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p16 Expression in Prostate Cancer and Nonmalignant Lesions: Novel Findings and Review of the Literature

p16 Expression in Prostate Cancer and Nonmalignant Lesions: Novel Findings and Review of the... Background: Prostatic specimens occasionally may contain proliferative foci of the small atypical acini that display some but not all features of prostate carcinoma. p504s is the only prostatic cancer (PC)-specific marker that, in combination with basal cell markers, help in the diagnosis of malignant lesions. Very little is known about the diagnostic importance of p16 in primary prostate carcinoma and nonmalignant elements. Materials and Methods: We recruited 137 of routinely diagnostic prostatic specimens (between 2009 and 2013), which consisted of 21 prostatectomy, 15 transurethral prostatic resection, and 101 needle biopsy. We evaluated p16, in comparison with p504s, in prostatic carcinoma and benign glands. In this study, both nuclear and cytoplasmatic p16 expression were considered positive. Results: We observed p16 expression in 86% of PC specimens and 16% of benign elements ( P =0.001). Interestingly, p16 alone retained a high diagnostic potential in prostatectomy (95%) and in needle biopsy (84%), exhibiting a close association with PC. p504s had a high sensitivity (97%) and predictive negative value (98%) but a low specificity (71%) and predictive positive value (63%). In contrast, p16-positive expression showed a higher specificity (84%) and predictive positive value (74%) than p504s. Two prostatic carcinoma negative for p504s were positive for p16, whereas 7 cases negative for p16 were positive for p504s, and notably none was negative for both markers. In prostatectomy, p16 showed a higher diagnostic accuracy but not on transurethral prostatic resection. In needle biopsies, both markers were complementary, indicating that their combined detection may help in performing an accurate diagnosis. In conclusion, our data suggest that p16 expression is significantly enhanced in prostate carcinoma as compared with nonmalignant elements. Our results provide evidence that p16 and p504s together could improve the diagnosis of PC in prostatectomy and needle biopsies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Immunohistochemistry & Molecular Morphology Wolters Kluwer Health

p16 Expression in Prostate Cancer and Nonmalignant Lesions: Novel Findings and Review of the Literature

p16 Expression in Prostate Cancer and Nonmalignant Lesions: Novel Findings and Review of the Literature


The widespread use of serum prostate-specific antigen (PSA) screening has contributed to increase prostatic cancer (PC); in turn, there has been a growth in the number of specimens to be analyzed for correct diagnosis. 1–3 Sometimes the diagnosis of PC can be difficult and inaccurate owing to several reasons such as: limitation of neoplastic foci, difficulty in application of histologic criteria for adenocarcinoma, and pathologist’s inexperience. Immunohistochemistry (IHC) is a useful tool in clinical practice for diagnosis of prostatic glands. Negative immunostaining for markers such as high molecular cytokeratin and p63 are widely used as an adjunctive tool to identify the absence of a basal cell layer in the suspicious acini. However, IHC has been shown to have some limitations. 3 Basal cells can have a patchy or discontinuous distribution in some benign lesions (ie, adenosis and some atrophic glands). Consequently, the negative staining for high molecular cytokeratin and p63 in few suspicious glands cannot be a proof of their malignancy. 4 Until now, p504s (also known as α-methylayl CoA racemase or AMACR) is the only PC-specific marker used as an adjuvant tool in the diagnosis of PC. 3,5 Other cancer-specific biomarkers are expressed in prostatic carcinoma, but none of them have been used by pathologists as they lack sensitivity or specificity. 1 The p16 INK4a gene belongs to a group of proteins known as cyclin-dependent kinase inhibitors; it plays an important role in inhibiting cell-cycle progression by competitive binding to the cellular cyclins. It is a proven tumor suppressor gene, frequently inactivated in a variety of human cancers and highly expressed in the senescent cells. 6,7 Inactivation of p16 attenuates senescence and aging, playing a critical role in carcinogenesis. Cellular senescence seems to be less frequent in prostate carcinogenesis, 8 suggesting at least, in part, alternative molecular mechanisms. In rare cases where...
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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Subject
Research Articles
ISSN
1541-2016
eISSN
1533-4058
DOI
10.1097/PAI.0000000000000171
pmid
25906117
Publisher site
See Article on Publisher Site

Abstract

Background: Prostatic specimens occasionally may contain proliferative foci of the small atypical acini that display some but not all features of prostate carcinoma. p504s is the only prostatic cancer (PC)-specific marker that, in combination with basal cell markers, help in the diagnosis of malignant lesions. Very little is known about the diagnostic importance of p16 in primary prostate carcinoma and nonmalignant elements. Materials and Methods: We recruited 137 of routinely diagnostic prostatic specimens (between 2009 and 2013), which consisted of 21 prostatectomy, 15 transurethral prostatic resection, and 101 needle biopsy. We evaluated p16, in comparison with p504s, in prostatic carcinoma and benign glands. In this study, both nuclear and cytoplasmatic p16 expression were considered positive. Results: We observed p16 expression in 86% of PC specimens and 16% of benign elements ( P =0.001). Interestingly, p16 alone retained a high diagnostic potential in prostatectomy (95%) and in needle biopsy (84%), exhibiting a close association with PC. p504s had a high sensitivity (97%) and predictive negative value (98%) but a low specificity (71%) and predictive positive value (63%). In contrast, p16-positive expression showed a higher specificity (84%) and predictive positive value (74%) than p504s. Two prostatic carcinoma negative for p504s were positive for p16, whereas 7 cases negative for p16 were positive for p504s, and notably none was negative for both markers. In prostatectomy, p16 showed a higher diagnostic accuracy but not on transurethral prostatic resection. In needle biopsies, both markers were complementary, indicating that their combined detection may help in performing an accurate diagnosis. In conclusion, our data suggest that p16 expression is significantly enhanced in prostate carcinoma as compared with nonmalignant elements. Our results provide evidence that p16 and p504s together could improve the diagnosis of PC in prostatectomy and needle biopsies.

Journal

Applied Immunohistochemistry & Molecular MorphologyWolters Kluwer Health

Published: Mar 1, 2016

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