Sex hormone binding globulin in breast cancer

The present study was undertaken to determine the significance of sex hormone binding globulin, the major and specific binding protein for testosterone and estradiol, in breast cancer. Among breast cancer patients, lower serum levels of Sex hormone binding globulin and higher levels of testosterone were observed. Sex hormone binding globulin showed an inverse relationship with testosterone and total cholesterol, and a direct relation with HDL-cholesterol. By the western blot analyses, Sex hormone binding globulin was detected in all biological samples that we examined. In the breast tumor tissue sections, immuno-staining for Sex hormone binding globulin was confined in cell cytoplasm and 29% cases were positive, which showed no association with the investigated prognostic markers of breast cancer such as ER and HER-2/neu over-expression. In this study, decreased circulating levels of Sex hormone binding globulin in breast cancer patients possibly indicate higher bioavailable estrogens.     

Diagnostic Significance of CA15-3 with Combination of HER-2/neu Values at 85th Percentiles in Breast Cancer

The human epidermal receptor-2/neu (HER-2/neu) oncogene encodes a transmembrane tyrosine kinase receptor. This molecule could have a diagnostic value since the extracellular domain of c-erbB-2 (HER-2) transmembrane is shed into the blood as a circulating antigen. The diagnostic value of serum HER-2/neu was calculated along with the conventional marker carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) at 85th percentiles. Serum levels of breast carcinoma antigens HER-2/neu, CEA and CA15-3 were determined in 175 normal individuals and 268 malignant patients. The soluble form of serum HER-2/neu, CEA and CA15-3 was assayed by enzyme linked immunosorbent assay in control and breast cancer patients prior to treatment. Serum levels of the tested tumor markers HER-2/neu and CA15-3 and CEA were significantly higher in cancer patients compared to controls. At 85th percentile the sensitivity of HER-2/neu was 51.12 %; the specificity was 86.29 % and the overall accuracy was 64.56 %. The sensitivity of CA15-3 was 73.13 %; the specificity was 85.14 % and the overall accuracy was 77.88 %. The sensitivity of the combined testing was 82.84 %; the specificity was 73.71 % and the overall accuracy was 80.01 %. The sensitivity and the overall accuracy of combined testing were higher than those of HER-2/neu and CA15-3 testing single. The combined testing of HER-2/neu and CA15-3 can increase the sensitivity and overall accuracy of breast cancer diagnosis. The results of this study suggest that the use of multiple tumor markers may be employed as combination and at 85th percentiles to assess the prognosis.     

Correlation study of Carcino Embryonic Antigen &; Cancer Antigen 15.3 in pretreated female breast cancer patients

Carcino Embryonic Antigen (CEA) and Cancer Antigen 15.3 (CA15.3) are the most common tumor markers in breast cancer patients. Measurement of circulating tumor markers is a non-invasive quantitative method. Serum levels of CEA and CA 15.3 were studied in female breast cancer patients prior to treatment. To evaluate the utility of these markers, 207 Breast carcinoma patients belonging to all the stages were considered. Healthy age matched 75 female individuals formed the control group. The serum levels of CEA and CA 15.3 were analyzed by Enzyme Linked Immunosorbent Assay (ELISA). Results were taken and compared with stages, tumor size, node and grade. The serum CA 15.3 levels were significant in all the study parameters whereas serum CEA levels showed no significant changes with any of the parameters. Measurement of serum CA 15.3 levels showed significant correlation (24.8%) with advanced stages and larger tumor sizes, whereas serum CEA levels did not show any significant correlation in breast cancer patients prior to treatment.     

Role of Oncofetal Protein CR-1 as a Potential Tumor Marker for Oral Squamous Cell Carcinoma

Cripto-1 (CR-1) is an oncofetal protein with its role as a key factor in early process of carcinoma has been evaluated in cases of various cancers. However, very few studies have reported its role in oral cancer, which is the sixth most common cancer around the world, particularly with high prevalence in developing countries. Oral squamous cell carcinoma (OSCC) is the most predominant (90%) of all the histological types of oral cancer. Late detection, associated with increased morbidity and mortality, is mainly attributed to non-availability of a suitable biomarker for the disease. In the present pilot study, we have evaluated the role of soluble CR-1, in serum as a potential tumor marker for OSCC. CR-1 was estimated using sandwich ELISA in serum samples of 50 biopsy proven OSCC patients (pre and post treatment) along with age and gender matched healthy controls. Immunohistochemistry was also done in corresponding tumor tissue sections to check the expression of CR-1. Pre-treatment CR-1 was found to be 2.25-fold higher in serum of OSCC patients as compared to control (p < 0.0001***), which was reduced to 1.6 folds post treatment (p = 0.0006***). CR-1 levels were comparatively higher in early stage of disease. Upon IHC 80% of the cases were found to be positive for CR-1. This study provides evidence that serum levels of CR-1 are elevated in patients of Oral Squamous Cell Carcinoma, which decrease post treatment. Also, the association of expression of protein with tumor progression predicts CR-1 as a molecule that can be further evaluated as a potential tumor maker in OSCC.     

