Comparison of serum NEDD-9, CA 15-3, and CEA levels and PET metabolic parameters in breast cancer patients with 18 F-FDG PET / CT

SUMMARY OBJECTIVE Analyze the over expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) deregulated associated with a poor prognosis in various carcinomas. Our objective was to investigate the relationship between the levels of NEDD-9, CA 15-3, and CEA and PET (SUVmax, MTV40, TLG40) with the clinical parameters of patients with breast cancer (BC). METHODS One hundred and eleven patients (82 BC patients who underwent 18F-FDG PET/CT and 29 healthy controls) were evaluated. SUVmax, MTV, and TLG of the primary tumor were compared with the molecular and histopathological subtypes. 18F-FDG, MTV, and TLG were evaluated based on the clinical data, i.e., nodal involvement, distant metastasis, ER and PR status, Ki-67, serum levels of NEDD-9, CA15-3, and CEA. We compared the NEDD-9 in the BC and healthy control groups. RESULTS The mean ± SD of SUVmax in the 82 patients was 13.0 ± 8.6. A statistically significant relationship (p = 0.022) was found between the molecular subtypes and 18F-FDG uptake. The relationship between 18F-FDG uptake and TLG measured in patients <50 years, ER-PR negativity, and HER2 positivity were statistically significant (p=0.015, 0.007, 0.046, and 0.001, respectively). MTV40, TLG40, and CA 15-3 in metastatic patients were statistically significant (p=0.004, 0.005, and 0.003, respectively). NEDD-9 in the BC group was significantly higher than in the healthy group (p=0.017). There was a positive correlation between SUVmax and Ki67 and CA 15-3; MTV40 and CEA; CA 15-3, CEA, SUVmax, and MTV40; a negative correlation was found between CEA, TLG40, and age. CONCLUSION The use of SUVmax, MTV40, and TLG40 parameters with NEDD-9 and tumor markers has been shown to provide a high diagnostic, predictive, and prognostic value for the management of BC. This is considered to be the basis of interventions focused on the treatment objectives related to NEDD-9.

RESUMO OBJETIVO Analisar a associação da superrexpressão das células NEDD-9 ao prognóstico negativo em vários tipos de carcinoma. Nosso objetivo foi investigar a relação entre os níveis de NEDD-9, CA 15-3 e CEA e PET (SUVmax, MTV40, TLG) e os parâmetros clínicos em pacientes com câncer de mama (CM). MÉTODOS Cento e onze pacientes (82 pacientes de CM submetidos a 18F-FDG PET/TC e 29 controles saudáveis) foram avaliados. SUVmax, MTV, e TLG do tumor primário foram comparados nos subtipos molecular e histopatológico. A captação de 18F-FDG, MTV, e TLG foi avaliada com base em dados clínicos (envolvimento nodal, metástase distante, status de ER e PR, Ki-67, níveis séricos de NEDD-9, CA15-3 e CEA). Foi comparada a NEDD-9 do grupo de CM e o controle saudável. RESULTADOS A média ± DP de SUVmax de 82 pacientes foi de 13,0 ± 8,6. Uma relação estatisticamente significativa (p=0,022) foi encontrada entre subtipos moleculares e captação de 18F-FDG. A relação entre captação de 18F-FDG e TLG medida em pacientes com idade <50 anos, ER-PR negativo e HER2 positivo foi estatisticamente significativa (p=0,015; 0,007; 0,046; e 0,001, respectivamente). MTV40, TLG40 e CA 15-3 em pacientes metastáticos foram estatisticamente significantes (p=0,004, 0,005 e 0,003, respectivamente). NEDD-9 no grupo BC foi significativamente maior do que no grupo saudável (p=0,017). Uma correlação positiva foi encontrada entre SUVmax e Ki67 e CA 15-3; MTV40 e CEA; CA 15-3, CEA, SUVmax e MTV40; uma correlação negativa foi encontrada entre CEA, TLG40 e idade. CONCLUSÃO O uso dos parâmetros SUVmax, MTV40 e TLG40 com NEDD-9 e marcadores tumorais demonstrou um alto valor diagnóstico, preditivo e prognóstico para o manejo do CM. Isso é considerado a base para intervenções focadas nos objetivos de tratamento relacionados às NEDD9.

Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer

BACKGROUND: Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. METHODS: The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). RESULTS: The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). CONCLUSIONS: These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

Serial tumour markers serum carcinoembryonic antigen and cancer antigen 15-3 assays in detecting symptomatic metastasis in breast cancer patients

The value of serum tumour markers in the prognosis of patients with breast cancer is controversial. This prospective study in Yazd, Islamic Republic of Iran, assessed the value of the tumour markers carcinoembryonic antigen [CEA] and cancer antigen [CA] 15-3 in 159 patients with primary breast cancer. CEA and CA15-3 assays [mean 14 per patient] were performed at diagnosis, end of surgery and chemotherapy and every 3 months in the first 2 years and every 6 months in second 2 years of the follow-up period. During follow-up, 33 patients [20.8%] presented symptomatic metastasis. A significant relationship was seen between metastasis status and positive CEA and CA15-3 levels. The sensitivity and specificity were 66.7% and 98.4% for CEA respectively and 84.8% and 91.3% for CA15-3 respectively. Optimum cut-offs were 4.95 ng/mL and 30.5 U/mL for CEA and CA15-3 respectively

MUC5B expression in middle ear effusions: the main gel-forming mucin responsible for viscous properties of middle ear effusions

Several mucin genes are expressed in the middle ear mucosa resulting in the development of middle ear effusion. However, the detailed mucin protein expression in middle ear effusions has not been studied in individual effusions. This study aimed to explore the expression patterns of the 3 main secretory mucins, known to be expressed in the air-ways, in individual middle ear effusions with studying the possible correlation with the effusion viscosity. Middle ear effusions were collected under general anesthesia from 30 children with otitis media with effusion. The viscosity of individual effusions was studied. Mucins were extracted from the individual effusions and their antigenic identity was studied with ELISA. Mucoid effusions have significantly higher viscosity and mucin content than serous effusions. MUCs2, 5AC and 5B were expressed in middle ear effusions within a wide range. MUC5B was the most abundant mucin with significantly strong positive correlation with the viscosity of middle ear effusions. Middle ear epithelium expresses MUC5B as the major secretory mucin which is likely to be the main determinant of the viscosity, and hence physical and biological characteristics, of middle ear effusions. A secondary role is played by MUC5AC and, to a small extent, by MUC2. This could have significant clinical implications. MUCsSB, 5AC and 2 are expressed in middle ear effusions with MUC5B representing the major secretory mucin which is also the main determinant of mucin viscosity. The clinical implications of these findings need further studies

Comparison of bone scintigraphy with serum tumor markers of CA 15-3 and carcinoembryonic antigen in patients with breast carcinoma

To compare the bone scintigraphy findings with a carcinoembryonic antigen [CEA] and cancer antigen 15-3 [CA 15-3] levels in breast carcinoma patients. We also investigated the relationship between anatomical bone type and its effect on tumor marker levels. The study was consisted of retrospective evaluation of 120 bone scans of patients with breast carcinoma admitted to the Nuclear Medicine Department, Medical Faculty, Hacettepe University, Ankara, Turkey between January 2003 and December 2004. The mean age of the patients was 54.7 years. We grouped the results of the bone scans into 3 as normal, equivocal and metastatic. Carcinoembryonic antigen and CA 15-3 levels were recorded from the files of the patients. Upper cut levels of 4.8 U/ml for CEA and 38 U/ml for CA 15-3 was accepted. Metastatic bone areas were distributed according to their anatomical location as long, short, flat, irregular and sesamoid and effect of bone type on tumor marker was investigated. In 16 of the patients, bone scintigraphy revealed metastases. Sixty-one patients had normal scans and in 47 patients metastases could not be ruled out. In patients with metastases, CA 15-3 was elevated in 8 and CEA was higher than the upper limit in 6. For CEA and CA 15-3, the anatomical type of bone has no any effect on serum tumor marker concentration between patients with normal and elevated levels of tumor markers in metastatic patients. Tumor markers are not solely enough in predicting bone metastases. Bone scintigraphy and tumor markers should be both used in management of patients with breast carcinoma. The anatomical type of bone has no any effect on elevation of serum tumor marker concentration

relation between tumor marker Ca 15-3 and metastases in interpectoral lymph nodes in breast cancer patients

