• Users Online: 1008
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Browse Articles Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 6  |  Issue : 1  |  Page : 15

Is serum prostate-specific antigen a diagnostic marker for benign and malignant breast tumors in women?


1 Department of Surgery, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Brain and Spinal Cord Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Pathology, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Surgery, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission21-Sep-2014
Date of Acceptance15-Dec-2014
Date of Web Publication20-Feb-2015

Correspondence Address:
Alireza Abdollahi
Central Laboratory, Keshavarz Blvd., Imam Hospitals Complex, Tehran
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2008-7802.151824

Rights and Permissions
  Abstract 

Background: Breast cancer is the most common cancer in women. Prostate-specific antigen (PSA) is a marker of prostate gland malignancy, which has been considered in cases with breast cancer in recent years. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions.
Methods: In this case-control study, ninety women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. Total and free PSA levels along with Histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers recorded for all cases. Total and free PSA levels were assessed after treatment in cases with malignant masses.
Results: Total and free PSA levels were significantly higher in cases with malignant masses. The best cut-off point for total PSA to differentiate benign and malignant masses was 0.31 with sensitivity and specificity of 100%, 100% (area under the curve [AUC] =1, P < 0.001) and the best cut-off point for free PSA to differentiate benign and malignant masses was 0.19 with sensitivity and specificity of 100% and 100% (AUC = 1, P < 0.001). After treatment, mean free PSA level was significantly lower than free PSA before treatment (0.23 ± 0.1 vs. 0.3 ± 0.08, P < 0.001).
Conclusions: Serum PSA level could be applied for differentiating benign and malignant breast masses.

Keywords: Breast, diagnosis, prostrate-specific antigen


How to cite this article:
Emami Razavi SH, Ghajarzadeh M, Abdollahi A, Shoar S, Omranipour R. Is serum prostate-specific antigen a diagnostic marker for benign and malignant breast tumors in women?. Int J Prev Med 2015;6:15

How to cite this URL:
Emami Razavi SH, Ghajarzadeh M, Abdollahi A, Shoar S, Omranipour R. Is serum prostate-specific antigen a diagnostic marker for benign and malignant breast tumors in women?. Int J Prev Med [serial online] 2015 [cited 2020 Jun 1];6:15. Available from: http://www.ijpvmjournal.net/text.asp?2015/6/1/15/151824


  Introduction Top


Breast cancer is the most common cancer in women equally in developing and developed countries. [1] Different factors such as high body mass index, advanced age, family history of breast cancer, a long menstrual history, use of oral contraceptives, exposure to radiation, no childbearing or giving birth to the first child after age 30 are among possible risk factors for breast cancer. [2] Death due to breast cancer has been reduced according to screening approaches like mamography. [3] To differentiate benign and malignant lesions, lesion biopsies, ultrasound assessment, and mammography evaluation are diagnostic methods. [4]

Prostrate-specific antigen (PSA) is a marker of prostate gland malignancy screening test. [5] It is a member of the kallikrein family that is known as human kallikrein 3. [5] Except prostate gland, previous studies showed that it could be present in breast, lung, ovary, uterus, and pancreas tissues. [6],[7]

In a previous study conducted by Black et al., they investigated that sensitivities and specificities of total and free PSA levels for differentiating benign and malignant breast lesions are 57% and 36%, 25% and 72%. [8] However, there limited number of studies evaluating serum PSA level in cases with breast cancer. The goal of this study was to determine total and free PSA levels in cases with malignant and benign breast lesions.


  Methods Top


Study design and participants

In this case-control study, 90 women with histological proved malignant breast masses and 90 with benign breast masses were enrolled. The study conducted in Imam Hospital (affiliated hospital of the Tehran University of Medical Sciences) in 2012. Project number 88-03-30-8920.

Histological grade and conditions of vascular and perinural invasion, status of hormonal tumor receptors, immune-histo-chemistry markers including p53, Ki67 and Her2 were determined and registered prior to any treatment. Total and free PSA levels were assessed after treatment in cases with malignant masses. Pregnant women, those with autoimmune diseases and women who had taken corticosteroids during the last month were excluded.

All cases asked to fill informed consent form before study entrance. The study had been approved by local ethics committee.

Procedure and measurements and variables assessment

For each case, 5 cc venous blood was taken, centrifuged at 3,000 g for 10-15 min. Total and free PSA levels were assessed by sandwich chemiluminescence immunoassay technique.

Diasorin Deutschland GmbH (LIAISON) kit was used for total PSA while Diasorin S.P.A, Italy (LIAISON) kit was applied for free PSA analysis.