Clinical usefulness of alterations in sialic acid,sialyl transferase and sialoproteins in breast cancer

Sialic acid, the end moieties of the carbohydrate chains are biologically important and essential for functions of glycoconjugates and are reported to be altered in cancer patients. Two hundred and twenty five breast cancer (BC) patients, 100 patients with benign breast disease (BBD) and 100 healthy females (controls) were enrolled for the study. Eight hundred and twenty four follow-up samples of 225 breast carcinoma patients were also evaluated. The association of sialic acid forms, sialyltransferase and α-2–6 sialoproteins levels with presence and extent as well as prognosis of breast carcinoma was studied. Serum sialic acid forms and sialyltransferase revealed significantly elevated levels among untreated breast cancer patients as compared to the controls, patients with BBD as well as cancer patients in remission. Non-responders showed comparable levels of the markers with those found in breast cancer patients at the time of diagnosis. Higher levels of sialic acid forms at diagnosis were associated with poor prognosis. A positive correlation between serum levels of different forms of sialic acids and extent of malignant disease was observed. The changes in serum proteins with terminal α-2–6 sialic acid correlated well with alterations in the levels of sialic acid forms and sialyltransferase. Malignant tissues showed elevated levels of sialic acid and sialyltransferase as compared to surrounding normal tissues. The results suggested potential utility of these markers in evaluation of clinical outcome.     

Status of epidermal growth factor receptors family in hormone-dependent carcinomas of the breast and prostate with reference to serum lipids and lipoproteins

There are numerous growing evidences of resemblance between carcinomas of the breast and prostate. A total of 45 cases of these two hormone-dependent cancers along with appropriate controls were subjected for status of epidermal growth factor receptors as well as serum lipid profile. Paraffin embedded tissue sections from aforesald tumours were analysed by immunohistochemical staining for epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, estrogen receptor (ER) and progesterone receptor (PgR). Sera from same individuals were studied for serum lipid profile analysis. The study revealed that immunoexpression of all receptor proteins (EGF-R). c-erbB-2 was significantly higher in breast carcinoma. In addition, mean levels of triglycerides, total cholesterol, LDL-cholesterol were found to be significantly elevated while the level of HDL-cholesterol was observed to be lower among patients with breast cancer as compared to matched controls. Further, ER-positive breast cancer cases have significantly higher mean level of HDL-cholesterol when compared with ER-negative breast cancer patients. Contrary to this, no alteration in different serum lipid fractions was noticed among the patients with prostate cancer. However, a positive relationship was noticed between immunoexpressions of EGF-R and c-erbB-2 in prostate cancer.     

Serum oestradiol in women with carcinomas of the breast and uterine cervix

Endogenous oestrogens are thought to be involved in breast cancer, but few studies could show the direct relationship between hormones and pathological process of the disease. In the present study, oestradiol was estimated in the serum of pre-and postmenopausal breast cancer patients along with normal healthy controls and patients with carcinoma of the uterine cervix which is not dependent on oestrogens. Premenopausal patients with breast cancer showed higher levels of oestradiol as compared to premenopausal control women as well as cervical cancer patients. Whereas, no statistically significant differences were observed in serum oestradiol levels amongst postmenopausal groups of breast cancer, cervical cancer and normal women. The result of the study reflects the association of oestradiol as well as its difference in the pathological events of pre and postmenopausal breast cancer.     

Serum gamma glutamyl transpeptidase in breast cancer

Gamma-glutamyl transpeptidase (gamma-GT) levels were estimated in the sera of patients with breast cancer and compared with those of benign breast diseases and healthy controls. Serum gamma-GT levels were found to be significantly increased in patients with breast cancer compared to the controls as well as benign breast diseases. The rise however, was nearly same in all the patients irrespective of histopathology of cancer but was directly related to tumour mass. After mastectomy the levels remained higher upto 3 months. In patients with cancer the rise in serum gamma-GT was significantly higher as compared to those with benign breast diseases. Although gamma-GT is an index of liver diseases, its high level in breast carcinoma suggests the release of the membrane bound constituents from different tissues even in carcinoma.     