We aimed at analyzing the metastatic involvement in interpectoral [Rotter's] lymph nodes [RLN] in relation to tumor marker CA 15-3. The study included 177 female patients undergoing surgery for primary breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to March 2004. In addition to the standard surgical procedure, interpectoral RLNs were removed in all of the patients Levels of the serum tumor marker CA 15-3 was determined prior to surgery. Rotter's lymph nodes were identified in 66.2% of the patients, with metastatic involvement revealed in 18.6% of the RLNs. Metastatic involvement of RLNs in patients with negative axillary lymph nodes was 2.8% and positive in 34.6%. Elevated serum levels of tumor marker CA 15-3 had 22 [12.4%] patients. of 33 Rotter's node-positive patients, 27.3% had elevated serum levels of tumor marker CA 15-3 and in Rotter's node-negative patients only 9% had elevated serum levels of tumor marker CA 15-3, with the level statistically significantly higher in Rotter's positive patients compared to those with negative [or absent] RLNs [chi 2=8.22,P=0.004. Tumor marker CA 15-3 is more frequently elevated in patients with positive RLNs. Elevated values of tumor marker CA 15-3 could be warning for possible positive interpectoral nodes. The removal of the RLNs may be beneficial for patients with [massive] axillary nodal involvement. For axillary node negative patients, sentinel node biopsy could avoid the unnecessary removal of the RLNs.

Clinical significance of cancer antigen, CA 15.3 in breast cancer.

Breast cancer is the leading type of cancer in women. It is commonly accepted that the earlier the detection of the disease, the better the prognosis. Therefore, the present study was undertaken to evaluate the clinical significance of tumour marker CA 15-3 along with Carcinoembryonic antigen (CEA) in India women population. Tumour marker CA 15-3 concentrations reflected the tumour burden in a better way than CEA. However, the use of CEA as an additional conventional marker improved the Clinical efficiency of the marker CA 15-3.

Is epithelial membrane antigen a better prognostic factor than keratin proteins in colorectal carcinoma?: a comparative immunohistochemical study

The heterogeneous nature of tumour antigen expression may require the selection of monoclonal antibodies on an individual tumour to allow its adequate localization. Epithelial Membrane Antigen [EMA] and Cytokeratins [CK] expressions are not previously been compared in colorectal cancer patients. Sections of colorectal cancer [n= 32] were examined by monoclonal antibodies to EMA; CK. In the normal mucosa adjacent to the tumours, EMA was weakly expressed in 8 cases [25%], and negative in 24 cases [75%] recording mean weighted score of 0.43[ +/- 0.84]. CK expression was positive in the normal mucosa in all cases [100%] recording mean weighted score of 10.4 [ +/- 2.01]. This indicates that EMA is more specific marker than CK in colorectal carcinomas [80% and 50% respectively]. All primary colorectal cancers expressed EMA [100%] while 30 of 32 expressed CK [93.7%]. These results suggest that EMA is more sensitive than CK expression for colorectal cancer. The mean weighted score of EMA staining density was 6.4 [ +/- 4.2] in all grades while it recorded 6.8 [ +/- 4.5] for CK staining density. These results showed no significant difference between EMA and CK expression in all grades of differentiation of the tumours, and highly significant differences in their expression in the normal mucosa when compared with that in the malignant tissue [P<0.005]. Regarding tumour staging; the mean weighted score of EMA staining density was 8.57 [ +/- 4.07] in Dukes stage A; it recorded 4.75[ +/- 4.55] in stage B7 and 6.29[ +/- 4.07] in stage B2. The mean weighted score of CK staining density was 4.14 [ +/- 4.33], 5.87 [ +/- 4.35] and 8.35[ +/- 4.22] respectively. There were no significant differences in EMA expression in the different stages of colorectal carcinoma while CK expression in stages A and B1 and stage B2 was significantly different. EMA expression is negatively correlated with the tumour grade of differentiation and stage, while CK expression was negatively correlated with the tumour grade of differentiation and positively correlated with the stage of colorectal cancer. The combinations of monoctonal antibodies directed against distinct tumour - associated antigens such as EMA and CK may overcome the problem of heterogeneity of antigen expression and improve both the immunolocalization and potential for targeted therapy of monoclonal antibodies to patients with colorectal cancer. These findings lead us to recommend the selection of both Cytokeratins and Epithelial Membrane Antigen as prognostic factors in colorectal carcinoma. Thus selecting monoclonal antibodies markers based on tumour biopsies allow improved tumour localization for imaging or therapy in patients with colorectal cancer

