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Steroid receptors and ovarian tumors: Variation within primary tumors and between primary tumors and metastases
GYNECOLOGIC ONCOLOGY31, 424--429 (1988)
Steroid Receptors and Ovarian Tumors: Variation within Primary Tumors and between Primary Tumors and Metastases M. A. QUINN,* R. M. ROME,-~ M. CAUCHI,'~ AND D. W. FORTUNEt .*University of Melbourne and ?Royal Women's Hospital. Melboarne, Aastralia Received April 2, 1987 Estrogen and progesterone receptors have been measured in primary and secondary ovarian carcinoma in eight patients, in bilateral ovarian tumors in 16 patients, and from multiple sites within the same tumor in 16 patients (12 primary and 4 secondary). In the majority of cases, metastatic tumors contained less receptors than their primary tumors. Marked variations in receptor content were noted within the same tumor and between bilateral tumors. This variation in receptor levels may explain the discrepancy between the presence of receptors and the response to hormonal treatment. Multiple sites of ovarian carcinoma need to be assayed for receptor content before a final decision can be made on receptor status. © 1988AcademicPress, Inc.
INTRODUCTION Approximately 65% of ovarian carcinomas contain estrogen receptors (ER) and 40% progesterone receptors yet only about 20% of patients respond to hormone therapy [1]. In breast cancer, however, the presence of ER and/or PR gives an excellent guide to response to hormonal manipulation [2]. This discrepancy between the presence of receptors and the response to endocrine therapy in patients with ovarian carcinoma may reflect the relatively low levels of receptors present or, in fact, may be due to a variation in receptor levels, either within the primary tumor or within metastatic disease, or both. We have investigated this latter possibility, by analyzing the receptor content of different sites within primary and metastatic tumors.
PATIENTS AND METHODS Tissue specimens from 39 cases of ovarian malignancy and 1 case of bilateral benign serous tumor were removed at the time of primary surgery and assay for E R and PR performed on either fresh tissue or tissue which had been previously frozen to -80°C in liquid nitrogen. Only nonnecrotic malignant tissue was taken -for analysis and adjoining specimens were used rather than specimens from different sites of the tumor. Assay methodology, using a multiple point analysis, was as described previously [3]. Histological examination was made on each tissue specimen and tumor type and grading of differentiation were ascertained. Receptor assays were performed only when samples were of uniform histological 424
0090-0258/88 $1.50 Copyright © 1988 by Academic Press. Inc. All rights of reproduction in any form reserved.
STEROID RECEPTOR VARIATION IN OVARIAN CANCER
425
TABLE 1 VARIATION IN RECEPTOR CONTENT WITHIN TUMORS
Patient No. 1 2 3 4 5 6
7 8 9 10 11 12 13 14 15 16
ER"
PR b
Histology"
0 0 23 39 207 133 211 71 49 0 6 15 8 15 0 0 0 0 334 17 7 49 37 223 149 162 96 23 21 26 0 7 10
95 96 14 9 14 12 39 9 29 0 0 20 0 12 0 6 21 0 0 13 0 66 32 27 30 18 8 0 8 45 8 0 0
Primary borderline muclnous tumor Primary borderline muclnous tumor Primary borderline mucmous tumor Primary borderline mucmous tumor Primary G, serous carcinoma Primary G~ serous carcinoma Primary Gs serous carcinoma Primary G3 serous carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G~ endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G~ endometrioid carcinoma Primary G3 adenocarcinoma Primary Gs adenocarcinoma Primary G3 adenocarcinoma Primary G3 adenocarcinoma Primary G~ adenocarcinoma Primary G3 adenocarcinoma " Primary malignant Mullerian tumor ' Primary malignant Mullerian tumor Omental deposit G~ serous carcinoma Omental deposit G~ serous carcinoma Omental deposit G3 serous carcinoma Omental deposit G3 serous carcinoma Omental deposit G 3 mucinous carcinoma Omental deposit G3 mucinous carcinoma Omental deposit G2 adenocarcinoma Omental deposit G2 adenocarcinoma
° ER, estrogen receptor (fmol/mg protein). b PR, progesterone receptor (fmol/mg protein). " G~, well-differentiated; G2, moderately well-differentiated; G3, poorly differentiated.
t y p e a n d g r a d i n g s i n c e b o t h t h e s e v a r i a b l e s m a y a f f e c t r e c e p t o r c o n t e n t [3]. A l e v e l o f 5 f m o l / m g p r o t e i n o r m o r e o f r e c e p t o r w a s t a k e n as a p o s i t i v e r e s u l t , all s a m p l e s f r o m e a c h p a t i e n t w e r e a n a l y z e d w i t h i n t h e o n e a s s a y . T h e w i t h i n a s s a y v a r i a t i o n w a s less t h a n 10% f o r all s a m p l e s .
