Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients.

Bostick, Peter J.; Chatterjee, Sumana; Dorcas, D. J.; Huynh, Kelly; Giuliano, Armando E.; Côté, Richard J.; Hoon, Dave S. B.

doi:10.1200/jco.1998.16.8.2632

Cited by 320 publications

(215 citation statements)

References 34 publications

Supporting

Mentioning

200

Contrasting

Unclassified

Order By: Relevance

“…So far no expression of HMGI-C in the peripheral blood of healthy controls could be found, which is of advantage, since the specificity of other RT -PCR assays in breast cancer, such as RT -PCR for cytokeratin 19, had to be questioned due to an expression in healthy controls (Bostick et al, 1998;Slade et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

et al. 2003

View full text Add to dashboard Cite

HMGI-C belongs to the high-mobility-group-protein (HMG) family of architectural transcription factors and considerable interest has recently been shown in its expression in neoplastic tissues and apparent involvement in tumorigenesis. We could previously demonstrate an expression of HMGI-C mRNA in the peripheral blood of breast cancer patients for the first time. In this prospective study, we evaluated the independent prognostic power of HMGI-C mRNA expression in the peripheral blood of an unselected cohort of 69 patients with metastatic breast cancer using a hemi-nested reverse transcriptase polymerase chain reaction (RT -PCR) followed by sequence analysis of the resulting PCR products. Multivariate analysis was performed using the Cox regression model. HMGI-C mRNA was detected in peripheral blood from 21 out of 69 (30%) patients with metastatic breast cancer. Median survival was 15.9 months in patients expressing HMGI-C, while in the group of patients without HMGI-C expression the median survival had not been reached yet after a median follow-up of 24.7 months and 85.4% were still alive in this group. Disease-specific survival was significantly worse for patients positive for HMGI-C in comparison to those not expressing HMGI-C (P ¼ 0.0001). In a multivariate regression analysis, HMGI-C remained an independent prognostic factor for overall survival (P ¼ 0.001) besides oestrogen receptor status (P ¼ 0.024) and presence of metastases in liver and lungs (P ¼ 0.029). HMGI-C expression in the peripheral blood of patients with metastatic breast cancer is a powerful independent indicator for poor overall survival and this is the first study to demonstrate its prognostic relevance in univariate and multivariate analysis.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

et al. 2003

View full text Add to dashboard Cite

show abstract

“…17 However, high rates of false positive control samples using tissue specific markers, including CK19, have been reported previously. [35][36][37][38] This is often due to illegitimate transcription. 39 It is, thus, not possible to discriminate between low levels of illegitimate expression in normal cells from high levels of expression in a few tumour cells.…”

Section: Discussionmentioning

confidence: 99%

HPV16‐E6 mRNA is superior to cytokeratin 19 mRNA as a molecular marker for the detection of disseminated tumour cells in sentinel lymph nodes of patients with cervical cancer by quantitative reverse‐transcription PCR