Circulating CA 15.3 as a tumor marker in breast cancer patients: an evaluation of CA 15.3 as a tumour measlier in breast cancer

CA 15. 3 is an antigen expressed by human breast carcinoma cells and defined by two monoclonal antibodies; 115 D[8] and DF[3]. We used Enzyme Linked Immunosorbent Assay [ELISA] to determine the antigen levels in plasma of 50 woman divided into 5 groups; 10 healthy women as controls [Group [I]], 10 patients with benign breast diseases [Group [II]], 10 patients with ovarian, endometrial or cervical [non breast cancer] [Group [Ill]], 10 patients with operable mammary carcinoma [Group [IV]] and a further 10 patients with dissiminated breast carcinoma [Group [V]]. Plasma CA 15. 3 level was [13. 1 +/- 3. 28 u/ml] in. group [I], [10 +/- 4. 03 u/ml] in group [II], [16. 3 +/- 4. 97 u/ml] in group [Ill], [21. 2 +/- 5. 94 V/ml] in group [IV] and [69. 7 +/- 5. 57 u/ml] in group [V]. Our results showed that, circulating CA 15. 3 antigen level agreed with the stage of breast cancer and may be regarded as a useful guide in surveillance of breast cancer patients. Despite this still there is 40% of advanced mamary carcinoma patients had CA 15. 3 levels similar to that of normal healthy control and must be regarded as an antigen negative

Compartlve study of CA 15-3 and CEA in breast cancer patients

Serum CA 15-3 and CEA values were determined in 77 patients with breast oancer of different stages, 28 non-malignant breast disease and 36 hedlthy women. Increased -preoperative serum CA 15-3 values [> 30 U ml[-l] were observed in 30%, 75% and 91%, serum CEA values [> 3.5 ng ml[-1]] were observed in 17% 35% and 64% of patients with stage II, III and IV disease respectively. In 86% of patients with a single metastasis and 100% of patients with two or more metastases elevated values for both markers were noted. Only 10% of patients with non-malignant disease had elevated serum CA 15-3, 14% of them had elevated serun CEA and non of normal healthy women had elevated levels for both markers. In the postoperative samples, there was significant reduction in 90% of patients for serum CA 15-3 and CEA. In 66% of patients treated by radical radiotherapy there was a notable reduction in both markers one month later. In 58% of patients with metastatic breast carcinoma treated by combination chemotherapy FAC and CMF [in partial remission], there was a detectable reduction in both markers after eight courses. CEA showed parallel behaviour to CA 15-3., At the, time of recurence elevated serum CA 15-3 values were also observed in patients with normal preoperative values. Increased serum CA 15-3 values preceded the clinical detection of tumour recurrence by up to 11 months. In conclusion it is confirmed that serum CA 15-3 levels had reliable prognostic value in breast cancer, reflected the extent of tumour load, response to treatment and the presence of occult metastasis