Breast Neoplasms: Galazios G

Koukourakis MI, Giatromanolaki A, Galazios G, Sivridis E. · Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece. · Br J Cancer. · Pubmed #12618880 links to  free full text

Abstract: Large primary breast tumours and extensive lymph node involvement are linked to a high rate of local recurrence after surgery. In 10-20% of such high-risk breast cancer patients, local relapse will occur despite postoperative radiotherapy. In the present study, we investigated whether molecular features, such as angiogenesis, cancer cell proliferation, steroid receptor expression, c-erbB-2 oncoprotein overexpression, p53 protein nuclear accumulation or bcl-2 antiapoptotic protein expression, can predict failure of local therapy. We further examined as to which subgroups of patients could benefit from altered fractionation schemes of radiotherapy. In univariate analysis, high intratumoural angiogenesis, c-erbB overexpression and mutant-p53 nuclear accumulation were significantly associated with increased relapse rate (P=0.0002, 0.009 and 0.05, respectively). In multivariate analysis, the microvessel density and the c-erbB-2 status were independent and significant factors related to local relapse (P=0.001, t-ratio 3.36 and P=0.02, t-ratio 2.26, respectively). Hypofractionated and accelerated radiotherapy supported with amifostine (HypoARC regimen) was significantly more effective than standard radiotherapy in cases with high cancer cell proliferation index, c-erbB-2 and p53 overexpression. High angiogenesis, however, was linked with local relapse regardless of the radiotherapy regimen.

Limberis V, Romanidis C, Galazios G, Koutsougeras G, Papadopoulos N, Lambropoulou M, Simopoulos C. · Department of Obstetrics & Gynecology, Democritus University of Thrace, Greece. · Eur J Gynaecol Oncol. · Pubmed #19317265 No free full text.

Abstract: BACKGROUND: Frozen section biopsy has been widely used for intraoperative diagnosis and evaluation of sentinel lymph nodes, so a decision can be made regarding whether to perform axillary clearance during primary surgery. This study aims to discuss the reliability of a simpler and faster method - touch imprint cytology - in the interpretation of metastasis from breast cancer. METHODS: A retrospective review of 41 sentinel lymph node biopsies from patients with breast cancer were examined by intraoperative imprint cytology using rapid Diff-Quick staining. Paraffin-embedded permanent sections were examined using hematoxylin and eosin stained sections from the sentinel lymph nodes in collaboration with the employment of an anti-cytokeratin antibody. RESULTS: Sixteen of all sentinel nodes harbored metastases in the paraffin sections, of which all 16 were identified by imprint cytology (sensitivity 93%). CONCLUSION: Touch imprint cytology is a fast and reliable alternative for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.

Papadopoulou E, Anagnostopoulos K, Tripsianis G, Tentes I, Kakolyris S, Galazios G, Sivridis E, Simopoulos K, Kortsaris A. · Laboratory of Biochemistry, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. · Neoplasma. · Pubmed #18348656 No free full text.

Abstract: The present study was conducted to clarify the predictive and prognostic significance of serum TGF-I(2)1 in breast cancer in relation to Ile655Val single nucleotide polymorphism (SNP) of human epidermal growth factor receptor-2 (HER-2). In a case-control study, 56 consecutive patients with primary breast cancer were prospectively included and evaluated. The control group consisted of 45 healthy women. Serum concentrations of TGF-I(2)1 were measured by quantitative sandwich enzyme immunoassay (ELISA). HER-2 SNP was genotyped using PCR-RFLP method. Serum levels of TGF-I(2)1 were significantly increased in breast cancer patients compared to healthy controls (p<0.001). For the evaluation of the diagnostic significance of serum TGF-I(2)1 the area under the receiver operating characteristic (ROC) curve (AUC) was 0.804, while the optimal cut-off point of 30.86 ng/ml was determined to classify breast cancer patients, which yielded sensitivity of 77%, specificity of 78% and accuracy of 77%. Significantly elevated serum TGF-I(2)1 levels were associated with advanced stages (p=0.023), positive lymph nodes (p=0.019) and postmenopausal status (p=0.031). A marginal trend towards higher TGF-I(2)1 levels was found among patients with Val-containing genotypes compared to homozygous Ile-Ile (p=0.094). In multivariate analysis lymph node metastases (p=0.009) remained the only significant independent determinant of high TGF-I(2)1 levels. With regard to prognostic significance for advanced stages (AUC, 0.704) and lymph node metastasis (AUC, 0.683), when the optimal cut-off value was set at 65.15 pg/ml, the sensitivity was 86% and 67%, the specificity was 60% and 62% and accuracy was 66% and 64%, respectively. Survival was shorter in patients with increased serum TGF-I(2)1 (36 months vs 46 months, p=0.022). Multivariate analysis demonstrated a marginal prognostic significance of serum TGF-I(2)1 for survival (p=0.072). The combination of high TGF-I(2)1 and Val-Val genotype predicts a worse prognosis than high serum TGF-I(2)1 alone. Our findings suggest that serum TGF-I(2)1 is involved in tumor malignancy and lymph node metastasis and could be used clinically as a useful tumor marker for evaluation, the extension and the outcome of the disease. They also provide clinical evidence for a significant association between HER-2 Ile655Val SNP and serum TGF-I(2)1, resulting to more aggressive phenotype of the tumor and poor prognosis.