Häfner

Gajda

Altgassen

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

About 10-15% of patients with cervical cancer suffer from recurrence despite histologically negative lymph nodes (pN0). Occult micrometastases or small tumour cell clusters may contribute to disease outcome. The aim of this study was to compare at the RNA level 2 known tumour-associated genes, HPV16-E6 and cytokeratin 19 (CK19), as molecular markers for the detection of disseminated tumour cells. Real-time reverse transcription PCR technology was used to quantify gene expression in histologically positive and negative sentinel lymph nodes (SLN) from 70 patients with cervical cancer. Lymph nodes from noncancer patients were used as controls. Calculated copy numbers were normalised to the geometric average of the most stable housekeeping genes. We observed a good correlation (R 5 0.915) between the expression of both markers in SLN with histologically confirmed metastases. However, marker gene expression differed considerably in histologically negative nodes: CK19 transcripts were detected in 90 of 112 SLN (80.4%), whereas only 38 nodes (33.9%) were positive for HPV16 E6 mRNA. In particular, 62 of 74 SLN, which were negative by histology, and HPV16 E6 mRNA expressed CK19 mRNA. Moreover, 8 of 10 lymph nodes from noncancer patients expressed CK19 mRNA. Systematic errors due to RNA degradation or incomplete cDNA could be ruled out. It is concluded that HPV16 E6 mRNA is more specific and more sensitive for the detection of tumour cells in SLN than CK19 mRNA. The specificity of CK19 is limited because of low level expression in uninvolved pelvic lymph nodes. ' 2007 Wiley-Liss, Inc.Key words: cervical cancer; disseminated tumour cells; molecular markers; HPV16-E16; cytokeratin 19; quantitative RT-PCR Cervical cancer is the second most common cancer among women world wide, accounting for 493,000 new cases in 2002. 1 The incidence rates vary considerably between different geographic regions, which reflect in part the lack of screening programs in developing countries. Despite the advancement in early diagnosis, improved surgical techniques and adjuvant therapies, approximately 40% of cervical carcinoma patients in countries with a high standard of health care die from the disease. 1 The majority of these deaths is due to metastases. 2 Different parameters such as lymph node metastases, tumour grade, lymph-vascular space involvement (LVSI) and surgical margins are prognostic factors for cervical cancer, with lymph node status as the most important one. 3,4 Patients with histologically uninvolved lymph nodes (pN0) have a better prognosis than women with histologically confirmed lymph node metastasis (pN1) showing 5 year survival rates of 88-93% and 40-63%, respectively. 5-7 Nevertheless 15% of FIGO stage IB patients with pathologically staged negative lymph nodes (pN0) suffer from recurrence. 8 The significance of micrometastases as a predictive factor for recurrent disease is the focus of several recent and ongoing studies. Extensive serial sectioning of lymph nodes that were judged to be free of disease by routine diagnos...

show abstract

“…Telomerase detection on HEC may be more specific compared to other described techniques involving epithelial specific genes (Bostick et al, 1998;Ghossein et al, 1998;Jung et al, 1999) because it allows a direct detection of a marker of epithelial tumour cells. However, further studies should be performed to demonstrate the value of this non-invasive method in determining diagnostic, prognostic and response to therapy.…”

Section: Discussionmentioning

confidence: 99%

“…PCR and RT-PCR have been shown to be of great interest for the detection of chromosomal alteration specific of some haematological malignancies or non-epithelial tumours. Methods, which have been developed for the detection of epithelium-derived cancer cells are primarily based on the amplification of tissue or lineage specific genes (Bostick et al, 1998;Ghossein et al, 1998;Jung et al, 1999). Therefore, due in part to the occurrence of circulating normal epithelial cells, they fail to be specific for the detection of circulating carcinoma cell.…”

mentioning

confidence: 99%

Detection of circulating carcinoma cells by telomerase activity

et al. 2001

View full text Add to dashboard Cite

Summary Telomerase has been shown to be a marker of epithelial cancer cells. We developed a method that allows the detection of circulating carcinoma cells in the blood of cancer patients. Circulating epithelial cells are harvested from peripheral blood mononuclear cells by immunomagnetic separation using BerEP4-coated beads. A telomeric repeat amplification protocol (TRAP)-ELISA is then used to measure telomerase in harvested epithelial cells. This method is specific and sensitive as demonstrated by experiments using BerEP4-positive and negative cell lines. Whereas we never found telomerase activity in harvested epithelial cells (HEC) samples from 30/30 healthy donors, we have detected telomerase activity in HEC from 11/15 (73%) patients with stage IIIB or IV non-small cell lung cancer (NSCLC) patients and from 8/11 (72%) stage C or D (Dukes classification) colon cancer patients. This non-invasive method could be of great value as a diagnostic or prognostic marker, or for monitoring cancer progression.

show abstract

Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients.

Cited by 320 publications

References 34 publications

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer

HPV16‐E6 mRNA is superior to cytokeratin 19 mRNA as a molecular marker for the detection of disseminated tumour cells in sentinel lymph nodes of patients with cervical cancer by quantitative reverse‐transcription PCR

Detection of circulating carcinoma cells by telomerase activity

Contact Info

Product

Resources

About