Evaluation of Chromogranin a Expression in Serum and Tissues of Breast Cancer Patients

2001 ◽  
Vol 16 (4) ◽  
pp. 268-272 ◽  
Author(s):  
L. Giovanella ◽  
M. Marelli ◽  
L. Ceriani ◽  
G. Giardina ◽  
S. Garancini ◽  
...  

Human chromogranin A (CgA) is a member of the granin family and is widely distributed in large dense core granules of endocrine and neuroendocrine cells. A variety of non-neuroendocrine carcinomas arising in various tissues show patterns of neuroendocrine differentiation. Expression of CgA has been documented in epithelial cells of normal mammary gland as well as in breast cancers, and elevation of serum CgA has been detected in patients with breast cancer. Our study was undertaken to evaluate the relationship between serum CgA levels and neuroendocrine features in breast cancer. In addition, we evaluated the expression of serum CgA in patients affected by breast cancer compared to controls and the relationship between serum CgA and tumor histology, extent of disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266 patients with infiltrating ductal or lobular breast carcinoma and a group of 100 age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3 was 0.06 and 0.34, respectively (χ219.1, p<0.0005). No relationship was found between serum levels of CgA and tumor histology, extent of disease, lymph node status or tumor stage while serum levels of CA 15.3 were strongly correlated with all these variables but tumor histology. No relationship was found between serum levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA-negative patients and was negative in all cases. We also evaluated eight cases of pathologically-proven neuroendocrine breast cancer: only four and two of these showed positive CgA immunostaining and increased serum CgA concentration, respectively. In conclusion, serum CgA assay offers no additional information regarding the presence, the extent and the histology of breast cancer compared to the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or exclude the rare neuroendocrine differentiation of breast cancer. We therefore conclude that CgA is not useful as a serum marker in breast cancer.

2021 ◽  
pp. 1-9
Author(s):  
Parvaneh Yazdanpanah ◽  
Ali Alavianmehr ◽  
Abbas Ghaderi ◽  
Ahmad Monabati ◽  
Mehdi Montazer ◽  
...  

BACKGROUND: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. OBJECTIVES: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). METHODS: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. RESULTS: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. CONCLUSION: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.


1987 ◽  
Vol 73 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Paolo Lissoni ◽  
Franco Paolorossi ◽  
Sandro Barni ◽  
Gabriele Tancini ◽  
Sergio Crispino ◽  
...  

Both prolactin (PRL) and melatonin (MLT) (the most important pineal hormone) have been shown to play a role in regulating breast cancer growth. The present study was carried out to investigate the relationship between PRL and MLT secretions in human breast cancer. Twenty-four women with breast cancer, at clinical stage T1-2 N0-2 M0, were evaluated before and after radical mastectomy. As controls, 14 women who underwent surgery for reasons other than neoplastic disease were included in the study. PRL and MLT serum levels were measured by RIA before and 15 days after surgery. There were no significant differences in mean PRL serum levels between patients and controls; mean MLT serum values were significantly higher in patients than in controls. In no control subject was PRL affected by surgery. In contrast, 13/24 breast cancer women showed high PRL levels after mastectomy; the PRL rise induced by surgery was significantly higher in patients without axillary node involvement. MLT was not affected by mastectomy in 13 patients, whereas it was enhanced in 5 women and decreased in the last 6 cases. No significant correlation was seen between PRL and MLT changes induced by mastectomy. The present study shows that radical mastectomy influences PRL and MLT secretions, however, its clinical significance remains to be established.


1992 ◽  
Vol 7 (4) ◽  
pp. 217-221 ◽  
Author(s):  
C. Zamagni ◽  
A. Martoni ◽  
N. Cacciari ◽  
B. Bellanova ◽  
F. Vecchi ◽  
...  