RESULTS T ab l e 1 depicts the steroid r e c e p t o r levels and histology in 2 p r i m a r y proliferating m u c i n o u s t u m o r s , 10 p r i m a r y m a l i g n a n t t u m o r s , an d 4 m e t a s t a t i c t u m o r s w h e r e
426
QUINN ET AL. TABLE 2 STEROIDRECEPTORSIN BILATERALOVARIANTUMORS
Patient No.
ER a
PRb
Histology'
17
8 6 21 8 274 118 49 153 8 0 0 7 10 17 9 0 55 0 0 0 49 197 48 16 0 76 13 34 9 0 27 19
116 63 336 13 0 11 49 74 5 20 0 0 13 0 133 59 0 0 0 0 29 15 0 0 0 0 0 20 20 25 65 0
Benign serous Benign serous Proliferating serous Proliferating serous G~ serous carcinoma G~ serous carcinoma Gj serous carcinoma G~ serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 endometrioid carcinoma G3 endometrioid carcinoma G~ endometrioid carcinoma G3 endometrioid carcinoma G3 endometfioid carcinoma G3 endometrioid carcinoma G3 endometrioid carcinoma G3 endometrioid carcinoma Fibrosarcoma Fibrosarcoma Mixed Mullerian tumor Mixed Mullerian tumor Krukenberg tumor Krukenberg tumor G3 adenocarcinoma G3 adenocarcinoma
18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
° ER, estrogen receptor (fmol/mg protein). b PR, progesterone receptor (fmol/mg protein). " G~, well-differentiated; G,, moderately well-differentiated; G3, poorly differentiated.
s p e c i m e n s w e r e t a k e n f r o m d i f f e r e n t p a r t s o f the t u m o r . In n i n e c a s e s e a c h site o f t u m o r w a s p o s i t i v e f o r E R a n d / o r P R , in 2 c a s e s ( P a t i e n t s 5 an d 7) o n e site w a s E R , P R p o s i t i v e , the o t h e r E R , P R n e g a t i v e , in t w o c a s e s ( P a t i e n t s 9 a n d 15) o n e site w a s E R p o s i t i v e a n d t he o t h e r E R n e g a t i v e , an d in t h r e e c a s e s ( P a t i e n t s 6, 10 a n d 14) o n e site w a s E R p o s i t i v e - P R p o s i t i v e an d t h e o t h e r E R positive-PR negative. Table 2 depicts the histology and r e c e p t o r results from each o v a r y w h e r e b i l a t e r a l t u m o r s w e r e p r e s e n t . O n l y six t u m o r s h ad i d e n t i c a l E R / P R s t a t u s , six w e r e p o s i t i v e f o r E R in o n e t u m o r b ut n o t t h e o t h e r , an d f o u r w e r e p o s i t i v e f o r P R in o n e t u m o r b u t n o t t h e o t h e r .
STEROID RECEPTOR VARIATION IN OVARIAN CANCER
427
TABLE 3 STEROID RECEPTORS IN PRIMARY AND METASTATIC TUMORS
Patient No.
ER a
33
0 0
34
11
35 36
37 38 39 40
5 211 64 76 61 15 0 0 12 0 18 0 34 657
PR b
Histologyc
0 0 31 0 39 0 0 0 0 0 0 8 0 9 0 7 81
Primary G2 serous carcinoma Omental deposit Primary G3 serous carcinoma Omental deposit Primary G3 serous carcinoma Omental deposit Primary G3 serous carcinoma Omental deposit Pelvic deposit Primary proliferating mucinous carcinoma Omental deposit Primary G~ adenocarcinoma Omental deposit Primary G2 mucinous carcinoma Omental deposit Primary malignant Mullerian tumor Uterine wall deposit
° ER, estrogen receptor (fmol/mg protein). b PR, progesterone receptor (fmol/mg protein). " G,, well-differentiated; Gz, moderately well-differentiated; G3, poorly differentiated.
Table 3 depicts the variation in receptor content between primary tumor and metastatic deposits. In one case (Patient 38) ER and in two cases (Patients 34 and 35) PR were present in the primary but not the metastatic tumor. The secondary tumor had higher ER, PR values in only one case (Patient 40) and in all other cases values in metastatic disease were similar to or less than the primary tumor.
