cells (p = 0.01). Our study suggests that breast cancer patients with the presence of erbB2 mRNA in the plasma may have a high malignancy or an aggressive phenotype, and frequently detecting plasma erbB2 mRNA may provide a novel approach for monitoring breast cancer progression or response to treatment.
Keywordsbreast cancer erbB2 mRNA plasma
Unable to display preview. Download preview PDF.
- 2.Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 352(9132): 930–942, 1998Google Scholar
- 3.Rennstam K, Ahlstedt-Soini M, Baldetorp B, Bendahl PO, Borg A, Karhu R, Tanner M, Tirkkonen M, Isola J: 2003 Patterns of chromosomal imbalances defines subgroups of breast cancer with distinct clinical features and prognosis. A study of 305 tumors by comparative genomic hybridizationCancer Res 63(24): 8861–8868PubMedGoogle Scholar
- 6.Beau-Faller M, Gaub MP, Schneider A, Ducrocq X, Massard G, Gasser B, Chenard MP, Kessler R, Anker P, Stroun M, Weitzenblum E, Pauli G, Wihlm JM, Quoix E, Oudet P,: 2003 Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer patientsInt J Cancer 105(3): 361–370CrossRefPubMedGoogle Scholar
- 15.Hartmann LC, Ingle JN, Wold LE, Farr GH, Jr, Grill JP, Su JQ, Maihle NJ, Krook JE, Witzig TE, Roche PC: 1994 Prognostic value of c-erbB2 overexpression in axillary lymph node positive breast cancer. Results from a randomized adjuvant treatment protocolCancer 74(11): 2956–2963CrossRefPubMedGoogle Scholar
- 16.Joensuu H, Isola J, Lundin M, Salminen T, Holli K, Kataja V, Pylkkanen L, Turpeenniemi-Hujanen T, von Smitten K, Lundin J: 2003 Amplification of erbB2 and erbB2 expression are superior to estrogen receptor status as risk factors for distant recurrence in pT1N0M0 breast cancer: a nationwide population-based studyClin Cancer Res 9(3): 923–930PubMedGoogle Scholar
- 19.Grunewald K, Haun M, Urbanek M, Fiegl M, Muller-Holzner E, Gunsilius E, Dunser M, Marth C, Gastl G: 2000 Mammaglobin gene expression: a superior marker of breast cancer cells in peripheral blood in comparison to epidermal-growth-factor receptor and cytokeratin-19Lab Invest 80(7): 1071–1077PubMedGoogle Scholar
- 26.Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, Beitsch P, Khan A, Euhus D, Osborne C, Frenkel E, Hoover S, Leitch M, Clifford E, Vitetta E, Morrison L, Herlyn D, Terstappen LW, Fleming T, Fehm T, Tucker T, Lane N, Wang J, Uhr J: 2004 HER-2 gene amplification can be acquired as breast cancer progressesProc Natl Acad Sci U S A 101(25): 9393–9398CrossRefPubMedGoogle Scholar
- 27.Meng S, Tripathy D, Frenkel EP, Shete S, Naftalis EZ, Huth JF, Beitsch PD, Leitch M, Hoover S, Euhus D, Haley B, Morrison L, Fleming TP, Herlyn D, Terstappen LW, Fehm T, Tucker TF, Lane N, Wang J, Uhr JW: 2004 Circulating tumor cells in patients with breast cancer dormancyClin Cancer Res 10(24): 8152–8162CrossRefPubMedGoogle Scholar
- 28.Stathopoulou A, Vlachonikolis I, Mavroudis D, Perraki M, Kouroussis C, Apostolaki S, Malamos N, Kakolyris S, Kotsakis A, Xenidis N, Reppa D, Georgoulias V: 2002 Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significanceJ Clin Oncol 20(16): 3404–3412CrossRefPubMedGoogle Scholar
- 29.Xenidis N, Vlachonikolis I, Mavroudis D, Perraki M, Stathopoulou A, Malamos N, Kouroussis C, Kakolyris S, Apostolaki S, Vardakis N, Lianidou E, Georgoulias V: 2003 Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancerAnn Oncol 14(6): 849–855CrossRefPubMedGoogle Scholar