CA-549 serum levels were assessed in 288 patients, 156 with early breast cancer (after surgery) and 132 with advanced breast cancer. CA-549 was abnormal (> 12 U/ml) in 25/156 patients (16%) without clinical signs of disease after surgery (median 9 U/ml), in 49/60 patients (82%) with disease in progression (P) (median 50 U/ml), in 19/27 patients (70%) with stationary disease (NC) (median 14 U/ml), in 25/33 patients (76%) with partial remission (PR) (median 18 U/ml) and in 4/12 patients (33%) with complete remission (CR) (median 9 U/ml). CA-549 serum levels correlated mainly with the extent of disease and secondarily with the prevalent metastatic site, higher values being observed in patients with visceral involvement (median 32.5 U/ml). CA-549 serum levels were also assessed in 51 patients at the start of treatment and at the time of objective evaluation: the results underline the concordance of CA-549 behavior with the clinical outcome in 71% of the cases. We conclude that CA-549 is a useful marker for monitoring breast cancer patients during the advanced stages of the disease.


1995 ◽  
Vol 10 (2) ◽  
pp. 94-99 ◽  
Author(s):  
M. Torres ◽  
C. Pacheco ◽  
A. Valverde ◽  
A.C. Rebollo ◽  
A. Moral ◽  
...  

The levels of CA 549 and SP2 were measured in 430 subjects: 100 healthy blood donors, 130 patients with benign diseases and 200 postoperative breast cancer patients. In the latter group, the serum levels of CA 15.3, CEA and TPA were also measured. The Kolmogorov-Smirnov, Mann Whitney and McNemar tests were used for statistical analysis. The upper normal limits were established on the basis of the values obtained in the healthy blood donors group, the benign diseases group and R.O.C. analysis of the breast cancer group. They were: CA 549 = 13 U/ml, SP2 = 14 U/ml, CA 15.3 = 35 U/ml, CEA = 5 ng/ml and TPA = 110 U/ml. The sensitivity, specificity and accuracy in the breast cancer group were, respectively: CA 549 = 78.1%, 97.1% and 88%; SP2 = 21.9%, 90.4% and 57.5%; CEA = 66.7%, 95.2% and 81.5%; CA 15.3 = 80.2%, 98.1% and 89.5%, and TPA = 73.9%, 78.8% and 76.5%. Statistical analysis showed significant differences only between CA 15.3, the marker which gave the best results, and SP2 (p<0.001). There were no significant differences with the association of two or three tumor markers.


1989 ◽  
Vol 4 (4) ◽  
pp. 207-214 ◽  
Author(s):  
F. Safi ◽  
I. Kohler ◽  
E. Röttinger ◽  
P. Suhr ◽  
H. G. Beger

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.


1993 ◽  
Vol 8 (4) ◽  
pp. 208-214
Author(s):  
G.C. Yadav ◽  
A. Rao ◽  
M.M. Motawy ◽  
N. Safadi ◽  
M. Jameel Ahmed

Serum levels of breast carcinoma antigen (CA 15.3) and urinary calcium excretion (UCa) were determined in 73 patients with breast cancer: 36 without bone metastases (stage I-IV) and 37 with bone metastases. The patients in the latter group were further investigated at 2,4 and 6 months from the start of treatment. Both markers showed significant elevations in the group with bone metastases (CA 15.3: P = 1.0×10–6, UCa: P = 8.6×10–9). The bone metastasis index (BMI), which represents the combination of the markers, had better diagnostic efficacy (90%) than CA 15.3 alone (84%) or UCa alone (82%). During treatment of bone metastasis, the longitudinal levels of the markers showed a highly significant association with the therapeutic response assessed by the UICC criteria. For identifying progression of disease, the diagnostic efficacy of CA 15.3, UCa and a combination of both, the so-called Biochemical Index of Response (BIR), was 65%, 70% and 79%, respectively, at two months and 89%, 84% and 92% at four months. Application of the tandem, CA 15.3 with UCa, was very useful for the detection of bone metastases and the prediction of response to therapy.