DISCUSSION This study has been confined to specimens with identical histological type and differentiation and has demonstrated major differences in receptor status within the same anatomical site of disease, between bilateral tumors and between primary and metastatic disease. When receptors were analyzed from adjoining sites of the same tumor, receptor status was consistent in only 56% of cases while when receptor status was ascertained in bilateral tumors consistent findings were noted in only 38% of cases. More importantly, perhaps, was the difference observed in the receptor status of 50% of primary and metastatic tumors, which may imply a biological deregulation as tumors spread and has obvious important'implications for therapy. Nonetheless, it should be noted that the differences in receptor status related particularly to tumors in which receptors were present in small amounts, and if the cut-off value for positivity was raised to 30 fmol/mg protein, then consistent results would have been present in 70% of all cases analyzed. Furthermore, the exact location of steroid receptors in normal and malignant ovarian tissue has not been defined; in particular, the contribution of glandular
428
QUINN ET AL.
and stromal components to overall receptor status is unknown and, since the proportion of glands and stroma was not assessed in this study, then some of the variation in receptor content may be accounted for by differing amounts of glands and stroma within the paired tumor samples. Little attention has been paid in the literature to receptor variation, either within the primary or in metastatic disease or between primary and metastatic disease, and it may be that cases reported in which only metastatic disease has been assayed may not be representative of the primary tumor and vice versa. Holt et al. [4] noted only two ER positive metastases from six ER positive primary tumors and Galli et al. [5] reported on one patient whose primary serous tumor was PR negative but in whom a secondary uterine deposit was PR positive, while Schwartz et al. [6] found a quantative variation in ER within multiple sites of three primary ovarian carcinomas and a similar variation in ER between primary and metastatic cancer in eight cases. The steroid receptor values of the proliferating and malignant tumors reported in this study tended to be low with only 13 tumors having an ER value equal tO or greater than 30 fmol/mg protein, 4 having both ER and PR at this level, and 4 having PR alone at this level and this also could account for the discrepancy in response of these tumors to hormonal therapy, since in breast cancer, and probably in endometrial cancer [7], higher levels of receptors indicate a higher likelihood of response. It is recommended that when ovarian malignancies are assayed for receptors that, at least, both primary and secondary tumors be analyzed and, at best, multiple sites from both be analyzed, and where residual disease is to be left biopsies be taken for receptor analyses.
CONCLUSIONS I. Different sites within primary ovarian carcinoma have varying receptor profiles. 2. Bilateral ovarian tumours often have different receptor profiles. 3. Multiple sites of both primary and metastatic disease should be assayed before receptor status is assigned.
ACKNOWLEDGMENTS We are grateful to T. C. Bui and S. H. Koh who performed the assays. This study was supported by a grant from 3AW Research Foundation.
REFERENCES l. Quinn, M. A. ls endocrine status relevant to treatment planning in patients with gynaecological cancer? Attst. N. Z. J. Obstet. Gynaecol. 24, 153-157 (1984). 2. McGuire, W. L. An update on estrogen and progesterone receptors in prognosis of primary and advanced breast cancers, in H o r m o n e s and cancer (S. lacobelli et al., Eds.), Raven Press, New York, pp. 337-352 (1979). 3. Quinm M. A., Pearce, P., Rome~ R., Funder, J. W., Fortune, D. and Pepperell, R. J. Cytoplasmic steroid receptors in ovarian tumours, Brit. J. Obstet. Gynaecol. 89, 754-759 (1982). 4. Holt, J. A., Caputo, T. A., Kelly, K. M., Greenwald, P., and Chorost. S. Estrogen and progestin binding in cytosols of ovarian adenocarcinomas, Obstet. Gynecol. 53, 50-58 (1979).
STEROID RECEPTOR VARIATION IN OVARIAN CANCER
429
5. Galli, M. C., De Giovanni, C., Nicoletti, G., et al. The occurrence of multiple steroid hormone receptors in disease-free and neoplastic human ovary, Cancer (Amsterdam) 47, 1297-1302 (1981). 6. Schwartz, P. E., Li Volsi, V. A., Hildrerth, N., Machusky, N. J., Nafrolin, F. N., and Eisenfeld, A. J. Estrogen receptors in ovarian epithelial carcinoma, Obstet. Gynecol. 59, 229-238 (1982). 7. Quinn, M. A., Cauchi, M., and Fortune, D. Endometrial carcinoma: Steroid receptors and response to medroxyprogesterone acetate, Gynecol. Oncol. 21, 314-319 (1985).
Steroid Receptors and Ovarian Tumors: Variation within Primary Tumors and between Primary Tumors and Metastases M. A. QUINN,* R. M. ROME,-~ M. CAUCHI,'~ AND D. W. FORTUNEt .*University of Melbourne and ?Royal Women's Hospital. Melboarne, Aastralia Received April 2, 1987 Estrogen and progesterone receptors have been measured in primary and secondary ovarian carcinoma in eight patients, in bilateral ovarian tumors in 16 patients, and from multiple sites within the same tumor in 16 patients (12 primary and 4 secondary). In the majority of cases, metastatic tumors contained less receptors than their primary tumors. Marked variations in receptor content were noted within the same tumor and between bilateral tumors. This variation in receptor levels may explain the discrepancy between the presence of receptors and the response to hormonal treatment. Multiple sites of ovarian carcinoma need to be assayed for receptor content before a final decision can be made on receptor status. © 1988AcademicPress, Inc.
