The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors

Alon D. Altman, Gregg S. Nelson, Prafull Ghatage, John B. McIntyre, David Capper, Pamela Chu, Jill G. Nation, Anthony Karnezis, Guangming Han, Steve E. Kalloger, Martin Köbel

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (>60%), and CDKN2A was scored as either negative/patchy (<90%) or block expression (>90%). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a negative predictive value of 98%. These markers can, therefore, be used on small biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.

Original languageEnglish (US)
Pages (from-to)1255-1263
Number of pages9
JournalModern Pathology
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Carcinoma
Neoplasms
Paracentesis
Biopsy
Ovarian Neoplasms
Clone Cells
Immunohistochemistry
Clinical Trials
Antibodies
Therapeutics

Keywords

  • CDKN2A
  • high-grade serous carcinoma
  • low-grade serous carcinoma
  • ovarian carcinoma
  • serous borderline tumor
  • TP53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Altman, A. D., Nelson, G. S., Ghatage, P., McIntyre, J. B., Capper, D., Chu, P., ... Köbel, M. (2013). The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors. Modern Pathology, 26(9), 1255-1263. https://doi.org/10.1038/modpathol.2013.55

The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors. / Altman, Alon D.; Nelson, Gregg S.; Ghatage, Prafull; McIntyre, John B.; Capper, David; Chu, Pamela; Nation, Jill G.; Karnezis, Anthony; Han, Guangming; Kalloger, Steve E.; Köbel, Martin.

In: Modern Pathology, Vol. 26, No. 9, 01.09.2013, p. 1255-1263.

Research output: Contribution to journalArticle

Altman, AD, Nelson, GS, Ghatage, P, McIntyre, JB, Capper, D, Chu, P, Nation, JG, Karnezis, A, Han, G, Kalloger, SE & Köbel, M 2013, 'The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors', Modern Pathology, vol. 26, no. 9, pp. 1255-1263. https://doi.org/10.1038/modpathol.2013.55
Altman, Alon D. ; Nelson, Gregg S. ; Ghatage, Prafull ; McIntyre, John B. ; Capper, David ; Chu, Pamela ; Nation, Jill G. ; Karnezis, Anthony ; Han, Guangming ; Kalloger, Steve E. ; Köbel, Martin. / The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors. In: Modern Pathology. 2013 ; Vol. 26, No. 9. pp. 1255-1263.
@article{940cf4057c824b3085bd38dabc63bf69,
title = "The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors",
abstract = "Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (>60{\%}), and CDKN2A was scored as either negative/patchy (<90{\%}) or block expression (>90{\%}). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89{\%}, a specificity of 93{\%}, a positive predictive value of 68{\%}, and a negative predictive value of 98{\%}. These markers can, therefore, be used on small biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.",
keywords = "CDKN2A, high-grade serous carcinoma, low-grade serous carcinoma, ovarian carcinoma, serous borderline tumor, TP53",
author = "Altman, {Alon D.} and Nelson, {Gregg S.} and Prafull Ghatage and McIntyre, {John B.} and David Capper and Pamela Chu and Nation, {Jill G.} and Anthony Karnezis and Guangming Han and Kalloger, {Steve E.} and Martin K{\"o}bel",
year = "2013",
month = "9",
day = "1",
doi = "10.1038/modpathol.2013.55",
language = "English (US)",
volume = "26",
pages = "1255--1263",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - The diagnostic utility of TP53 and CDKN2A to distinguish ovarian high-grade serous carcinoma from low-grade serous ovarian tumors

AU - Altman, Alon D.

AU - Nelson, Gregg S.

AU - Ghatage, Prafull

AU - McIntyre, John B.

AU - Capper, David

AU - Chu, Pamela

AU - Nation, Jill G.

AU - Karnezis, Anthony

AU - Han, Guangming

AU - Kalloger, Steve E.

AU - Köbel, Martin

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (>60%), and CDKN2A was scored as either negative/patchy (<90%) or block expression (>90%). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a negative predictive value of 98%. These markers can, therefore, be used on small biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.

AB - Low-grade serous carcinomas and serous borderline tumors, combined herein and referred to as low-grade serous tumors, show distinct molecular alterations and clinical behaviors compared with high-grade serous carcinomas. The discrimination between low-grade serous tumors and high-grade serous carcinomas can be challenging on small tissue samples, such as cell blocks of paracentesis fluid or biopsies from omental disease. The purpose of this study was to test the ability of TP53 and CDKN2A immunohistochemistry to distinguish between high-grade serous carcinomas and low-grade serous tumors on small tissue samples. Tissue microarrays containing 582 high-grade serous carcinomas, 45 low-grade serous carcinomas, and 49 serous borderline tumors, confirmed by contemporary histopathological review, were stained for TP53 and CDKN2A (DO7 and E6H4 antibody clones, respectively). TP53 was scored as completely absent, wild-type pattern or overexpressed (>60%), and CDKN2A was scored as either negative/patchy (<90%) or block expression (>90%). The combination of the two markers, ie, the TP53 wild-type pattern and CDKN2A patchy expression, had sensitivity for low-grade serous tumors of 89%, a specificity of 93%, a positive predictive value of 68%, and a negative predictive value of 98%. These markers can, therefore, be used on small biopsies/cell blocks to refute a diagnosis of low-grade serous tumors. These findings may inform emerging neoadjuvant therapeutic strategies in advanced ovarian cancers and may be crucial for future clinical trials on molecular-based therapies.

KW - CDKN2A

KW - high-grade serous carcinoma

KW - low-grade serous carcinoma

KW - ovarian carcinoma

KW - serous borderline tumor

KW - TP53

UR - http://www.scopus.com/inward/record.url?scp=84883864561&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883864561&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2013.55

DO - 10.1038/modpathol.2013.55

M3 - Article

C2 - 23558569

AN - SCOPUS:84883864561

VL - 26

SP - 1255

EP - 1263

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 9

ER -