Detection of Bone Metastases in Breast Cancer (BC) Patients by Serum Tartrate-Resistant Acid Phosphatase 5b (TRACP 5b), a Bone Resorption Marker and Serum Alkaline Phosphatase (ALP), a Bone Formation Marker,in Lieu of Whole Body Skeletal Scintigraphy with Technetium99m MDP

Bone metastases are a serious problem in patients with advanced cancer disease and their presence usually signifies serious morbidity prior to the patient’s death. In breast cancer patients the incidence of bone metastasis is observed to be very high at 70 %, as seen during post-mortem examination. Bone metastasis is difficult to diagnose, treat or follow clinically without radiological tools. This study was designed to evaluate the utility of a novel bone resorption marker–serum tartrate-resistant acid phosphatase 5b (TRACP5b) and the bone formation marker such as serum total alkaline phosphatase (ALP), in comparison with whole body skeletal scintigraphy with Technetium99m MDP for the diagnosis of bone metastases (BM) in breast cancer (BC) patients. This study is intended to help the clinician to diagnose bone metastasis without resorting to radiological tools, as they are not cost effective and carry the risk of radiation. Experimental design: Four groups of samples were analysed. 1st group consists 52 normal female (cancer free women), 2nd group consists 38 BC patients without bone metastasis, 3rd group consists 27 breast cancer patients with limited bone metastasis (3 or less than 3 skeletal lesions) and 4th group consists 35 breast cancer patients with extensive bone metastasis (4 or more than 4 skeletal lesions), conformed by whole body skeletal scintigraphy with Technetium99m MDP. One way ANOVA was used to compare serum TRACP5b and serum ALP among these groups. Both serum TRACP5b and serum ALP are not markedly elevated in limited bone metastasis but are strongly elevated in extensive bone metastasis (p < 0.0001). As seen in this study the biochemical bone resorption marker, serum TRACP5b, abnormally increased in extensive bone metastasis of breast cancer patients and can be used as a specific marker for bone metastasis in lieu of radiological tools.     

聚合酶链反应检测乙型肝炎患者血清HBVDNA与ELISA检测HBeAg、抗HBe比较研究

应用聚合酶链反应（ＰＣＲ）检测了１５３例各型乙型肝炎患者的血清ＨＢＶＤＮＡ，并与ＥＬＩＳＡ法检测的血清ＨＢｅＡｇ和抗ＨＢｅ结果比较．结果ＨＢｅＡｇ阳性８９例，ＰＣＲ法ＨＢＶＤＮＡ检出率为９２．１３％；抗ＨＢｅ阳性２７例，ＰＣＲ法ＨＢＶＤＮＡ检出率为５１．８５％；ｅ系统用性３７例，ＰＣＲ法ＨＢＶＤＮＡ检出率为４０．５４％．提示抗ＨＢｅ血清学转换不能作为乙型肝炎病毒复制与非复制、病变活动与静止的唯一指标，而应该用或同时用ＨＢＶＤＮＡ作为指标才可靠．     

Circulating peptide and steroid hormone levels in patients with breast cancer

Circulating levels of gonadotropins (FSH,LH), prolactin (PRL), estradiol and progesterone were measured by radioimmunoassay in the sera of 60 patients with histopathologically proven breast cancer. 30 patients belonged to the post and 30 to the premenopausal group. 30 healthy women, 15 each in the pre and post menopausal groups served as controls for the study. Prolactin was elevated in 33% and 26% of pre and post menopausal breast cancer patients respectively. Lower levels of estradiol and progesterone were observed during the luteal phase of the menstrual cycle in premenopausal breast cancer patients. Among postmenopausal patients with breast cancer, LH was elevated in 32%, FSH in 15% and estradiol in 30% of the patients studied.     

Serum lipids, lipoproteins and sex-hormone binding globulin in breast cancer

Serum levels of various lipid parameters, i.e., triglycerides, total cholesterol, alpha lipoprotein or high density lipoprotein (HDL)-cholesterol and beta lipoprotein or low density lipoprotein (LDL)-cholesterol were measured in a total of 138 histologically proven cases of breast cancer along with 146 control women. The mean levels of serum triglycerides, total cholesterol and LDL-cholesterol were found to be significantly higher in breast cancer cases as compared to controls. However, lower mean levels of serum HDL-cholesterol and sex-hormone binding glubulin (SHBG) were observed in breast cancer patients than the control subjects. The results indicate a probable relation between serum lipids and the activity of sex-hormones. Moreover, the study reflects an overall disturbance of lipid metabolism in the pathological process of breast cancer.     