Papadopoulou E, Tripsianis G, Anagnostopoulos K, Tentes I, Kakolyris S, Galazios G, Sivridis E, Simopoulos K, Kortsaris A. · Laboratory of Biochemistry, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. · Neoplasma. · Pubmed #18237248 No free full text.

Abstract: HER-2 (human epidermal growth factor receptor-2) proto-oncogene is a member of the EGFR family and plays an important role in the regulation of cell growth, differentiation and survival and is involved in the regulation of normal breast growth and development. Alterations of HER-2 have been associated with carcinogenesis and poor prognosis of breast cancer. The present case-control study was conducted to clarify the predictive and prognostic significance of serum HER-2 protein in breast cancer patients in relation to Ile655Val single nucleotide polymorphism (SNP) of this gene. Fifty-six consecutive patients with primary breast cancer and 45 healthy women were prospectively included and evaluated. Serum levels of HER-2 were significantly increased in breast cancer patients compared to healthy controls (p=0.035). The optimal cut-off point of 1.98 ng/ml, which was determined to classify breast cancer patients, yielded sensitivity of 54%, specificity of 73% and accuracy of 62%. Significantly elevated serum HER-2 levels were associated with lymphovascular invasion (p=0.022), poor differentiation (p=0.011), advanced clinical stages (p=0.001), lymph node metastasis (p=0.011), higher number of positive lymph nodes (p=0.007) and the immunohistochemical overexpression of HER-2 protein (p=0.016). Regarding to HER-2 Ile655Val SNP, Ile-Val and Val-Val genotypes exhibited highly significant serum HER-2 elevation compared to homozygous Ile-Ile (both p<0.001). In multivariate analysis advanced stages (p=0.003) and Val-containing genotypes (p=0.009) remained the two significant independent determinants of high HER-2 levels. Survival analysis demonstrated an independent prognostic significance of homozygous Val-Val genotype for reduced survival (p=0.045), but not of serum HER-2 (p=0.181). Our findings confirm that serum HER-2 could be used clinically as a useful tumor marker for the diagnosis and the progression of breast cancer. Furthermore, they provide clinical evidence that HER-2 Ile655Val SNP does affect serum HER-2 levels and it can be regarded as a predictive biomarker for breast cancer patients with poor prognosis.

Papadopoulou E, Simopoulos K, Tripsianis G, Tentes I, Anagnostopoulos K, Sivridis E, Galazios G, Kortsaris A. · Laboratory of Biochemistry, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. · Neoplasma. · Pubmed #17918664 No free full text.

Abstract: Alterations of c-erbB-2 (neu or HER-2) proto-oncogene have been associated with carcinogenesis and poor prognosis of breast cancer. A single nucleotide polymorphism (SNP) at codon 655 resulting in a G to A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer. This study aims to determine the prevalence of the HER-2 genotype and its association with breast cancer in the Greek Christian and Greek Muslim population of Thrace, Greece. In this case-control study, we genotyped 56 patients (43 Christians and 13 Muslims) with primary breast cancer and 45 healthy women (32 Christians and 13 Muslims) for the Ile655Val polymorphism, with the PCR-RFLP method. The Val allele and the Val-containing genotypes were significantly more frequent in Muslims than in Christians (p=0.020 and p=0.008, respectively). Among the Greek Christian population, a 5-fold and a 3.1-fold increase in risk of breast cancer was associated with the Val-Val genotype and the Ile-Val or Val-Val genotypes (95% CI, 1.3-18.4; p=0.017 and aOR, 3.1; 95% CI, 1.2-8.3; p=0.025; respectively) compared to homozygous Ile-Ile. No significant association was found in the Muslim population. Among the entire cohort, the Val allele confers a modest increase in breast cancer risk (OR, 2.6; 95% CI, 0.9-7.6; p=0.076, for Val-Val and OR, 2.2; 95% CI, 0.9-5.2; p=0.079 for Ile-Val or Val-Val). This effect was even more pronounced in younger women. Among breast cancer patients, invasive carcinomas, low differentiation tumors, advanced stages, positive lymph nodes, high number of lymph nodes and HER-2 overexpression were more frequent in patients with allele Val than those with allele Ile. Our study proposes the allelic imbalance of Ile655Val polymorphism between Greek Christian and Greek Muslim populations of Thrace contributes to the inconsistent association between this SNP and breast cancer risk across these two different ethnic groups. The association of the HER-2 genotype with clinicopathologic characteristics and HER-2 expression may indicate its possible implication on the more aggressive phenotype.

Sivridis E, Giatromanolaki A, Galazios G, Koukourakis MI. · Department of Pathology, Democritus University of Thrace Medical School, P.O. Box 128, Alexandroupolis 68100, Greece. · Breast. · Pubmed #16135406 No free full text.

