Elsevier

Gynecologic Oncology

Volume 99, Issue 1, October 2005, Pages 36-42
Gynecologic Oncology

The expression of Ki-67, p53, estrogen and progesterone receptors affecting survival in uterine leiomyosarcomas. A clinicopathologic study

https://doi.org/10.1016/j.ygyno.2005.05.019Get rights and content

Abstract

Objectives.

To evaluate the level of expression of estrogen receptor (ER), progesterone receptor (PR), p53 and Ki-67 in patients with leiomyosarcoma and to investigate the effect of these and to identify the clinical parameters on prognosis.

Materials and methods.

Twenty-four patients operated for LMS of uterine origin between 1994 and 2003 at Istanbul Medical School, Department of Obstetrics and Gynecology and Division of Gynecologic Oncology constituted our study group. The data of all patients were updated via mail or phone. The effects of stage, grade, chemotherapy, radiotherapy, number of mitoses, presence of necrosis, Ki-67 and p53 expression, presence of estrogen and progesterone receptors on survival were evaluated.

Results.

The mean follow-up period of patients is 30.42 ± 25.15 months. The mean overall survival for all LMS patients was estimated to be 48.4 ± 10.38 months. The cumulative survival ratio in the 33rd month was 33.08. Age, menopausal status, history of prior radiotherapy, number of mitoses had no statistically significant effect on overall survival in our study although stage had a significant effect. Finding of greater than 10% steroid receptor expression has a positive effect on survival ([ER P = 0.019; log rank = 5.49] and [PR P = 0.023; log rank = 5.14]). The median value of Ki-67 was calculated to be 30. There was a survival advantage in patients with Ki-67 expression (P = 0.034; log rank = 4.49) below the median value. p53 levels had no significant effect on survival (P = 0.336; log rank = 0.92).

Conclusion.

Surgical staging is an important prognostic factor in LMS patients, while number of mitoses and grade of the tumor also seem to affect prognosis. Contrary to the current literature, our findings suggest that estrogen and progesterone receptor positivity greater than 10% may be associated with a better prognosis.

Introduction

Leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS) are rare malignant smooth muscle tumors of the uterus [1], [2]. In spite of their rarity, they are hard to manage clinically due to their unpredictable recurrence rate and metastasizing capacity. Many clinicopathologic parameters affecting prognosis are investigated and among them most have controversial significance [3].

Tumor stage, histological grade, tumor size, menopausal status, age, mitotic index, tumor necrosis, and DNA ploidy are traditional prognostic factors which are previously studied. During the last decade, a number of researches have been done to assess estrogen receptors (ER), progesterone receptors (PR), and p53 and Ki-67 expression as prognostic factors in LMS [3], [4], [5].

Factors affecting transformation of uterine smooth muscle cells to LMS is not known, though ovarian steroids may have effect on this process. Many research papers have investigated the progesterone and estrogen receptor status in LMS: Zhai et al. [6] have found ER and PR expression in 57% of LMS cases; Bodner et al. [4] have found 57% and 43% positivity for ER and PR, respectively. The authors have concluded that both of the parameters do not have any effect on overall and disease-free survival.

p53 which is a nuclear phosphoprotein, is involved in the control of cellular apoptotic pathway and loss of p53 function has been implicated in the pathogenesis of many human tumors [2]. Over-expression and mutation of the tumor suppressor p53 in LMS have been reported recently. Blom have proposed that p53 over-expression has a prognostic significance in terms of disease-free survival [2].

The cell proliferation associated antigen Ki-67 is found in all phases of the cell cycle except for phase-Go, so that the tumor growth fraction in some form may be quantified by measuring it. Although this parameter has been investigated previously, the only study investigating its association with prognosis in LMS has recently been published [5]. This study concluded that increased expression of Ki-67 have been associated with worse prognosis.

The aim of our study is to evaluate the level of expression of ER, PR, p53 and Ki-67 in patients with LMS and to investigate the effect of these parameters on prognosis.

Section snippets

Subjects

Twenty-four patients operated for LMS of uterine origin between 1994 and 2003 at Istanbul Medical School, Department of Obstetrics and Gynecology and Division of Gynecologic Oncology constituted our study group. The patients were analyzed retrospectively. The surgical and medical data were retrieved from the archives of Division of Gynecologic Oncology, while macro- and microscopic data were gathered from the Department of Pathology of Istanbul Medical School.

Date of diagnosis, age, menopausal

Results

Retrospective analysis of data of Istanbul University, Istanbul Medical School, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology between 1992 and 2002 revealed 1465 patients with the diagnosis of malignant genital tumor. Out of these, 28.3% (415/1465) were diagnosed to have malignant uterine tumor. Fifty-three of these cases were uterine sarcomas. Uterine sarcomas comprised 3.6% and 12.7% of all malignant genital and uterine tumors, respectively.

Out of these 53 cases,

Discussion

Uterine sarcomas are rare, aggressive tumors with high metastatic capacity and recurrence rates even if diagnosed early. The unknown factors affecting to uterine sarcomas and the adjuvant therapies, which do not affect survival are the two main problems while dealing with uterine sarcomas [1]. Surgical staging and tumor grade are the only parameters agreed upon to affect the prognosis [1], [2]. Likewise, surgical staging is an important prognostic factor in our study, while number of mitoses

Acknowledgment

We would like to thank Prof. Dr. Rian Dişçi for the statistical help. The Research Found of The University of İstanbul supported this study, project number: T1136/18062001.

References (13)

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