Serum anti — TPO levels in benign and malignant breast tumors

Breast cancer is a hormone dependent neoplasm. Conflicting results regarding the clinical correlation between breast cancer and thyroid diseases have been reported. The objective of this study was to determine the association of anti — TPO levels in patients having complaints of a lump in breast. Serum samples and Fine needle aspiration cytology (FNAC) samples were collected from 31 female patients with a lump in breast between the age group of 20–75 years. 31 age matched normal healthy controls were also examined for the same parameters. Serum samples were analyzed for its anti — TPO levels. FNAC reports confirmed patients as having duct cell carcinoma. They had raised serum anti — TPO levels compared to controls. FNAC results of others (n=26) were reported as fibroadenoma whose anti — TPO levels were less than the controls.     

Serum Levels of Glycoproteins are Elevated in Patients with Ovarian Cancer

Identification of reliable biomarkers for detection and staging of cancer and monitoring the outcome of anticancer therapy has been considered to be of high importance. We aimed to estimate the levels of serum glycoproteins, protein bound-hexose, protein bound hexosamine, protein bound fucose, protein bound sialic acid and protein bound carbohydrate in 32 ovarian cancer patients and compared them with the levels that found in 25 normal subjects. As compared to the normal subjects, all the four fractions of glycoproteins level were significantly elevated in ovarian cancer patients (p < 0.05). Chemotherapy in these patients significantly decreased the levels of serum glycoproteins (p < 0.05). Thus, high levels of serum glycoproteins in ovarian cancer patients could be due to abnormal protein glycosylation indicating malignant transformation of the cells.     

Oxidative Stress and Its Relationship With Adenosine Deaminase Activity in Various Stages of Breast Cancer

Reactive oxygen species (ROS) cause damage to the DNA producing mutations and formation of tumours such as carcinoma of breast. Tumour cells are known to produce ROS at a greater pace than the non-transformed cells. The increased production of reactive oxygen species causes oxidative stress leading to cell proliferation and hence increased inflammatory conditions. The present study was aimed to investigate the role of oxidative stress in the pathogenesis of breast cancer. Females suffering from breast cancer had significantly decreased Superoxide dismutase (SOD) and reduced glutathione (GSH) levels in comparison to normal females. The compromised antioxidant defence system produces the oxidative stress which in turn creates the inflammatory response shown by concomitant increased adenosine deaminase (ADA) activity in female patients. ADA diminishes the protective molecule adenosine. There were significant variations (p < 0.01) in ADA activity with different clinical stages (stage 1–4) of breast cancer suggesting thereby that estimation of ADA activity can be used as a diagnostic tool to detect the stage of cancer along with cytological studies. Mastectomy was performed and post-operatively serum SOD and ADA activity and plasma GSH levels were estimated. There was a statistically significant increase in activity of SOD and levels of GSH while serum ADA activity decreased significantly, suggesting thereby that oxidative stress is responsible for increased cell proliferation and hence the inflammatory conditions in CA breast that got ameliorated post-operatively.     

Study on Urinary Candidate Metabolome for the Early Detection of Breast Cancer

A metabolomic study for determination of certain urinary metabolomes, 1-methyladenosine (1-MA), 1-methylguanosine (1-MG), and 8-hydroxy-2′ deoxyguanosine (8-OHdG) in urine specimens of breast cancer patients. The accuracy of these metabolites and their combined score with cancer antigen 15-3 (CA15-3) was developed to improve the early detection of breast cancer. This study recruited 52 healthy individuals, 47 benign breast tumors, and 167 malignant breast tumor patients. Urine samples were handled to adjust the creatinine concentrations to 8 mg/dL (0.7 mmol/L) and analyzed using GC–MS to detect and quantify the selected urinary metabolomes in urine samples of all participants. The accuracy of individual urinary metabolomes and their combination with CA15-3 were evaluated using multivariate statistical analysis. The cutoff value of CA15-3 was 32.5 U/mL. Cutoff values of 1-MA, 1-MG, and 8-OHdG were 2.19, 2.1, and 7.3 µmol/mmol creatinine, respectively. The concentrations of 1-MA, 1-MG, and 8-OHdG were significantly higher in breast cancer patients, especially in the early-stage. The combination of three urinary metabolomes with CA15-3 improves the diagnostic sensitivity of breast cancer. For the combined score, the area under the curve (AUC) value of combined score ranged from 0.820 to 0.950, with high accuracy, ranged from 77.0 to 95.5%. The most significant AUC (0.973), sensitivity (90.1%), selectivity (94.0%) was recorded at comparing the healthy control with the early-stage of malignant breast cancer. In conclusion, the combination of three urinary metabolomes with serum CA15-3 improves the diagnostic sensitivity of breast cancer.     