2005 ◽  
Vol 91 (6) ◽  
pp. 522-530 ◽  
Author(s):  
Javier Martínez-Trufero ◽  
Abigail Ruíz de Lobera ◽  
Juan Lao ◽  
Teresa Puértolas ◽  
Angel Artal-Cortés ◽  
...  

Background Locally advanced breast cancer (LABC) represents a heterogeneous subgroup of breast cancer with an often dismal outcome. Identifying prognostic factors has acquired great significance for the selection of optimal treatment in individual patients. Methods Between January 1993 and December 1997, 103 patients were treated in our institution with multimodality treatment consisting of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and radiotherapy; tamoxifen was added in hormone receptor-positive cases. In the search for prognostic factors well-established parameters (clinical, pathological and treatment-related) as well as new features with potential value (c-erbB-2, baseline serum levels of CA 15.3 and CEA) were included in the univariate and multivariate analysis. Results At a median follow-up of 92 months (range, 8-130), the estimated five-year cancer-specific overall survival (OS) and disease-free survival (DFS) were 71.34% and 57.7%, respectively. Among the 22 different variables studied, only 10 were significantly correlated with OS and DFS. In multivariate analysis five retained independent prognostic value for both OS and DFS: tumor grade, serum markers, features of inflammatory breast cancer (IBC), response to neoadjuvant chemotherapy and lymph node status. With cutoff values of 35 U/mL for CA 15.3 and 5 ng/mL for CEA, the probability of five-year OS (Cox hazard ratio 3.91, P = 0.0009) and DFS (Cox hazard ratio 2.40, P = 0.02) decreased from 78% to 52% and from 68% to 47%, respectively, when at least one of these markers was abnormal. Conclusions Baseline serum levels of CEA and CA 15.3 emerged from this study as strong independent predictors of outcome in LABC, whose value adds to other established prognostic factors such as postoperative nodal status, IBC, histological grade and response to neoadjuvant chemotherapy.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Aneta Cymbaluk-Płoska ◽  
Anita Chudecka-Głaz ◽  
Ewa Pius-Sadowska ◽  
Agnieszka Sompolska-Rzechuła ◽  
Karolina Chudecka ◽  
...  

The objectives of the study were to assess the relationship between the serum levels of MMP-9 and NGAL and the clinical staging and histopathological grade of the tumor. Lipocalin-2/NGAL and MMP-9 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation, Austin, TX, USA). The AUC values for NGAL and MMP-9 were 0.9 and 0.78, respectively. The diagnostic potential of NGAL and MMP-9 in differentiating high-stage (FIGO III and IV) and low-stage (FIGO I and II) cancer and predicting the cell differentiation grade (G1 versus G3) on the basis of the analyses of AUC values was determined to be 0.91 and 0.79 for NGAL and 0.82 and 0.84 for MMP-9, respectively. Multifactorial logistic regression analysis in the final method revealed that NGAL and MMP-9 variables were independent of the endometrial cancer risk. OR values for NGAL and MMP-9 were 1.23 (95% CI 1.421–3.27; p=0.034) and 1.09 (95% CI: 1.38–4.12; p=0.026), respectively. The NGAL/MMP-9 complex may be useful in the assessment of tumor stage before surgical treatment.


1995 ◽  
Vol 10 (1) ◽  
pp. 24-29 ◽  
Author(s):  
L. Rodríguez De Paterna ◽  
F. Arnaiz ◽  
J. Estenoz ◽  
B. Ortuño ◽  
E. Lanzós

Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of 499 breast cancer patients. Studies included three different groups of women: 82 blood donors free of disease, 42 patients with non-malignant breast diseases and 499 breast cancer patients. After the determinaion of cut-off values, serum levels of tumor markers did not show significant elevations in benign breast diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%) was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least sensitive and effective marker. The combined use of markers was evaluated by step-wise logistic regression analysis. The regression coefficients showed that CA 15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection of possible metastases during follow-up. Finally, we studied the relationship between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.


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