Abstract: The number of positive lymph nodes (+LNs) is the only node-related prognostic factor recognized by the American Joint Committee TNM system for breast cancer. In this study, we evaluated additional node-related prognostic factors in node-positive breast carcinomas. One hundred and thirty-four patients with infiltrating ductal carcinomas and axillary +LNs, who had been treated with modified radical mastectomy, were analyzed. Metastatic lymph nodes were evaluated for traditional prognostic factors, i.e., the number of involved nodes and the extranodal extension, but also for a variety of other node-related characteristics, such as nodal tumor burden and maximum size of tumor deposits, necrosis, stromatogenesis, extranodal vascular involvement, and nodal matting. The results reaffirmed the prognostic significance of metastasis in 1-3 vs. 4-7 axillary lymph nodes and, in addition, revealed the importance of 4 +LNs as a cut-off point for breast tumor aggressiveness, given that survival curves for 4-7 vs. >7 +LNs were indifferent. Interestingly, nodal tumor burden, when extensive, was statistically an adverse prognostic factor. Prognosis was equally poor if metastases to regional nodes showed extensive nodal necrosis or extensive nodal stromatogenesis, if there was extranodal spread, extranodal vascular involvement, or if the axillary +LNs were matted. In multivariate analysis, intranodal necrosis and extranodal vascular involvement were the only node-related features with a significant and independent prognostic function. Node-related pathological features in node-positive breast carcinomas are important in determining prognosis. Intranodal necrosis and extranodal tumor emboli should be considered, in parallel with the number of +LNs, in subsequent treatment design.

Galazios G, Dafopoulos K, Gardikis S, Sigalas J, Tamiolakis D, Liberis V, Sivridis E. · Department of Obstetrics and Gynecology, Democritus University of Thrace Medical School, Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #12691328 No free full text.

Abstract: Phyllodes tumor of the breast is an unusual tumor with an incidence of 1 in 100,000. In particular, it is a very rare neoplasm in adolescent girls and young women. The authors present a case of a 13-year-old adolescent girl with a large unilateral palpable mass in her right breast. The diagnosis of cystosarcoma phyllodes was made in a frozen section after wide local excision. The management and the cytological and histological characteristics are described with particular reference to the very unusual clinical presentation in this patient.

Anninos PA, Kotini A, Koutlaki N, Adamopoulos A, Galazios G, Anastasiadis P. · Lab. of Medical Physics, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. · Eur J Gynaecol Oncol. · Pubmed #11214617 No free full text.

Abstract: PURPOSE: Breast cancer mortality rates have not changed during the past 60 years despite significant advances in screening methods. It is tempting therefore to use novel technology in order to better understand breast oncology. In this study we investigated the biomagnetic activity obtained in benign and malignant breast lesions using a single channel biomagnetometer SQUID (Superconducting Quantum Interference Device) in order to assess the method's efficacy in the differential diagnosis of these two types of lesions and its establishment as a screening technique. METHOD: Magnetic recordings were obtained from 21 patients with palpable breast lumps. Of these 11 were invasive carcinomas and 10 were benign breast lesions. We used non-linear analysis to investigate whether there is any biological differentiation in the dynamics in these two types of lesions. RESULTS: High amplitudes characterized the waveform of a malignant breast lesion whereas in benign breast lesions the corresponding amplitudes were low. Using the application of non-linear analysis we observed a clear saturation value for the dimension of malignant breast lesions and no saturation for benign ones. DISCUSSION: Biomagnetic measurements with the SQUID and the application of non-linear analysis are promising procedures in assessing and differentiating breast tumors.

Tamiolakis D, Papadopoulos N, Venizelos J, Lambropoulou M, Romanidis C, Petrakis G, Limberis V, Galazios G, Koutsougeras G, Simopoulos C. · Department of Cytology, Regional Hospital of Chania, Greece. · Onkologie. · Pubmed #16974114 No free full text.

Abstract: BACKGROUND: Imprint cytology may provide a fast and accurate method for intraoperative screening of sentinel lymph nodes, so a decision can be made regarding whether to perform axillary clearance during primary surgery. If the findings are negative, in many cases axillary dissection can be omitted. Patients and METHODS: 128 sentinel nodes from a cohort of 87 patients that had been identified using technetium-99m nanocolloid as a radioactive tracer and Patent blue dye were dissected for rapid Diff-Quick stained touch preparations. Intraoperative evaluation of sentinel node status by imprint cytology was correlated with histopathological results of permanent sections. Tumor-negative nodes in routine paraffin sections were further investigated with the employment of an anti-cytokeratin antibody. RESULTS: 36 of all sentinel nodes harbored metastases in the paraffin sections, of which 32 were identified by imprint cytology (sensitivity 88.8%). 3 sentinel nodes were positive by imprint cytology and negative by histopathology of the paraffin sections. Comparison of the results of the touch preparations with the final histopathology (hematoxylin-eosin and anticytokeratin antibody stains) demonstrated a sensitivity of 83.3% and a negative predictive value of 92.5%. The specificity and positive predictive value were 100% each. CONCLUSIONS: Touch imprint cytology is potentially useful for intraoperative evaluation of sentinel lymph nodes in breast cancer patients.