Study of Hormone Receptors and Epidermal Growth Factor Expression in Invasive Breast Cancers in a Cohort of Western India

The objective of study was to evaluate and correlate the pathological characteristics of breast cancer patients with estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2/neu) detected by immunohistochemistry and/or fluorescent in situ hybridization method. We have conducted 2 year study of 204 cases of breast cancer at HCG-Medisurge Hospitals, Ahmedabad from 2009 to 2011. Significant correlation was found in ER and PR expression whereas no correlation was found in hormonal receptors and Her2/neu expression. ER and PR positivity increased with advancing age in breast carcinoma patients while not affecting Her2/neu expression. The expression of hormone receptors were higher in infiltrating lobular carcinoma and infiltrating duct carcinoma subtypes of breast carcinoma as compared to other subtypes such medullary and in situ carcinoma. High-grade carcinoma patients were predominantly ER/PR negative and Her2/neu positive as compared to lower grade breast carcinoma whereas high-stage carcinoma patients were ER/PR positive and Her2/neu positive as compared to lower stage breast carcinoma.     

Involvement of Depressive Catecholamines as Thrombosis Risk/Inflammatory Markers in Non-Smoker,Non-Obese Congestive Heart Failure,Linked to Increased Epidermal Growth Factor-Receptor (EGF-R) Production

The EGF-R, also known as HER-1 or erbB-1 (EGF-R/HER-1/erbB-1), is a member of the human epithelial receptor tyrosine kinase family. sEGF-R is considered to play a role in cardiac (patho)physiology. We aimed to investigate whether soluble EGF-R is increased in congestive heart failure (CHF) patients and if related to disease severity. Soluble EGF-R, vitamin D, parathyroid hormone (PTH) was studied, and being evaluated in relation to Ca²⁺, lipids, hsCRP, fibrinogen, serotonin, norepinepherine (NE). The study compared non-smoker, non-obese male CHF patients (n = 50) with age and gender-matched essential hypertension (HTN) patients (n = 20). Moreover, comparison with healthy control volunteers (n = 20) were employed. EGF-R/HER-1/erbB-1 was higher (P = 0.013) in 50 CHF male patients mean 12 ± 0.7 fmol/ml, than in 20 HTN, 9.25 ± 0.6 fmol/ml or in 20 controls, 6.25 ± 1 fmol/ml. Serum EGF-R levels correlated positively with hsCRP and NE, and were highest among CVD patients (n = 70) as well as negatively with vitamin D and HDL-C. EGF-R/HER-1/erbB-1 levels are increased in HTN and more in CHF patients. This study confirms a strong association between catecholamines as well as EGF-R/HER-1/erbB-1 levels with PTH and low vitamin D levels, being related to hyperlipidemia and inflammation (hsCRP and fibrinogen) in CVD. Moreover, contributing to the complex process of the inflammatory component of atherosclerosis in hypertensive patients that leads eventually to CHF.     

Correlation of Levels of IL-6 with Tumor Burden and Receptor Status in Patients of Locally Advanced Carcinoma Breast

Inflammatory pathways have garnered considerable interest in the recent past as an important mediator of the molecular mechanisms leading to carcinogenesis. The present study was conducted to evaluate the correlation of levels of IL-6 with tumor burden and receptor status in patients of locally advanced carcinoma breast. This prospective study was conducted by the collaborative efforts of the departments of Surgery and Biochemistry, Maulana Azad Medical College and associated Lok Nayak Hospital and GB Pant Hospitals, New Delhi. The study population comprised of 30 cases of locally advanced breast carcinoma recruited from the surgical outpatient department. The various parameters that were evaluated include detailed clinico-pathological profile and IL-6 levels. Tissue specimens received after surgeries were examined for the various characteristics indicative of tumor prognosis. Majority of the patients was in the age group of 41–50 years and was postmenopausal. The serum level of IL-6 increased as the disease progressed from T3N1M0 to T4dN2M0 (41.4 ± 31.9 vs. 164.0 ± 31.1 pg/ml respectively). There was significant correlation of IL-6 levels with lymph node involvement, tumor grade, mitotic index and adipose tissue invasion. Emerging molecular markers are being investigated for breast cancer prognosis assessment and prediction of response to chemotherapy including selection of best possible treatment modality. Our study showed that there is progressive increase in IL-6 levels as the stage of disease progresses.