Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma

M. Bradley Silverman, Patrick C. Roche, Rosanne M. Kho, Gary Keeney, Hongzhe Li, Karl C. Podratz

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective. Our objective was to determine whether cytokinetic and molecular analyses of curettage specimens can provide a mechanism for triage of patients with endometrial cancer before initiating definitive surgical treatment. Methods. Pretreatment analysis consisted of flow cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohistochemical determination of expression of proliferating cell nuclear antigen, HER-2/neu, and p53 in curettage specimens from 134 patients with endometrial carcinoma who subsequently had surgical staging and definitive surgical treatment. Fisher's exact test or χ2 was used to examine the association between pretreatment variables and traditional surgical-pathologic indices. The log-rank test was used for univariate survival analysis. Cox proportional hazards identified the most important molecular factors. Results. Nondiploid status, SPF ≥9%, and PI ≥14% were associated with the traditional posttreatment prognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF ≥9%, PI ≥14%, and p53 overexpression and decreased progression-free survival (PITS) and disease- related survival (DRS). Stepwise Cox regression analysis identified p53 overexpression and SPF ≥9% as the most significant pretreatment molecular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that when both factors are present the risk for recurrence was higher (RR = 7.07; 95% confidence interval [CI], 3.06-16.38; P < 0.01) and death due to disease was higher (RR = 9.93; 95% CI, 3.92-25.19; P < 0.01) than when no factors are present. In the group with both factors, 5-year PFS and DRS estimates were 41 and 44%, respectively, compared with 86 and 86% and 90 and 92% for the 'none' and 'one' groups, respectively. Conclusion. When observed simultaneously, increased SPF and p53 overexpression defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens could provide a mechanism of triage that could be applied before definitive surgical treatment. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalGynecologic Oncology
Volume77
Issue number1
DOIs
StatePublished - Apr 2000

Fingerprint

Endometrial Neoplasms
S Phase
Curettage
Triage
Survival Analysis
Confidence Intervals
Recurrence
Survival
Ploidies
Proliferating Cell Nuclear Antigen
Disease-Free Survival
Therapeutics
Regression Analysis

Keywords

  • Cytokinetics
  • Endometrial carcinoma
  • HER- 2/neu
  • p53
  • PCNA
  • Progression
  • Risk assessment

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Obstetrics and Gynecology

Cite this

Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma. / Silverman, M. Bradley; Roche, Patrick C.; Kho, Rosanne M.; Keeney, Gary; Li, Hongzhe; Podratz, Karl C.

In: Gynecologic Oncology, Vol. 77, No. 1, 04.2000, p. 1-7.

Research output: Contribution to journalArticle

Silverman, M. Bradley ; Roche, Patrick C. ; Kho, Rosanne M. ; Keeney, Gary ; Li, Hongzhe ; Podratz, Karl C. / Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma. In: Gynecologic Oncology. 2000 ; Vol. 77, No. 1. pp. 1-7.
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AU - Roche, Patrick C.

AU - Kho, Rosanne M.

AU - Keeney, Gary

AU - Li, Hongzhe

AU - Podratz, Karl C.

PY - 2000/4

Y1 - 2000/4

N2 - Objective. Our objective was to determine whether cytokinetic and molecular analyses of curettage specimens can provide a mechanism for triage of patients with endometrial cancer before initiating definitive surgical treatment. Methods. Pretreatment analysis consisted of flow cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohistochemical determination of expression of proliferating cell nuclear antigen, HER-2/neu, and p53 in curettage specimens from 134 patients with endometrial carcinoma who subsequently had surgical staging and definitive surgical treatment. Fisher's exact test or χ2 was used to examine the association between pretreatment variables and traditional surgical-pathologic indices. The log-rank test was used for univariate survival analysis. Cox proportional hazards identified the most important molecular factors. Results. Nondiploid status, SPF ≥9%, and PI ≥14% were associated with the traditional posttreatment prognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF ≥9%, PI ≥14%, and p53 overexpression and decreased progression-free survival (PITS) and disease- related survival (DRS). Stepwise Cox regression analysis identified p53 overexpression and SPF ≥9% as the most significant pretreatment molecular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that when both factors are present the risk for recurrence was higher (RR = 7.07; 95% confidence interval [CI], 3.06-16.38; P < 0.01) and death due to disease was higher (RR = 9.93; 95% CI, 3.92-25.19; P < 0.01) than when no factors are present. In the group with both factors, 5-year PFS and DRS estimates were 41 and 44%, respectively, compared with 86 and 86% and 90 and 92% for the 'none' and 'one' groups, respectively. Conclusion. When observed simultaneously, increased SPF and p53 overexpression defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens could provide a mechanism of triage that could be applied before definitive surgical treatment. (C) 2000 Academic Press.

AB - Objective. Our objective was to determine whether cytokinetic and molecular analyses of curettage specimens can provide a mechanism for triage of patients with endometrial cancer before initiating definitive surgical treatment. Methods. Pretreatment analysis consisted of flow cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohistochemical determination of expression of proliferating cell nuclear antigen, HER-2/neu, and p53 in curettage specimens from 134 patients with endometrial carcinoma who subsequently had surgical staging and definitive surgical treatment. Fisher's exact test or χ2 was used to examine the association between pretreatment variables and traditional surgical-pathologic indices. The log-rank test was used for univariate survival analysis. Cox proportional hazards identified the most important molecular factors. Results. Nondiploid status, SPF ≥9%, and PI ≥14% were associated with the traditional posttreatment prognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF ≥9%, PI ≥14%, and p53 overexpression and decreased progression-free survival (PITS) and disease- related survival (DRS). Stepwise Cox regression analysis identified p53 overexpression and SPF ≥9% as the most significant pretreatment molecular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that when both factors are present the risk for recurrence was higher (RR = 7.07; 95% confidence interval [CI], 3.06-16.38; P < 0.01) and death due to disease was higher (RR = 9.93; 95% CI, 3.92-25.19; P < 0.01) than when no factors are present. In the group with both factors, 5-year PFS and DRS estimates were 41 and 44%, respectively, compared with 86 and 86% and 90 and 92% for the 'none' and 'one' groups, respectively. Conclusion. When observed simultaneously, increased SPF and p53 overexpression defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens could provide a mechanism of triage that could be applied before definitive surgical treatment. (C) 2000 Academic Press.

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KW - Endometrial carcinoma

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KW - p53

KW - PCNA

KW - Progression

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