Faculty Collaboration Database

PTEN loss and p27 loss differ among morphologic patterns of prostate cancer, including cribriform. Hum Pathol 2017 Jul;65:85-91

Date

05/16/2017

Pubmed ID

28504208

DOI

10.1016/j.humpath.2017.04.024

Scopus ID

2-s2.0-85021433623 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

The presence and extent of cribriform pattern of prostate cancer portend recurrence and cancer death. The relative expressions within this morphology of the prognostically adverse loss of PTEN, and the downstream inactivation of cell cycle inhibitor p27/Kip1 had been uncertain. In this study, we examined 52 cases of cribriform cancer by immunohistochemistry for PTEN, p27, and CD44 variant (v)7/8, and a subset of 17 cases by chromogenic in situ hybridization (ISH) using probes for PTEN or CDKN1B (gene for p27). The fractions of epithelial pixels positive by immunohistochemistry and ISH were digitally assessed for benign acini, high-grade prostatic intraepithelial neoplasia, and 8 morphologic patterns of cancer. Immunostaining results demonstrated that (1) PTEN loss was significant for fused small acini, cribriform-central cells, small cribriform acini, and Gleason grade 5 cells in comparison with other acini; (2) p27 loss was significant only for cribriform-peripheral cells and borderline significant for fused small acini in comparison with benign acini; and (3) CD44v7/8 showed expression loss in cribriform-peripheral cells; other comparisons were not significant. ISH showed that cribriform cancer had significant PTEN loss normalized to benign acini (P<.02), whereas Gleason 3 cancer or fused small acini did not. With CDKN1B, the degree of signal loss among various cancer morphologies was insignificant. In conclusion, molecular disparities emerged between the fused small acini and cribriform patterns of Gleason 4 cancer. PTEN or p27 loss as prognostic factors demands distinct assessment in the varieties of Gleason 4 cancer, and in the biphenotypic peripheral versus central populations in cribriform structures.

Author List

Ronen S, Abbott DW, Kravtsov O, Abdelkader A, Xu Y, Banerjee A, Iczkowski KA

Authors

Daniel W. Abbott MD Assistant Professor in the Pathology department at Medical College of Wisconsin
Anjishnu Banerjee PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Biomarkers, Tumor
Biopsy
Cyclin-Dependent Kinase Inhibitor p27
Down-Regulation
Humans
Immunohistochemistry
In Situ Hybridization
Male
Middle Aged
Neoplasm Grading
PTEN Phosphohydrolase
Predictive Value of Tests
Prostatectomy
Prostatic Neoplasms