The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast

Black, Margot H.; Diamandis, Eleftherios P.

doi:10.1023/a:1006380306781

Cited by 94 publications

(72 citation statements)

References 124 publications

(166 reference statements)

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“…With the availability of highly sensitive techniques, it has become apparent that both hK2 and hK3 are also expressed at lower levels in many other tissues, including breast, thyroid, and salivary glands (Yu and Diamandis 1995;Black and Diamandis 2000;Magklara et al 2000). The expression of hK10 mainly by glandular epithelia suggests that it is secreted.…”

Section: Discussionmentioning

confidence: 99%

Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

Petraki

Karavana

Luo

et al. 2002

J Histochem Cytochem.

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The normal epithelial cell-specific 1 (NES1) gene (official name kallikrein gene 10, KLK10) was recently cloned and encodes for a putative secreted serine protease (human kallikrein 10, hK10). Several studies have confirmed that hK10 shares many similarities with the other kallikrein members at the DNA, mRNA, and protein levels. The enzyme was found in biological fluids, tissue extracts, and serum. Here we report the first detailed immunohistochemical (IHC) localization of hK10 in normal human tissues. We used the streptavidin-biotin method with two hK10-specific antibodies, a polyclonal rabbit and a monoclonal mouse antibody, developed in house. We analyzed 184 paraffin blocks from archival, current, and autopsy material, prepared from almost every normal human tissue. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. Previously, we reported the expression of another novel human kallikrein, hK6, by using similar techniques. The IHC expression of hK10 was generally cytoplasmic and not organ-specific. A variety of normal human tissues expressed the protein. Glandular epithelia constituted the main immunoexpression sites, with representative organs being the breast, prostate, kidney, epididymis, endometrium, fallopian tubes, gastrointestinal tract, bronchus, salivary glands, bile ducts, and gallbladder. The choroid plexus epithelium, the peripheral nerves, and some neuroendocrine organs (including the islets of Langerhans, cells of the adenohypophysis, the adrenal medulla, and Leydig cells) expressed the protein strongly and diffusely. The spermatic epithelium of the testis expressed the protein moderately. A characteristic immunostaining was observed in Hassall's corpuscles of the thymus, oxyphilic cells of the thyroid and parathyroid glands, and chondrocytes. Comparing these results with those of hK6, we observed that both kallikreins had a similar IHC expression pattern.

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Section: Discussionmentioning

confidence: 99%

Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

Petraki

Karavana

Luo

et al. 2002

J Histochem Cytochem.

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“…PSA is the best screening marker available for prostate cancer (13). PSA is now known to exist in nonprostatic tissues, including the breast, lung, ovary, uterus, and pancreas (15)(16)(17). We have determined in a small cohort that PSA levels in NAF are inversely associated with breast cancer (18), suggesting that PSA may be a useful marker to screen women at risk for the disease.…”

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confidence: 94%

Circulating testosterone and prostate-specific antigen in nipple aspirate fluid and tissue are associated with breast cancer.

Sauter

Tichansky

Chervoneva

et al. 2002

Environ Health Perspect

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Preliminary evidence has associated testosterone and prostate-specific antigen (PSA) with breast cancer. Our objective was to determine whether a) testosterone levels in nipple aspirate fluid (NAF), serum, or breast tissue are associated with breast cancer; b) testosterone levels in serum are associated with levels in NAF; c) PSA in NAF, serum, or breast tissue is associated with breast cancer; and d) serum PSA is associated with NAF PSA levels. We obtained 342 NAF specimens from 171 women by means of a modified breast pump. Additionally, we collected 201 blood samples from 99 women and 51 tissue samples from 41 subjects who underwent surgical resection for suspected disease. Women currently using birth control pills or hormone replacement therapy were excluded from the study. Controlling for age and menopausal status, serum testosterone was significantly increased in women with breast cancer (p = 0.002). NAF and serum testosterone levels were not associated. Neither NAF nor tissue testosterone was associated with breast cancer. Controlling for menopausal status and age, NAF PSA was significantly decreased in women with breast cancer (p < 0.001). We did not find serum PSA to be associated with breast cancer, although we found an indication that, in postmenopausal women, its levels were lower in women with cancer. Serum PSA was associated with NAF PSA in postmenopausal women (p < 0.001). PSA levels in cancerous tissue were significantly lower than in benign breast specimens from subjects without cancer (p = 0.011), whereas levels of PSA in histologically benign specimens from subjects with cancer were intermediate. Our results suggest that serum testosterone is increased and NAF PSA is decreased in women with breast cancer, with PSA expression being higher in normal than in cancerous breast tissues. NAF and serum PSA levels in postmenopausal women are correlated, suggesting that as laboratory assessment of PSA becomes more sensitive, serum PSA may become useful in identifying women with breast cancer.

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“…Prostate-specific antigen (PSA, hK3), a member of this family, is an established tumour marker for prostate cancer (Barry, 2001). Prostate-specific antigen SA was recently found to be expressed in the female breast and might have a prognostic value in breast cancer (Black and Diamandis, 2000). Furthermore, other kallikreins were also found to have prognostic value in breast and other endocrine malignancies (Liu et al, 1996;Tanimoto et al, 1999;Yousef et al, 2000a;Benson et al, 2002;Diamandis and Yousef, 2002;Diamandis, 2002a, 2003;Diamandis et al, 2003;Luo et al, 2003).…”

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confidence: 99%

Kallikrein gene downregulation in breast cancer

et al. 2004

Br J Cancer

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Recent evidence suggests that many members of the human kallikrein gene family are differentially regulated in breast cancer and other endocrine-related malignancies. In this study, we utilised the serial analysis of gene expression (SAGE) and expressed sequence tag (EST) databases of the Cancer Genome Anatomy Project (CGAP) to perform in silico analyses of the expression pattern of the 15 human kallikrein genes in normal and cancerous breast tissues and cell lines using different analytical tools such as Virtual Northern blotting, Digital Differential Display and X-profiler. Our results indicate that at least four kallikrein genes (KLK5, 6, 8, 10) are downregulated in breast cancer. Probing eight normal and 24 breast cancer SAGE libraries with gene-specific tags for each of the above kallikreins indicated moderate-to-high expression densities in normal breast (27 -319 tags per million; tpm, in two to five out of eight libraries), compared to no or low expression (0 -34 tpm in zero to two libraries out of 24) in breast cancer. These data were verified by screening the EST databases, where all mRNA clones isolated for these genes, except for one in each, were from normal breast libraries, with no clones detected from breast cancer tissues or cell lines (with the exception of KLK8). X-profiler comparison of two pools of normal and breast cancer libraries further verified the presence of significant downregulation of expression levels of 4 of the kallikreins genes (KLK5, 6, 10, 12). We experimentally verified the downregulation of these four kallikreins (KLK5, 6, 8, 10 and 12) by RT -PCR analysis.

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The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast

Cited by 94 publications

References 124 publications

Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

Circulating testosterone and prostate-specific antigen in nipple aspirate fluid and tissue are associated with breast cancer.

Kallikrein gene downregulation in breast cancer

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