Clinical Investigation: Cervix
Progesterone receptor is a favorable prognostic factor of radiation therapy for adenocarcinoma of the uterine cervix

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Abstract

Purpose: The prognostic significance of the expression of estrogen receptors (ER) and progesterone receptors (PgR) in adenocarcinoma of the uterine cervix has been controversial. Hence, the relationship between the expression of the hormone receptors and clinical outcome was evaluated for patients with adenocarcinoma treated with radiation therapy alone.

Materials and Methods: This study involved 66 patients with cervical adenocarcinoma consisting of 44 adenocarcinomas and 22 adeno-squamous cell carcinomas. They received radiation therapy at the National Institute of Radiological Sciences Hospital between 1962 and 1993. The mean age of the patients was 62.0 ± 12.0 years (range, 36–82 years). The numbers of patients with Stage I, II, III, and IV diseases were 7, 17, 27, and 15, respectively. Their ER and PgR statuses were investigated immunohistochemically using biopsy specimens excised from the cervical tumors before radiation therapy.

Results: ER staining was positive in 12 patients (19%). ER status did not correlate with the 5-year cause-specific, local-control, and disease-free survivals. PgR staining was positive in 12 patients (19%). The disease-free survival rate of PgR-positive patients was significantly higher than that of PgR-negative patients (p = 0.044). Although PgR status did not reach statistical significance in relation to the 5-year cause-specific survival and local-control survival, the better survival was due to less local recurrence rather than to less distant metastasis.

Conclusion: The present study suggested that PgR status was associated with prognosis after radiation therapy for adenocarcinoma of the uterine cervix.

Introduction

Advanced squamous cell carcinoma of the uterine cervix has relatively better prognosis, and radiation therapy is one of the effective treatment modalities because of the relatively high sensitivity to radiation and the advantage of high-dose irradiation with brachytherapy. In contrast, adenocarcinoma of the uterine cervix has relatively poorer prognosis compared with squamous cell carcinoma due to a lower sensitivity to radiation 1, 2 or a higher incidence of distant metastasis (3). There are only a few reports that analyzed the prognostic significance of various clinical parameters and types of treatment methods in adenocarcinoma of the cervix using a large number of patients. Hence, there are no standard treatment methods for adenocarcinoma of the uterine cervix that are generally accepted worldwide. In recent years, as the incidence of adenocarcinoma of the uterine cervix has been gradually increasing in comparison with the previous decade 3, 4, 5, 6, this particular cancer treated with radiation therapy alone is a subject requiring urgent evaluation.

Estrogen receptors (ER) and progesterone receptors (PgR) are observed in breast, ovary, etc. The normal uterine cervix also possesses both ER and PgR 7, 8. Moreover, ER and PgR are often observed in malignant tumors in hormone-dependent organs, such as breast cancer, uterine corpus cancer, and ovarian cancer. In regard to adenocarcinoma of the uterine cervix, ER and PgR positivities were reported to exist in 20–35% of the patients 9, 10. Expression of ER or PgR was reported to be a preferable prognostic factor in breast cancer (11), uterine corpus cancer (12), and ovarian cancer 13, 14, and, therefore, to represent a marker for a possibly favorable response to hormonal therapy 15, 16. However, the prognostic significance of the expression of ER and PgR in adenocarcinoma of the uterine cervix has scarcely been reported.

In this study, we investigated the relationship between the expression of the hormone receptors and the outcome of patients treated with radiation therapy alone with long-term follow-up.

Section snippets

Patients and specimens

This study involved 66 patients with adenocarcinoma or adeno-squamous cell carcinoma of the uterine cervix who received radiation therapy at the National Institute of Radiological Sciences Hospital in Chiba, Japan, between 1962 and 1993. We investigated all the adenocarcinomas treated with radiation therapy alone for which we could obtain their paraffin-embedded tumor samples.

The mean age of the patients was 62.0 ± 12.0 years (range, 36–82 years). Their clinical stage and histologic

Results

Both ER and PgR were present in the nuclei of cancer cells Fig. 1, Fig. 2. ER staining was positive in 12 patients, a positive rate of 19%. PgR staining was also positive in 12 patients (19%).

The correlation between hormone receptor expression and clinical characteristics is shown in Table 2. ER-positive carcinomas showed the highest correlation in Stage IV, followed by Stage II, Stage I, and Stage III. PgR positivities were the highest in Stage II, followed by Stage III, Stage I, and Stage

Discussion

Correlation between ER or PgR status and prognosis has been reported in early-stage adenocarcinoma of the cervix treated with surgery. Masood et al. reported that 14 of 51 patients (27%) with Stage I and II disease were ER positive and 17 of 51 (33%) PgR positive by immunohistochemical staining method (9). Fujiwara et al. reported that 17 of 84 patients (20%) with Stage I and II disease were ER positive and 23 of 84 patients (27%) PgR positive (10). However, to our knowledge, this is the first

Acknowledgements

The authors thank Prof. Niibe of the Department of Radiology and Radiation Oncology, Gunma University School of Medicine, for his helpful suggestions and significant scientific support.

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