Molecular forms of prostate-specific antigen in the serum of women with benign and malignant breast diseases

Abstract

Summary Using a highly sensitive immunofluorometric procedure, we measured the total prostate-specific antigen (PSA) concentration in 632 sera obtained from female blood donors and women with idiopathic hirsutism, breast cancer or benign breast diseases. A total of 50 sera with total PSA> 15 ng 1-' were fractionated by high-performance liquid chromatography (HPLC) in order to resolve the two immunoreactive molecular forms, i.e. free PSA (approximately 30 kDa) and PSA bound to a1-antichymotrypsin (PSA-ACT, 100 kDa). We found that breast cancer patients have presurgical serum total PSA levels similar to those of blood donors. Total serum PSA concentration decreases with age in women with idiopathic hirsutism, in cancer patients and in patients with benign breast diseases. The major molecular form of PSA in the serum of all normal and hirsute women (n = 15) is PSA bound to the proteinase inhibitor a,-antichymotrypsin. The major molecular form in 44% of presurgical cancer patient sera-is free PSA. A total of 58% of benign breast disease patients also have in their serum mainly free PSA. We conclude that about half the patients with breast cancer or benign breast diseases have free PSA as the major molecular form in their serum, whereas patients without breast pathologies (normal blood donors, idiopathic hirsutism) have PSA bound to a1-antichymotrypsin as the major molecular form. The ratio of PSA/PSA-ACT may have value as a simple biochemical test for diagnosis of breast pathologies including breast cancer.

Measurement of serum total and free prostate-specific antigen in women with colorectal carcinoma

“…The cut-off value in breast cancer diagnosis for total PSA is 30 ng ml 71 (Borchert et al, 1997;Romppanen et al, 1999) which is 10 times lower than the value we found. This discrimination may be due to the difference in the sensitivities of PSA assays.…”

“…It has been shown that serum total PSA levels in women with breast cancer were significantly higher than healthy women, and in women with breast cysts were significantly higher than women with breast cancer and serum free PSA levels in breast cancer patients were significantly higher than healthy women (Black et al, 2000). Another study revealed serum total PSA concentrations to be significantly lower in women with breast cancer than women with benign breast disease and no significant difference was found between cancer patients and normal women; free PSA levels showed no difference in the groups (Borchert et al, 1997). In another study, no significant difference in serum total PSA levels was found between breast cancer patients and women with benign breast disease or healthy women (Romppanen et al, 1999).…”

“…Studies conducted in women with breast cancer revealed contrary results. It was demonstrated that 44% of women with breast cancer and 58% of women with benign breast disease had serum free PSA as the major molecular form, whereas normal women had PSA bound to a 1 -antichymotripsin as the major molecular form, and it was suggested that the ratio of free PSA/bound PSA might have value for diagnosis of breast diseases including breast cancer (Borchert et al, 1997). In another study (Black et al, 2000), it was demonstrated that the percentage (20%) of breast cancer patients with free PSA as the predominant molecular form (450% of total PSA) in serum was significantly higher than that of healthy women (3%) or women with benign breast disease (4%), and it was stated that although free PSA as the predominant molecular form has high specificity (96%), its clinical utility is limited due to low sensitivity (20%).…”

“…In one study serum total PSA levels were found to decrease significantly with ageing in both healthy women and women with breast cancer (Romppanen et al, 1999). However, in another study no significant correlation was found between serum total PSA levels and age in normal women while a negative correlation was demonstrated in women with breast cancer (Borchert et al, 1997). As in the explanation of the decrease of PSA expression with ageing in breast cancer tissue (Yu et al, 1994a), the decrease in PSA production with ageing might be due to the decrease of ovarian hormones which mediate PSA production by binding to the steroid receptors found in colorectal cancer tissue.…”

“…Recently, molecular forms of PSA (a 1 -antichymotripsin-bound PSA and free PSA) have been investigated in the sera of women with benign and malignant breast diseases and it has been reported that existence of free PSA as the major molecular form may be of diagnostic importance in female breast cancer (Borchert et al, 1997;Black et al, 2000).…”