Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer

Abstract

In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-a, IL-1b) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells.

Mammaglobin and maspin transcripts in blood may reflect disease progression and the effect of therapy in breast cancer

“…Therefore, any marker to be used to evaluate the therapeutic effect should be highly specific for tumor cells. Mammaglobin and maspin are two putative breast tissuespecific markers frequently used for detection of occult tumor cells in peripheral blood, bone marrow and lymph nodes of breast cancer patients (Ballestrero et al, 2005). There are no studies in the literature investigating their utility in evaluating response to therapy.…”

“…Breast carcinoma is the most frequent cancer among women, and early detection is one of the most crucial factors for a favorable outcome (Ballestrero et al, 2005). Currently, few diagnostic tools are available to identify the patients at risk, and there is a need for relevant independent prognostic and predictive factors with proven clinical utility to assess an individual patient's risk of disease recurrence (Stojadinovic et al, 2007;Gonzalez-Mancha et al, 2008).…”

Review: Biological relevance of disseminated tumor cells in cancer patients

“…The main drawback of using surrogate tissue-specific markers are false-positive results due to illegitimate low-level of epithelial-or tissue-related transcription in normal cells. [51][52][53] Moreover, heterogeneity in the expression levels of a particular target transcript cannot be predicted. To avoid falsenegative findings due to downregulation of the expression of a single gene, current RT-PCR analyses are therefore frequently performed as multimarker assays.…”

Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review)

“…This expression is limited to the adult mammary gland (120) and related to mammary gland proliferation and differentiation (110,(121)(122)(123)(124)(125), but is commonly absent in healthy breast tissue samples. The detection frequencies seem to vary (126)(127)(128), sensitivity of qPCR for detection of hMAM mRNA shows a broad range even in metastatic breast cancer (128)(129)(130), imposing doubt on the utility of this marker (118), but a combination of hMAM with survivin and hTERT increases the sensitivity of CTC detection (131), pointing towards the use of multimarker PCR (132). Furthermore, no correlation could be found between the expression of hMAM and nodal state, tumour size and grading (109,121,132).…”