The detection of minimal numbers of contaminating epithelial tumor cells in blood or bone marrow: Use, limitations and future of RNA-based methods

Lambrechts, A. C.; Veer, Laura J. van ’t; Rodenhuis, S.

doi:10.1023/a:1008445604263

Cited by 56 publications

(43 citation statements)

References 53 publications

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“…Although some studies emphasized the high sensitivity of TG mRNA testing, 8 -11 we suggest that more than a single marker gene be used, including specific assays such as TPO and TSHR mRNA, to reduce the number of false positive results that are generally associated with RT-PCR-based test systems. 33 In conclusion, our findings demonstrate that serum TG assay after TSH stimulation remains the most accurate test for monitoring patients operated for DTC. Quantitative analysis of a panel of thyroid-specific transcripts in peripheral blood may be useful, as a complement to serum TG assay, in the follow-up of DTC patients.…”

Section: Discussionsupporting

confidence: 51%

Evaluation of circulating thyroid‐specific transcripts as markers of thyroid cancer relapse

Barzon¹,

Boscaro²,

Pacenti³

et al. 2004

Intl Journal of Cancer

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Circulating thyroid-specific transcripts have been suggested as potential molecular markers of residual or recurrent thyroid cancer. We assessed the accuracy of real-time RT-PCR-based detection of a panel of thyroid-specific markers, including TG, TPO, TSHR, NIS and PDS, in comparison with serum TG measurements in a series of 55 patients operated for differentiated thyroid cancer (DTC). Serum TG levels were higher in patients with residual thyroid tissue or metastatic cancer than in disease-free patients during thyroid hormone suppressive therapy (THST) and after stimulation with rhTSH (P < 0.05). Recombinant hTSH increased serum TG values in patients with tumor relapse (P < 0.05), but not in disease-free patients. This assay showed high specificity and good sensitivity in detecting tumor relapse (accuracy under THST ‫؍‬ 81.4%; after rhTSH stimulation ‫؍‬ 90.9%). TPO and TSHR mRNA, either under THST or after rhTSH, showed a significant correlation with disease status for molecular assays. Qualitative analysis of baseline and stimulated TG, NIS and PDS mRNA showed high sensitivity but low specificity in the prediction of thyroid cancer recurrence or metastases (accuracy under THST ‫؍‬ 51%, 43% and 54%, respectively), whereas TPO and TSHR mRNA assays had higher specificity but low sensitivity, with accuracy under THST of 67% and 61%, respectively, that improved when these tests were combined. Differentiated thyroid carcinoma (DTC), which comprises papillary and follicular thyroid cancer, is the most common thyroid malignancy and accounts for 1% of all human cancers. Its incidence is increasing in many countries, likely due to exposure of the population to thyroid radiation. Differentiated thyroid carcinoma generally has an excellent prognosis after treatment with total or near-total thyroidectomy followed by 131-iodine ( 131 I) ablation. However, about 20 -40% of patients with DTC may develop recurrences or metastases even after successful initial therapy. A lifelong follow-up is therefore recommended for early discovery of residual or recurrent disease.Management protocols include periodic radioiodine whole body scanning (WBS) and measurements of serum thyroglobulin (TG) protein by immunoassay. 1 Thyroid hormone withdrawal or, more recently, administration of recombinant human thyroid-stimulating hormone (rhTSH) is required to produce the TSH stimulation needed to achieve maximal accuracy for these diagnostic tests. In comparison with thyroid hormone withdrawal, stimulation with rhTSH avoids side-effects associated with hypothyroidism. Serum TG measurement shows some advantages over WBS in the follow-up of DTC, having a higher sensitivity and no false positive results after TSH stimulation, 2,3 besides avoidance of exposure to radiation, lower costs and wide availability. A major disadvantage of this test, however, is the presence of interfering anti-TG antibodies in 10 -20% of patients.In the search of a more accurate test for diagnosis of residual or recurrent DTC, the possibility to detect transcripts from cir...

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Section: Discussionsupporting

confidence: 51%

Evaluation of circulating thyroid‐specific transcripts as markers of thyroid cancer relapse

Barzon¹,

Boscaro²,

Pacenti³

et al. 2004

Intl Journal of Cancer

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“…In contrast to hematological malignancies, solid tumours rarely present specific diagnostic genetic changes. In order to overcome this limitation, tissue-specific markers have been evaluated as potential molecular targets for the detection of occult tumour cells [11][12][13]. Cytokeratin transcripts (CK19 and CK20) have been widely used in the detection of occult breast cells, but we and others have reported low specificity of these assays [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Detection of human mammaglobin mRNA in serial peripheral blood samples from patients with non-metastatic breast cancer is not predictive of disease recurrence

Marques

Teixeira

Diamond

et al. 2008

Breast Cancer Res Treat

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International audienceHuman mammaglobin (hMAM) mRNA is a sensitive and specific marker of breast cancer cells. We evaluated if hMAM mRNA detection in serial peripheral blood samples from non-metastatic breast cancer patients predicts for disease recurrence. Patients scheduled for adjuvant or neoadjuvant chemotherapy were eligible. Serial blood samples were collected up to 5 years, the first before (neo)adjuvant chemotherapy. hMAM gene expression was analysed by RT-PCR. Specificity was evaluated in blood samples from healthy volunteers. A total of 321 patients were included. The incidence of pre-chemotherapy hMAM-positive samples was similar in patients who latter experienced cancer recurrence (22.4%) and those who remained disease-free (17.9%; = 0.46). Similarly, the mean number of positive follow-up samples was similar in both groups (0.15 ± 0.22 and 0.13 ± 013; = 0.29). Furthermore, there was no difference in disease-free (= 0.63) or overall survival (= 0.57) in patients with and without positive baseline samples or between patients whose follow-up samples were always hMAM negative and those with at least one positive sample. Multivariate survival analysis confirmed that hMAM mRNA detection before or after (neo)adjuvant chemotherapy was not predictive of recurrence. There is no evidence that hMAM mRNA detection at diagnosis or during follow-up predicts for breast cancer recurrence

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“…We have recently shown that the tendency for hematogenous spread can already be shown in small tumours, using messenger-RNA (mRNA) expression profiling . In addition, we and others have developed immunological and RNA-based methods to detect circulating tumour cells in blood, bone marrow and other nonbreast tissues (Lambrechts et al, 1998). There is evidence that the presence of epithelial cells in the bone marrow of patients with early breast cancer correlates with prognosis (Braun et al, 2000).…”

mentioning

confidence: 99%

“…There is evidence that the presence of epithelial cells in the bone marrow of patients with early breast cancer correlates with prognosis (Braun et al, 2000). Antibody-based methods to detect these occult tumour cells have, however, not gained widespread clinical use because of significant numbers of false-positive results (Lambrechts et al, 1998(Lambrechts et al, , 1999.…”

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confidence: 99%

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

et al. 2003

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We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P ¼ 0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P ¼ 0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral blood.

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The detection of minimal numbers of contaminating epithelial tumor cells in blood or bone marrow: Use, limitations and future of RNA-based methods

Cited by 56 publications

References 53 publications

Evaluation of circulating thyroid‐specific transcripts as markers of thyroid cancer relapse

Evaluation of circulating thyroid‐specific transcripts as markers of thyroid cancer relapse

Detection of human mammaglobin mRNA in serial peripheral blood samples from patients with non-metastatic breast cancer is not predictive of disease recurrence

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

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