A method for the quantitative determination of PSA was a sandwich chemiluminescence immunoassay. A specific mouse monoclonal antibody was coated on the magnetic particles (solid phase). Another monoclonal antibody was linked to an isoluminol derivative (isoluminol-antibody conjugate). Free and antichymotrypsin-complex-bound PSA were detected equimolarly. During the first incubation, PSA present in the calibrators, samples or controls bounded to the solid phase monoclonal antibody, and subsequently after a washing step in the second incubation the antibody conjugate reacted with the PSA already bound to the solid phase. After incubation, the unbound material was removed with a wash cycle. Subsequently, the starter reagents were added and a flash chemiluminescence reaction was thus induced, the light signal, and hence the amount of isoluminol-antibody conjugate, was measured by a photomultiplier as relative light units, indicative of PSA concentration present in calibrators samples or controls.

Analytical sensitivity for t-PSA is defined as the minimum detectable dose distinguishable from zero by two standard deviations (SDs). The detection limit is <0.04 ng/ml. The assay trueness was checked by the dilution and recovery tests. Analytical sensitivity for f-PSA is defined as the minimum detectable dose distinguishable from zero by two SDs. The detection limit is <0.09 ng/ml. The functional sensitivity (defined as the lowest analyte concentration that can be determined with an inter-assay coefficient of variation <20%) is <0.15 ng/ml.

Six months after treatment, total and free PSA levels evaluated in cases with malignant masses.

Statistical analysis

All data were analyzed using SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). Data were presented as mean ± SD for continuous or frequencies for categorical variables. Independent sample t-test and paired sample t-test were used to compare continuous variables. Receiver operating characteristic curve was used to determine optimal cut-off values of total and free PSA. Area under the curve (AUC) calculated.

P < 0.05 was considered as significant.


  Results Top


A total of 180 women with breast tumors were enrolled in this study, 90 patients with malignant breast cancers and 90 patients with benign breast masses. Women with benign tumors aged between 28 years and 63 years with an average age of 38 ± 4 years while women with breast cancer were aged between 36 years and 84 years with an average age of 61 ± 3 years old. Forty-seven of the patients (53.2%) had positive family history for breast cancer. [Table 1] shows histological types of benign masses.
Table 1: Demographic and pathologic findings in patients


Click here to view


Total and free PSA levels were significantly higher in cases with malignant masses [Table 2].
Table 2: Comparison of total PSA and free PSA serum levels in women with benign masses and malignant tumors before surgery and 6 months after treatment


Click here to view


The best cut-off point for total PSA to differentiate benign and malignant masses was 0.31 with sensitivity and specificity of 100%, 100% (AUC = 1, P < 0.001) [Figure 1].
Figure 1: ROC curve for PSA measure

Click here to view


The best cut-off point for free PSA to differentiate benign and malignant masses was 0.19 with sensitivity and specificity of 100% and 100% (AUC = 1, P < 0.001) [Figure 2].
Figure 2: ROC curve for free PSA measure

Click here to view


After treatment mean total PSA level was significantly higher than total PSA level was significantly higher than total PSA level before treatment (0.88 ± 0.3 vs. 0.77 ± 0.25, P < 0.001) while mean free PSA level was significantly lower than free PSA before treatment (0.23 ± 0.1 vs. 0.3 ± 0.08, P < 0.001).


  Discussion Top


The result of the current study showed that total and free PSA levels are significantly higher in women with malignant breast masses compared with women who had benign breast masses. We also found that free PSA level was significantly higher before surgery than postsurgery in cases with breast masses. These findings are against the findings of Black et al. [8]

They evaluated total and free PSA levels in women with breast cancer, breast cysts and also healthy controls. They investigated that patients with breast cancer had higher total PSA levels before surgery than after surgery and patients with breast cysts had significantly higher levels of total PSA than presurgical breast cancer patients.

In a recent study, Mashkoor et al. evaluated total and free PSA levels in women with breast cancer and healthy subjects. [9] They found that both forms of PSA were significantly higher in patients with breast cancer. Furthermore, after surgery both markers decreased significantly which is against our finding and compatible with Dash et al. finding. Dash et al. measured serum total and free PSA levels in cases with malignant and benign masses and healthy subjects. [10] Their results showed that total and free PSA levels were significantly different between cases either benign or malignant masses versus controls, but total and free PSA levels were not significantly different between patients with benign and malignant masses.

Prostrate-specific antigen is a well-established serum tumor marker for diagnosis and postsurgery follow-up for prostate cancer. Normally, it liquefies the sperm-entrapping seminal coagulum after ejaculation. [11] The name PSA reflects the idea that the expression of this protein is restricted to prostate a gland. Recently, it has been showed that PSA could be present in breast, lung, ovary, uterus, and pancreas tissues. [6],[7] Previous studies showed rise in total and free PSA levels in women with breast masses in comparison with healthy subjects. This could suggest hormonal imbalance in these cases which leads to the expression of genes that are normally controlled by hormones and up-regulated by androgens and progesterone. [12],[13] Literatures show that there is a positive correlation between PSA and testosterone levels in patients with breast cancer confirms the role of androgens on expression of PSA gene. [10],[13],[14]

In postsurgical assessment, we only found that free PSA level decreased and total PSA level increased. This is against findings of previous studies. In prior studies, both total and PSA levels decreased significantly after breast tumor removal, which shows the role of breast tumors in PSA production. [8],[15]

Our study had some limitation. First, we did not assess testosterone in enrolled cases, and we did not include healthy subjects. Multicentric studies with a comprehensive evaluation of patients with benign and malignant masses along with healthy subjects are recommended.


