Circulating thyroid cancer biomarkers: Current limitations and future prospects.

Differentiated thyroid cancer (DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly to the use of more sensitive diagnostic modalities. Ultrasound-guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, microRNA (miRNA) targets are being investigated as potential biomarkers in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large-scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small-scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation.

Serum resistin is inversely related to breast cancer risk in premenopausal women.

BACKGROUND: Adipokines have been suggested as potential mediators linking obesity and breast cancer. Resistin is the least-studied adipokine with diverse findings regarding its association with disease development and progression. The present study aimed to determine resistin serum levels in breast cancer in relation to the histological type of disease and to investigate their association with breast cancer risk. METHODS: The study included 216 women, of which 163 were diagnosed with breast cancer (58 with IDC, 52 with DCIS and 53 with LN) and 53 were healthy. Serum levels of resistin, leptin and adiponectin were quantitatively determined in duplicates by ELISA. Differences in resistin levels among patient groups were evaluated with Kruskal-Wallis and Mann-Whitney tests. The association of resistin with breast cancer risk was evaluated by multiple logistic regression analysis. RESULTS: Resistin levels varied between histological types of breast cancer (p = 0.044). Significant differences in serum resistin were observed in IDC patients compared to those with DCIS and to controls (p < 0.014 and p < 0.03, respectively). Decreased levels of resistin, adiponectin and leptin were observed in premenopausal patients. Resistin was associated with a reduced risk for ductal carcinoma only in premenopausal women (OR: 0.364, 95% CI: 0.154-0.862, p < 0.022). CONCLUSION: Our findings indicate that resistin levels were inversely related to breast cancer risk in premenopausal women, supporting a protective role of resistin for these patients. Further advances in adipokine research may lead to tangible benefits for overweight/obese women at an increased risk for breast cancer.

Bioanalytical LC-MS Method for the Quantification of Plasma Androgens and Androgen Glucuronides in Breast Cancer.

The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS). A simple and efficient fit-for-purpose method for the simultaneous identification and quantification of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), androsterone glucuronide (ADTG) and androstane-3α, 17ß-diol-17-glucuronide (3α-diol-17G) in human plasma was developed and validated. The presented method permits omission of derivatization, requires a single solid-phase extraction procedure and the chromatographic separation can be achieved on a single C18 analytical column, for all four analytes. The validated method was successfully applied for the analysis of 191 human plasma samples from postmenopausal women with benign breast disease (BBD), lobular neoplasia (LN), ductal carcinoma in situ and invasive ductal carcinoma (IDC). DHEAS plasma levels exhibited significant differences between LN, IDC and BBD patients (P < 0.05). Additionally, ADTG levels were significantly higher in patients with LN compared with those with BBD (P < 0.05).

Prognostic role of sex steroid receptors in pancreatic adenocarcinoma.

From the available literature, it is unclear what proportion of pancreatic adenocarcinomas express estrogen receptors (ERα, ERß), progesterone receptors (PR), and androgen receptors (AR), and if any of these markers have prognostic significance. We aimed to assess (1) the expression and (2) the correlation of the aforementioned markers with clinicopathological parameters and prognosis in patients with pancreatic adenocarcinoma. During a five-year period, 60 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institution. Immunohistochemical stains of the studied markers were quantified by Image analysis system. ERα expression was positively associated with PR expression. Moreover, ERß was inversely associated with the presence of metastases, whereas no significant associations implicated AR. As far as the prognostic significance of the studied receptors is concerned, higher ERα expression correlated with poorer survival at the univariate analysis, but the finding dissipated at the multivariate approach. No significant associations with overall survival were noted regarding the other receptors. The role of sex hormone receptors in the survival from pancreatic adenocarcinoma seems rather limited. Further prospective studies assessing those receptors should ideally be designed in order to confirm our results and possibly outline additional correlations between other steroid receptors and features of pancreatic adenocarcinoma.

Serum irisin levels are lower in patients with breast cancer: association with disease diagnosis and tumor characteristics.

BACKGROUND: Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer. METHODS: Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15-3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated. RESULTS: Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 µg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90%. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 µg/ml, with 62.7% sensitivity and 91.1% specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively). CONCLUSIONS: Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.

Immunohistochemical expression of sex steroid hormone receptors, cell cycle regulators and angiogenesis factors in intraductal papillary mucinous neoplasms: an explorative study.

