Immunohistochemical markers of cell cycle control applied to ovarian and primary peritoneal surface epithelial neoplasms: p21(WAF1/CIP1) predicts survival and good response to platinin-based chemotherapy

Michael J. Costa, Christian L. Hansen, Judy E. Walls, Sidney A Scudder

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Abstract

Immunohistochemistry for p53, p21(WAF1)/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti- p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki- 67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50%+ and p21(WAF1/CIP1) 65%+. Ki-67PI ranged from 4% to 88% (mean/median = 44/46%). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10-7, .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10-8, 1 x 10-5). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10-5/1 x 10-6, .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10- 6, 1 x 10-10 1 x 10-10/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10-6). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical predictors, p53 IMS, and Ki-67PI in this series of 117 PTs with SENs. Our preliminary data suggest an interrelationship between p21(WAF1/CIP1) expression and an effective clinical response to platinin-based chemotherapy, both associated with apoptosis. Further investigation seems warranted.

Original languageEnglish (US)
Pages (from-to)640-647
Number of pages8
JournalHuman Pathology
Volume30
Issue number6
DOIs
StatePublished - Jun 1999

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Glandular and Epithelial Neoplasms
Cell Cycle Checkpoints
Drug Therapy
Histology
Cell Cycle
Clone Cells
Staining and Labeling
Cyclin-Dependent Kinases
Oncogenes
Paraffin
Immunohistochemistry
Apoptosis
Survival

Keywords

  • Adenocarcinoma
  • Cancer
  • Carcinoma
  • Clear cell
  • Endometrioid
  • Immunohistochemistry
  • Ki- 67
  • Ovary
  • p53
  • Serous
  • Transitional cell mucinous

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{686d26b8c700461eb93e710702b2b9ed,
title = "Immunohistochemical markers of cell cycle control applied to ovarian and primary peritoneal surface epithelial neoplasms: p21(WAF1/CIP1) predicts survival and good response to platinin-based chemotherapy",
abstract = "Immunohistochemistry for p53, p21(WAF1)/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti- p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki- 67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50{\%}+ and p21(WAF1/CIP1) 65{\%}+. Ki-67PI ranged from 4{\%} to 88{\%} (mean/median = 44/46{\%}). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10-7, .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10-8, 1 x 10-5). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10-5/1 x 10-6, .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10- 6, 1 x 10-10 1 x 10-10/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10-6). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical predictors, p53 IMS, and Ki-67PI in this series of 117 PTs with SENs. Our preliminary data suggest an interrelationship between p21(WAF1/CIP1) expression and an effective clinical response to platinin-based chemotherapy, both associated with apoptosis. Further investigation seems warranted.",
keywords = "Adenocarcinoma, Cancer, Carcinoma, Clear cell, Endometrioid, Immunohistochemistry, Ki- 67, Ovary, p53, Serous, Transitional cell mucinous",
author = "Costa, {Michael J.} and Hansen, {Christian L.} and Walls, {Judy E.} and Scudder, {Sidney A}",
year = "1999",
month = "6",
doi = "10.1016/S0046-8177(99)90088-6",
language = "English (US)",
volume = "30",
pages = "640--647",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Immunohistochemical markers of cell cycle control applied to ovarian and primary peritoneal surface epithelial neoplasms

T2 - p21(WAF1/CIP1) predicts survival and good response to platinin-based chemotherapy

AU - Costa, Michael J.

AU - Hansen, Christian L.

AU - Walls, Judy E.

AU - Scudder, Sidney A

PY - 1999/6

Y1 - 1999/6

N2 - Immunohistochemistry for p53, p21(WAF1)/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti- p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki- 67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50%+ and p21(WAF1/CIP1) 65%+. Ki-67PI ranged from 4% to 88% (mean/median = 44/46%). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10-7, .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10-8, 1 x 10-5). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10-5/1 x 10-6, .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10- 6, 1 x 10-10 1 x 10-10/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10-6). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical predictors, p53 IMS, and Ki-67PI in this series of 117 PTs with SENs. Our preliminary data suggest an interrelationship between p21(WAF1/CIP1) expression and an effective clinical response to platinin-based chemotherapy, both associated with apoptosis. Further investigation seems warranted.

AB - Immunohistochemistry for p53, p21(WAF1)/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti- p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki- 67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50%+ and p21(WAF1/CIP1) 65%+. Ki-67PI ranged from 4% to 88% (mean/median = 44/46%). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10-7, .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10-8, 1 x 10-5). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10-5/1 x 10-6, .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10- 6, 1 x 10-10 1 x 10-10/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10-6). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical predictors, p53 IMS, and Ki-67PI in this series of 117 PTs with SENs. Our preliminary data suggest an interrelationship between p21(WAF1/CIP1) expression and an effective clinical response to platinin-based chemotherapy, both associated with apoptosis. Further investigation seems warranted.

KW - Adenocarcinoma

KW - Cancer

KW - Carcinoma

KW - Clear cell

KW - Endometrioid

KW - Immunohistochemistry

KW - Ki- 67

KW - Ovary

KW - p53

KW - Serous

KW - Transitional cell mucinous

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U2 - 10.1016/S0046-8177(99)90088-6

DO - 10.1016/S0046-8177(99)90088-6

M3 - Article

C2 - 10374771

AN - SCOPUS:0033066168

VL - 30

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EP - 647

JO - Human Pathology

JF - Human Pathology

SN - 0046-8177

IS - 6

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