  Conclusions Top


Serum PSA level could be applied for differentiating benign and malignant breast masses.

 
  References Top

1.
Yadollahie M, Simi A, Habibzadeh F, Ghashghaiee RT, Karimi S, Behzadi P, et al. Knowledge of and attitudes toward breast self-examination in Iranian women: A multi-center study. Asian Pac J Cancer Prev 2011;12:1917-24.  Back to cited text no. 1
    
2.
Dündar PE, Ozmen D, Oztürk B, Haspolat G, Akyildiz F, Coban S, et al. The knowledge and attitudes of breast self-examination and mammography in a group of women in a rural area in western Turkey. BMC Cancer 2006;6:43.  Back to cited text no. 2
    
3.
Swedish Organised Service Screening Evaluation Group. Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data. Cancer Epidemiol Biomarkers Prev 2006;15:45-51.  Back to cited text no. 3
    
4.
Shiraishi A. Current state of digital mammography. Breast Cancer 2008;15:194-9.  Back to cited text no. 4
    
5.
Diamandis EP. Prostate-specific antigen: Its usefulness in clinical medicine. Trends Endocrinol Metab 1998;9:310-6.  Back to cited text no. 5
    
6.
Diamandis EP, Yu H. New biological functions of prostate-specific antigen? J Clin Endocrinol Metab 1995;80:1515-7.  Back to cited text no. 6
    
7.
Black MH, Diamandis EP. The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast. Breast Cancer Res Treat 2000;59:1-14.  Back to cited text no. 7
    
8.
Black MH, Giai M, Ponzone R, Sismondi P, Yu H, Diamandis EP. Serum total and free prostate-specific antigen for breast cancer diagnosis in women. Clin Cancer Res 2000;6:467-73.  Back to cited text no. 8
    
9.
Mashkoor FC, Al-Asadi JN, Al-Naama LM. Serum level of prostate-specific antigen (PSA) in women with breast cancer. Cancer Epidemiol 2013;37:613-8.  Back to cited text no. 9
    
10.
Dash P, Pati S, Mangaraj M, Sahu PK, Mohapatra PC. Serum total PSA and free PSA in breast tumors. Indian J Clin Biochem 2011;26:182-6.  Back to cited text no. 10
    
11.
Lilja H, Oldbring J, Rannevik G, Laurell CB. Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. J Clin Invest 1987;80:281-5.  Back to cited text no. 11
    
12.
Zarghami N, Grass L, Diamandis EP. Steroid hormone regulation of prostate-specific antigen gene expression in breast cancer. Br J Cancer 1997;75:579-88.  Back to cited text no. 12
    
13.
Magklara A, Grass L, Diamandis EP. Differential steroid hormone regulation of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) in breast cancer cell lines. Breast Cancer Res Treat 2000;59:263-70.  Back to cited text no. 13
    
14.
Melegos DN, Yu H, Ashok M, Wang C, Stanczyk F, Diamandis EP. Prostate-specific antigen in female serum, a potential new marker of androgen excess. J Clin Endocrinol Metab 1997;82:777-80.  Back to cited text no. 14
    
15.
Hautmann S, Huland E, Grupp C, Haese A, Huland H. Super-sensitive prostate-specific antigen (PSA) in serum of women with benign breast disease or breast cancer. Anticancer Res 2000;20:2151-4.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]


This article has been cited by
1 PROSTATE-SPECIFIC ANTIGEN AND ITS MOLECULAR FORMS IN BLOOD SERUM OF HEALTHY WOMEN AND WOMEN WITH BREAST DISEASE
N. S. Sergeeva,I. I. Alentov,D. R. Ortabaeva,N. V. Marshutina,A. D. Zikiryahodzhaev,A. D. Kaprin
Siberian journal of oncology. 2020; 18(6): 96
[Pubmed] | [DOI]
2 Prostate-Specific Antigen as a Marker of Hyperandrogenism in Women and Its Implications for Antidoping
Natasha Musrap,Eleftherios P Diamandis
Clinical Chemistry. 2016; 62(8): 1066
[Pubmed] | [DOI]
3 On-Chip Mass Spectrometry-Based Immunoassay as a Tool for the Detection of Molecular Species from Prostate-Specific Antigen in Female Serum
Sanja Goc,Miroslava Jankovic
Analytical Letters. 2016; 49(18): 2943
[Pubmed] | [DOI]
4 Free/Total Serum Prostate-Specific Antigen Ratio in Women with Colorectal Cancer Has Prognostic Significance
Nüvit Duraker,Zeynep Civelek Çaynak,Didem Can Trabulus
Journal of Gastrointestinal Cancer. 2016;
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Methods
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1760    
    Printed42    
    Emailed0    
    PDF Downloaded174    
    Comments [Add]    
    Cited by others 4    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]