AIM: The objectives of our explorative study were to (i) evaluate the immunohistochemical expression of sex steroid hormone receptors (estrogen receptor a [ERα], estrogen receptor ß [ERß], progesterone receptor [PR] and androgen receptor [AR]), angiogenesis factors (vascular endothelial growth factor [VEGF] and inhibitor of differentiation/DNA synthesis 1 [Id-1]) and cell-cycle regulators (cyclin D1, p16 and p27) in intraductal papillary mucinous neoplasms (IPMNs) in comparison to normal adjacent pancreatic tissues and (ii) assess their correlation with the grade and histological sub-type of those lesions. MATERIALS AND METHODS: Paraffin-embedded specimens from 12 consecutive patients with IPMNs were immunostained for the studied markers and staining quantification was assessed by an image analysis system. RESULTS: AR H-score and cyclin D1 H-score were significantly higher in the IPMN lesions (0.86±0.33 vs. 0.57±0.12 in the normal tissue, p=0.010 and 0.47±0.23 vs. 0.21±0.20 in the normal tissue, p=0.019, respectively). No significant differences were noted regarding the expression of ERα, ERß, PR, p16, p27, VEGF, Id-1 or MVD. Moreover, no significant associations were found between the expression of studied markers and grade or histological subtype. CONCLUSION: Our study showed higher expression of AR and cyclin D1 in IPMNs compared to normal pancreatic ducts without any association between AR and cyclin D1 expression and IPMNs' grade or subtype.

Interleukins as markers of inflammation in malignant and benign thyroid disease.

BACKGROUND: Thyroid disorders, including thyroid cancer and autoimmune thyroid diseases, have been closely associated with inflammation. OBJECTIVE: This study aims to investigate the role of inflammation in thyroid disease by assessing serum cytokine levels in patients with malignant and benign thyroid conditions. METHODS: Serum levels of ten interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 and IL-13) were quantitatively determined in 20 patients with thyroid cancer, 38 patients with benign thyroid disease and 50 healthy controls by multiplex technology. RESULTS: Serum IL-1ß, IL-2, IL-4, IL-5 and IL-6 levels were strongly associated with each other. IL-10 and IL-12 correlated with IL-1ß, IL-5, IL-6, and with each other. Age was inversely correlated with serum levels of IL-2, IL-4 and IL-13. A positive correlation between T3 and IL-13 levels was also observed. Significantly higher levels of IL-6, IL-7, IL-10 and IL-13, as well as significantly lower levels of IL-8 were observed in patients with benign and malignant thyroid disease compared to controls. The combination of IL-13 and IL-8 in a two-marker panel was highly efficient in discriminating thyroid disorders (AUC 0.90). CONCLUSIONS: Malignant and benign thyroid conditions are associated with altered expression levels of interleukins, supporting the association between thyroid disease and underlying inflammatory processes.

Tumor suppressor PTEN in breast cancer: heterozygosity, mutations and protein expression.

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated human tumor suppressor genes, implicated in cell growth and survival and suppressing tumor formation. Loss of PTEN activity, either at the protein or genomic level, has been related to many primary and metastatic malignancies including breast cancer. The present study investigates the heterozygosity, mutation spectrum and protein expression of PTEN in 43 patients with breast cancer or precursor lesions of the breast and 10 healthy individuals. Microsatellite analysis at the PTEN locus using D10S215, D10S541 and D10S579 markers indicated that the observed heterozygosity (Ho) is lower than the expected heterozygosity (Hs) in benign and malignant breast disease. Mutational analysis in exons 1, 5, 7 and 9 of the PTEN gene revealed several mutations, most of which cause truncation of the PTEN protein and consequently loss of activity. Increased circulating levels of PTEN and phosphorylated PTEN protein were also observed by immunostaining in patients with breast cancer and precursor breast lesions. In support, increased PTEN protein expression was detected in corresponding tissue specimens. Our data suggest an association between breast cancer and PTEN mutations, resulting in the production of truncated forms of the corresponding protein, thus indicating that breast carcinogenesis is potentially related to PTEN loss of activity rather than loss of expression. Peripheral blood sampling may provide an advantageous application for the determination of PTEN gene mutations and its protein expression in human cancer.

Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry: could it raise new perspectives in the diagnostic field of hormone-dependent malignancies?

Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC-MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC-MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.

The current status of positron emission mammography in breast cancer diagnosis.

