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Diagnostic Pathology
Published in: Diagnostic Pathology 1/2016

Open Access 01-12-2016 | Research

In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity

Authors: Emese Irma Ágoston, Tamás Micsik, Balázs Ács, Krisztina Fekete, Oszkár Hahn, Zsolt Baranyai, Kristóf Dede, György Bodoky, Attila Bursics, Janina Kulka, Tibor Krenács, Balázs Győrffy, László Harsányi, A. Marcell Szász

Published in: Diagnostic Pathology | Issue 1/2016

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Abstract

Background

Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) loss of function is frequently detected in advanced colorectal cancer. Its detection is thought to have prognostic significance and it is being considered to predict responsiveness to anti-EGFR therapy. Unfortunately, while immunohistochemical assessment of PTEN expression is widespread, it lacks standardization and the results are hardly comparable across the available publications.

Methods

Retrospectively collected, formalin-fixed and paraffin-embedded colorectal tumor tissue samples from 55 patients were combined into tissue microarray (TMA) blocks. We used three different PTEN antibodies to determine the frequency, intensity and intracellular pattern of PTEN immunohistochemical labeling: Neomarkers, Dako and CellSignaling. We evaluated the aforementioned parameters in selected regions of colorectal cancers and in their lymph node metastases by using three scoring methods that take into consideration both staining frequency and intensity (H1-H3-score). We also evaluated intracellular localization.

Results

The Dako and CellSignaling antibodies stained predominantly cytoplasms, while the Neomarkers antibody specifically stained cell nuclei. PTEN H-scores were significantly lower in all tumor areas as compared to the normal colonic mucosa based on staining with the DAKO and CellSignaling antibodies. Intratumoral regional differences or differences between matching tumors and metastases were not detected with any of the antibodies. Neither Dako, neither CellSignaling, nor the Neomarkers antibodies revealed a significant correlation between PTEN expression and pT, Dukes/MAC and clinical stage. KRAS status, histological grade correlated with PTEN H-scores based on staining with the Neomarkers antibody. PTEN H-scores did not correlate with MMR status. PTEN H-scores did not show any correlation with relapse-free survival based on staining with either antibody.

Conclusions

While PTEN expression decreased in colorectal cancer according to two antibodies, neither of the three applied PTEN antibodies could justify significant correlation with clinicopathological data, nor had prognostic value. Thus, we might conclude that immunohistochemical PTEN investigation remains a challenge requiring more standardized evaluation on larger number of cases to clarify its utility as a prognostic and predictive tool in CRC. The standardization of immunohistochemical method is key in the evaluation process, which is further discussed.
Appendix
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Metadata
Title
In depth evaluation of the prognostic and predictive utility of PTEN immunohistochemistry in colorectal carcinomas: performance of three antibodies with emphasis on intracellular and intratumoral heterogeneity
Authors
Emese Irma Ágoston
Tamás Micsik
Balázs Ács
Krisztina Fekete
Oszkár Hahn
Zsolt Baranyai
Kristóf Dede
György Bodoky
Attila Bursics
Janina Kulka
Tibor Krenács
Balázs Győrffy
László Harsányi
A. Marcell Szász
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2016
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-016-0508-0

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