Molecular and histopathologic predictors of distant failure in endometrial cancer

Andrea Mariani, Thomas J. Sebo, Maurice J. Webb, Darren Riehle, Jerry A. Katzmann, Gary Keeney, Patrick C. Roche, Timothy G. Lesnick, Karl C. Podratz

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction ≥9%, proliferative index ≥14%, and DNA index ≥1.5 significantly (P < 0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR = 43.73; P < 0.005), lymphovascular invasion (OR = 11.59; P < 0.001), and cervical stromal invasion (OR = 11.29; P = 0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P < 0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.

Original languageEnglish (US)
Pages (from-to)434-441
Number of pages8
JournalCancer Detection and Prevention
Volume27
Issue number6
DOIs
StatePublished - 2003

Fingerprint

Endometrial Neoplasms
Recurrence
Logistic Models
Ploidies
DNA
Proliferating Cell Nuclear Antigen
Aneuploidy
Vagina
Hysterectomy
Pelvis
S Phase
Cell Biology
Histology
Flow Cytometry
Cohort Studies
Lymph Nodes
Cell Proliferation
Cell Membrane
Staining and Labeling
Population

Keywords

  • Cytokinetics
  • Endometrial cancer-study
  • Neoplasm
  • Prognosis
  • Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mariani, A., Sebo, T. J., Webb, M. J., Riehle, D., Katzmann, J. A., Keeney, G., ... Podratz, K. C. (2003). Molecular and histopathologic predictors of distant failure in endometrial cancer. Cancer Detection and Prevention, 27(6), 434-441. https://doi.org/10.1016/j.cdp.2003.09.005

Molecular and histopathologic predictors of distant failure in endometrial cancer. / Mariani, Andrea; Sebo, Thomas J.; Webb, Maurice J.; Riehle, Darren; Katzmann, Jerry A.; Keeney, Gary; Roche, Patrick C.; Lesnick, Timothy G.; Podratz, Karl C.

In: Cancer Detection and Prevention, Vol. 27, No. 6, 2003, p. 434-441.

Research output: Contribution to journalArticle

Mariani, A, Sebo, TJ, Webb, MJ, Riehle, D, Katzmann, JA, Keeney, G, Roche, PC, Lesnick, TG & Podratz, KC 2003, 'Molecular and histopathologic predictors of distant failure in endometrial cancer', Cancer Detection and Prevention, vol. 27, no. 6, pp. 434-441. https://doi.org/10.1016/j.cdp.2003.09.005
Mariani, Andrea ; Sebo, Thomas J. ; Webb, Maurice J. ; Riehle, Darren ; Katzmann, Jerry A. ; Keeney, Gary ; Roche, Patrick C. ; Lesnick, Timothy G. ; Podratz, Karl C. / Molecular and histopathologic predictors of distant failure in endometrial cancer. In: Cancer Detection and Prevention. 2003 ; Vol. 27, No. 6. pp. 434-441.
@article{40b0b84cd182429290d9d1a1c79a5faf,
title = "Molecular and histopathologic predictors of distant failure in endometrial cancer",
abstract = "A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13{\%} of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50{\%}, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33{\%}, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction ≥9{\%}, proliferative index ≥14{\%}, and DNA index ≥1.5 significantly (P < 0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR = 43.73; P < 0.005), lymphovascular invasion (OR = 11.59; P < 0.001), and cervical stromal invasion (OR = 11.29; P = 0.001) as cogent predictors of distant failures. Only 3{\%} of patients without any of these three predictors developed distant failures compared with 36{\%} of those with at least one of the three (P < 0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.",
keywords = "Cytokinetics, Endometrial cancer-study, Neoplasm, Prognosis, Recurrence",
author = "Andrea Mariani and Sebo, {Thomas J.} and Webb, {Maurice J.} and Darren Riehle and Katzmann, {Jerry A.} and Gary Keeney and Roche, {Patrick C.} and Lesnick, {Timothy G.} and Podratz, {Karl C.}",
year = "2003",
doi = "10.1016/j.cdp.2003.09.005",
language = "English (US)",
volume = "27",
pages = "434--441",
journal = "Cancer Epidemiology",
issn = "1877-7821",
publisher = "Elsevier BV",
number = "6",

}

TY - JOUR

T1 - Molecular and histopathologic predictors of distant failure in endometrial cancer

AU - Mariani, Andrea

AU - Sebo, Thomas J.

AU - Webb, Maurice J.

AU - Riehle, Darren

AU - Katzmann, Jerry A.

AU - Keeney, Gary

AU - Roche, Patrick C.

AU - Lesnick, Timothy G.

AU - Podratz, Karl C.

PY - 2003

Y1 - 2003

N2 - A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction ≥9%, proliferative index ≥14%, and DNA index ≥1.5 significantly (P < 0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR = 43.73; P < 0.005), lymphovascular invasion (OR = 11.59; P < 0.001), and cervical stromal invasion (OR = 11.29; P = 0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P < 0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.

AB - A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction ≥9%, proliferative index ≥14%, and DNA index ≥1.5 significantly (P < 0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR = 43.73; P < 0.005), lymphovascular invasion (OR = 11.59; P < 0.001), and cervical stromal invasion (OR = 11.29; P = 0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P < 0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.

KW - Cytokinetics

KW - Endometrial cancer-study

KW - Neoplasm

KW - Prognosis

KW - Recurrence

UR - http://www.scopus.com/inward/record.url?scp=0344736649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344736649&partnerID=8YFLogxK

U2 - 10.1016/j.cdp.2003.09.005

DO - 10.1016/j.cdp.2003.09.005

M3 - Article

C2 - 14642551

AN - SCOPUS:0344736649

VL - 27

SP - 434

EP - 441

JO - Cancer Epidemiology

JF - Cancer Epidemiology

SN - 1877-7821

IS - 6

ER -