Mammography is currently the standard breast cancer screening procedure, even though it is constrained by low specificity in the detection of malignancy and low sensitivity in women with dense breast tissue. Modern imaging modalities, such as magnetic resonance imaging (MRI), have been developed in an effort to replace or complement mammography, because the early detection of breast cancer is critical for efficient treatment and long-term survival of patients. Nuclear medicine imaging technology has been introduced in the field of oncology with the development of positron emission tomography (PET), positron emission tomography/computed tomography (PET/CT) and, ultimately, positron emission mammography (PEM). PET offers the advantage of precise diagnosis, by measuring metabolism with the use of a radiotracer and identifying changes at the cellular level. PET/CT imaging allows for a more accurate assessment by merging the anatomic localization to the functional image. However, both techniques have not yet been established as diagnostic tools in early breast cancer detection, primarily because of low sensitivity, especially for sub-centimeter and low-grade tumors. PEM, a breast-specific device with increased spatial resolution, has been developed in order to overcome these limitations. It has demonstrated higher detectability than PET/CT and comparable or better sensitivity than MRI. The ability to target the lesions visible in PEM with PEM-guided breast biopsy systems adds to its usability in the early diagnosis of breast cancer. The results from recent studies summarized in this review indicate that PEM may prove to be a useful first-line diagnostic tool, although further evaluation and improvement are required.

Effect of breast cancer adjuvant therapies on potential biomarkers of pulmonary inflammation.

BACKGROUND: The aim of this study was to investigate the effect of breast cancer adjuvant therapies on the levels of circulating surfactant protein-D (SP-D), C-Reactive protein (CRP) and soluble receptor for advanced glycation end-products (sRAGE), as potential biomarkers of subclinical pulmonary inflammation. MATERIALS AND METHODS: The soluble molecules were serially determined in 38 patients, prior to the initiation of radiation therapy (RT) and during adjuvant treatment, using immunoassays. RESULTS: Significantly higher levels of all three biomarkers were observed in patients prior to the initiation of RT compared to healthy controls (CRP: p<0.001, SP-D: p<0.05, sRAGE: p<0.05). SP-D levels exhibited a gradual increase after RT and during follow-up (p<0.005). Patients treated with a combination of RT and hormonal therapy presented a significant, but less pronounced, increase in SP-D and a significant decrease in CRP compared to those who did not receive hormonal therapy (p=0.0428 and p=0.0116, respectively). Patients treated with a combination of RT and trastuzumab presented a significant increase in SP-D levels (p=0.0310). CONCLUSION: The average rate of change in the levels of circulating SP-D and CRP during postoperative irradiation and adjuvant hormonal therapy suggests that the combined therapeutic regiment may potentially exert important anti-inflammatory effects on the lung. On the contrary, combined administration of RT and trastuzumab is likely to induce or provoke pulmonary inflammation.

Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in breast cancer early diagnosis.

Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.

Soluble human leukocyte antigen-G expression in patients with ductal and lobular breast malignancy.

BACKGROUND: Human leukocyte antigen-G (HLA-G) has been closely associated with diagnosis and prognosis in many types of human cancer. The current study aims to investigate soluble (s) HLA-G expression in patients with breast malignancy. PATIENTS AND METHODS: sHLA-G plasma expression was determined in 120 patients with breast cancer and 40 healthy controls using enzyme-linked immunosorbent assay. RESULTS: Plasma sHLA-G levels were significantly higher in breast cancer patients compared to healthy controls (p<0.001), with an area under the receiver operating characteristic (ROC) curve of 0.735 (95% Confidence interval=0.630-0.841, p<0.001). Significantly increased sHLA-G expression was detected in patients with mixed type of coexisting ductal and lobular breast lesions, compared to patients with pure ductal carcinoma or pure lobular neoplasia (p<0.05). CONCLUSION: sHLA-G expression is closely associated with the histological type of breast cancer. Our findings support the application of sHLA-G as a potential biomarker in body fluids for preoperative breast cancer detection and diagnosis.

Serum levels of HSP90 in the continuum of breast ductal and lobular lesions.

