Prognostic and diagnostic role of PSA immunohistochemistry: A tissue microarray study on 21,000 normal and cancerous tissues

Our plain-English summary of Prognostic and diagnostic role of PSA immunohistochemistry: A tissue microarray study on 21,000 normal and cancerous tissues, by S. Bonk, M. Kluth, C. Hube-Magg, et al (Oncotarget, 2019).

The study

• Authors: S. Bonk, M. Kluth, C. Hube-Magg, A. Polonski, G. Soekeland, G. Makropidi-Fraune, C. Möller-Koop, M. Witt, A.M. Luebke, A. Hinsch, E. Burandt, S. Steurer, T.S. Clauditz, T. Schlomm, D. Perez, M. Graefen, H. Heinzer, H. Huland, J.R. Izbicki, W. Wilczak, S. Minner, G. Sauter, R. Simon
• Journal: Oncotarget
• Published: 2019;10(52):5439-5453
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

To assess the prognostic and diagnostic utility of PSA immunostaining, tissue microarrays containing 17,747 prostate cancers, 3,442 other tumors from 82 different (sub) types and 608 normal tissues were analyzed at two different antibody concentrations (1:100 and 1:800). In normal tissues, PSA expression was limited to prostate epithelial cells. In prostate cancers, PSA staining was seen in 99.9-100% (1:800-1:100) primary tumors, 98.7-99.7% of advanced recurrent cancers, in 84.6-91.4% castration resistant cancers, and in 7.7-18.8% of 16 small cell carcinomas. Among extraprostatic tumors, PSA stained positive in 0-3 (1:800-1:100) of 19 osteosarcomas, 1-2 of 34 ovarian cancers, 0-2 of 35 malignant mesotheliomas, 0-1 of 21 thyroid gland carcinomas and 0-1 of 26 large cell lung cancers. Reduced staining intensity and loss of apical staining were strongly linked to unfavorable tumor phenotype and poor prognosis (p < 0.0001 each). This was all the more the case if a combined "PSA pattern score" was built from staining intensity and pattern. The prognostic impact of the "PSA pattern score" was independent of established pre- and postoperative clinico-pathological prognostic features. In conclusion, PSA immunostaining is a strong prognostic parameter in prostate cancer and has high specificity for prostate cancer at a wide range of antibody dilutions.

In plain English

This Hamburg laboratory study was about prostate cancer, not asbestos; malignant mesothelioma was one of many tumor types tested. The authors stained archived tissue with an antibody against prostate specific antigen (PSA) at strengths of 1:100 and 1:800. Samples came from 17,747 men operated on for prostate cancer between 1992 and 2015, 316 patients with recurrent or advanced prostate cancer, 3,442 other tumors of 82 types, and 608 normal tissues. Of normal tissues, only prostate stained. Nearly all prostate cancers stained (99.66% at 1:800); only 1 of 13 prostate small cell carcinomas did. Outside the prostate, one ovarian cancer stained at 1:800. At 1:100, 9 stained, including 2 malignant mesotheliomas (of 2,845 per the text, 2,825 per its table). In prostate cancer, weaker staining and loss of apical (cell-top) predominance of staining were linked to unfavorable tumor features and prognosis; a combined score of both predicted prognosis independently of standard factors. The authors concluded that PSA is a strong prognostic marker and found no evidence of a significant specificity problem. They noted staining depends on reagents and methods.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (immunohistochemistry) study of archived tissue samples on tissue microarrays, with a retrospective analysis of patient outcome in prostate cancer
• Who was studied: Tissue from 17,747 prostate cancer patients operated on between 1992 and 2015 at the University Medical Center Hamburg-Eppendorf (follow-up available for 14,667), 316 patients with recurrent or advanced prostate cancer, 3,442 samples from 82 other tumor types and subtypes (including malignant mesothelioma), and 608 normal tissue samples (8 each of 76 tissue types)
• Exposure: No asbestos or other exposure was studied. Tissues were stained with a mouse monoclonal PSA antibody (DIA-PSA, clone HAM18) at dilutions of 1:100 and 1:800.
• Main results:
  • In normal tissues, all eight normal prostate samples were PSA positive, and no other normal tissue showed PSA staining.
  • In prostate cancers, 99.9% of Gleason 3+4 or lower cancers stained at 1:800. Only 1 of 13 small cell neuroendocrine carcinomas of the prostate showed PSA.
  • In cancers from outside the prostate, only one endometroid ovarian cancer stained at 1:800. At 1:100, 9 extraprostatic cancers stained, including 2 malignant mesotheliomas. The text gives the denominator as 2,845 (0.3%), while Table 2 lists 2,825 analyzable non-prostate cancers at 1:100 (0.32% positive).
  • For malignant mesothelioma, Table 2 lists 37 analyzable samples at 1:800 with 0% PSA positive, and 39 analyzable at 1:100 with 5.71% PSA positive.
  • In prostate cancer, reduced PSA staining intensity and loss of apical predominance of staining were linked to unfavorable tumor phenotype and prognosis.
  • A combined 'PSA pattern score' (intensity plus pattern) predicted prognosis in prostate cancer independently of established prognostic factors.
• The authors' conclusion: The authors concluded that PSA expression is a strong prognostic parameter in prostate cancer. They also concluded that their testing of non-prostate tumors did not show a significant specificity problem, since PSA staining outside the prostate was rare and typically weak.
• Limitations the authors state:
  • The authors stated that immunohistochemistry has inherent limitations: staining intensity depends on the reagents and protocols used.
  • The authors stated that the chosen procedure sets a limited range of measurable expression: below it everything reads negative, and above it everything reads strongly positive.

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Carcinoma, Ovarian Cancer, Mesothelioma, Lung Cancer, Prognosis.

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