International Journal of Radiation Oncology*Biology*Physics
Clinical Investigation: CervixProgesterone receptor is a favorable prognostic factor of 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.
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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.
References (24)
- et al.
Prognosis of the adenocarcinoma of the cervix uteriA comparative study
Gynecol Oncol
(1989) - et al.
Prognostic factors of primary adenocarcinoma of the uterine cervix
Gynecol Oncol
(1998) - et al.
Specific estrogen binding proteins in human cervix
J Steroid Biochem
(1975) - et al.
Hormone action in human cervixII. Specific progesterone binding proteins in human cervix
J Steroid Biochem
(1976) - et al.
Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma
Gynecol Oncol
(1998) - et al.
Steroid receptors in ovarian carcinomaImmunohistochemical determination may lead to new aspects
Gynecol Oncol
(1992) - et al.
Estrogen and progestin receptor levels as prognostic factors for survival in endometrial cancer
Gynecol Oncol
(1988) - et al.
Radiation therapy alone for adenocarcinoma of the uterine cervix
Int J Radiat Oncol Biol Phys
(1995) - et al.
Steroid hormone receptors in carcinoma of the cervixLack of response to an antiestrogen
Gynecol Oncol
(1990) - et al.
Controversies in the management of cervical adenocarcinoma
Obstet Gynecol
(1988)
Adenocarcinoma of the uterine cervixPrognosis and patterns of failure in 367 cases
Cancer
Squamous and adenocarcinoma of the uterine cervixA comparison using routine data
Br J Cancer
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