BACKGROUND: Heat-shock protein 90 (HSP90) is an abundant protein in mammalian cells. It interacts with a variety of proteins that play key roles in breast neoplasia. This is the first study to assess serum levels of HSP90 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and infiltrative lobular carcinoma (ILC). PATIENTS AND METHODS: Serum concentrations of HSP90 in women with benign (n=34), ADH (n=26), DCIS (n=30), IDC (n=29), LN (n=20) and ILC (n=9) lesions were determined with immunoenzymatic assays. For the evaluation of serum concentrations along the transition from benign through precursor and preinvasive to invasive lesion, the severity of diagnosis was treated as an ordinal variable. RESULTS: No significant association was demonstrated between serum HSP90 levels and the severity of the lesion in ductal and lobular series. The post hoc comparison between the lobular and ductal precursor lesions (i.e. ADH vs. LN) did not yield a statistically significant difference. Similarly, the post hoc comparison between the lobular and ductal invasive carcinomas (i.e. IDC vs. ILC) did not point to a statistically significant difference. CONCLUSION: This is the first study evaluating HSP90 serum levels in both lobular and ductal lesions of the breast. Contrary to published pathological findings according to which HSP90 exhibits significant variability along both series, such a finding was not replicated for the level of serum HSP90 concentrations.

Vacuum-assisted breast biopsy: more cores, more hematomas?

BACKGROUND: Vacuum-assisted breast biopsy (VABB) is used for the diagnosis of non-palpable breast lesions. Hematoma has been recognized as the main complication of the procedure. Its main disadvantage is the underestimation rate. Generally speaking, approximately up to 24 cores are excised in most published series. It has been suggested that excision of more cores per lesion can reduce the underestimation rate. The present study aims to evaluate hematoma formation with regard to the number of cores excised. PATIENTS AND METHODS: A total of 660 women underwent VABB; 232 women were allocated to the standard protocol (24-36 cores excised, 2-3 offsets) and 428 women were allocated to the extended protocol (96 cores excised, 8 offsets). Cases were derived from a double blind study, as well as from the periods before (standard protocol) and after (mainly extended protocol) the study. In all cases, the occurrence of organized hematomas within the subsequent 20 days was followed up by ultrasound. RESULTS: In the standard protocol, the frequency of clinically significant and subsequently organized hematomas was 3.5%. However, in the extended protocol the respective hematoma percentage was 7.5%. Clinically significant and subsequently organized hematomas were significantly more frequent in the extended protocol (Pearson's chi-squared=4.29, p=0.038). CONCLUSION: Despite the superiority of the extended protocol in terms of underestimation, the approximately two-fold increase in hematoma occurrence prompts the need for careful patient selection prior to its performance.

Electrochemotherapy in cancer patients: first clinical trial in Greece.

Electrochemotherapy is currently undergoing intensive investigation in the field of local control of cancer. In Greece, five medical centers have co-operated to perform ECT for the efficient management of growing, recurrent or newly emerging cutaneous and subcutaneous tumor nodules. ECT was applied alone or in combination with external beam radiation therapy, brachytherapy and surgery in 52 cancer patients, using bleomycin according to standard protocols. The treatment response for various tumors was 63.83% complete, 31.91% partial, and 95.74% overall of the treated nodules. Patients exerted neither systemic nor local side-effects. The results of ECT performance in Greece provided evidence that this new treatment strategy is safe and permits the effective control of tumors of various origins and histological types.

Serum MMPs and TIMPs: may be predictors of breast carcinogenesis?

BACKGROUND: The involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions. METHODS: On women with benign (n=65), precursor [ADH (n=18) and LN (n=15)], preinvasive [DCIS (n=32)] and invasive [IDC (n=28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10mm in diameter, as estimated on the mammographic views. Statistical analysis followed. RESULTS: TIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup. CONCLUSION: TIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.

Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease.

BACKGROUND: Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. METHODS: The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. RESULTS: Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients. CONCLUSION: These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

Excisional breast biopsy under local anesthesia: stress-related neuroendocrine, metabolic and immune reactions during the procedure.

AIM: The aim of this study was to evaluate three axes: the sympathetic system (adrenaline and noradrenaline), surgical stress-related endocrine factors (prolactin, cortisol, insulin, glucose and growth hormone) and inflammatory cytokines (IL-1alpha, IL-1beta and IL-6) during excisional breast biopsy under local anesthesia (EBBLA). PATIENTS AND METHODS: On 14 women undergoing EBBLA, all the aforementioned molecules were measured in peripheral venous blood samples prior (baseline), during (at 10 and 30 minutes), at the end of EBBLA (46+/-9 minutes) and one hour after its end. RESULTS: Serum growth hormone glucose and cortisol were found elevated at the 10th and 30th minute and at the end of EBBLA. Serum prolactin increased only at the 30th minute. Of notice, none of the measured parameters was found elevated one hour after the end of biopsy. Concerning adrenaline, noradrenaline and interleukins, no significant changes were documented. CONCLUSION: During EBBLA, significant stress-related endocrine events arise. However, no significant sympathetic / cytokine triggering was noted.