INTRODUCTION Approximately 65% of ovarian carcinomas contain estrogen receptors (ER) and 40% progesterone receptors yet only about 20% of patients respond to hormone therapy [1]. In breast cancer, however, the presence of ER and/or PR gives an excellent guide to response to hormonal manipulation [2]. This discrepancy between the presence of receptors and the response to endocrine therapy in patients with ovarian carcinoma may reflect the relatively low levels of receptors present or, in fact, may be due to a variation in receptor levels, either within the primary tumor or within metastatic disease, or both. We have investigated this latter possibility, by analyzing the receptor content of different sites within primary and metastatic tumors.
PATIENTS AND METHODS Tissue specimens from 39 cases of ovarian malignancy and 1 case of bilateral benign serous tumor were removed at the time of primary surgery and assay for E R and PR performed on either fresh tissue or tissue which had been previously frozen to -80°C in liquid nitrogen. Only nonnecrotic malignant tissue was taken -for analysis and adjoining specimens were used rather than specimens from different sites of the tumor. Assay methodology, using a multiple point analysis, was as described previously [3]. Histological examination was made on each tissue specimen and tumor type and grading of differentiation were ascertained. Receptor assays were performed only when samples were of uniform histological 424
0090-0258/88 $1.50 Copyright © 1988 by Academic Press. Inc. All rights of reproduction in any form reserved.
STEROID RECEPTOR VARIATION IN OVARIAN CANCER
425
TABLE 1 VARIATION IN RECEPTOR CONTENT WITHIN TUMORS
Patient No. 1 2 3 4 5 6
7 8 9 10 11 12 13 14 15 16
ER"
PR b
Histology"
0 0 23 39 207 133 211 71 49 0 6 15 8 15 0 0 0 0 334 17 7 49 37 223 149 162 96 23 21 26 0 7 10
95 96 14 9 14 12 39 9 29 0 0 20 0 12 0 6 21 0 0 13 0 66 32 27 30 18 8 0 8 45 8 0 0
Primary borderline muclnous tumor Primary borderline muclnous tumor Primary borderline mucmous tumor Primary borderline mucmous tumor Primary G, serous carcinoma Primary G~ serous carcinoma Primary Gs serous carcinoma Primary G3 serous carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G~ endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G2 endometrioid carcinoma Primary G~ endometrioid carcinoma Primary G3 adenocarcinoma Primary Gs adenocarcinoma Primary G3 adenocarcinoma Primary G3 adenocarcinoma Primary G~ adenocarcinoma Primary G3 adenocarcinoma " Primary malignant Mullerian tumor ' Primary malignant Mullerian tumor Omental deposit G~ serous carcinoma Omental deposit G~ serous carcinoma Omental deposit G3 serous carcinoma Omental deposit G3 serous carcinoma Omental deposit G 3 mucinous carcinoma Omental deposit G3 mucinous carcinoma Omental deposit G2 adenocarcinoma Omental deposit G2 adenocarcinoma
° ER, estrogen receptor (fmol/mg protein). b PR, progesterone receptor (fmol/mg protein). " G~, well-differentiated; G2, moderately well-differentiated; G3, poorly differentiated.
t y p e a n d g r a d i n g s i n c e b o t h t h e s e v a r i a b l e s m a y a f f e c t r e c e p t o r c o n t e n t [3]. A l e v e l o f 5 f m o l / m g p r o t e i n o r m o r e o f r e c e p t o r w a s t a k e n as a p o s i t i v e r e s u l t , all s a m p l e s f r o m e a c h p a t i e n t w e r e a n a l y z e d w i t h i n t h e o n e a s s a y . T h e w i t h i n a s s a y v a r i a t i o n w a s less t h a n 10% f o r all s a m p l e s .
RESULTS T ab l e 1 depicts the steroid r e c e p t o r levels and histology in 2 p r i m a r y proliferating m u c i n o u s t u m o r s , 10 p r i m a r y m a l i g n a n t t u m o r s , an d 4 m e t a s t a t i c t u m o r s w h e r e
426
QUINN ET AL. TABLE 2 STEROIDRECEPTORSIN BILATERALOVARIANTUMORS
Patient No.
ER a
PRb
Histology'
17
8 6 21 8 274 118 49 153 8 0 0 7 10 17 9 0 55 0 0 0 49 197 48 16 0 76 13 34 9 0 27 19
116 63 336 13 0 11 49 74 5 20 0 0 13 0 133 59 0 0 0 0 29 15 0 0 0 0 0 20 20 25 65 0
Benign serous Benign serous Proliferating serous Proliferating serous G~ serous carcinoma G~ serous carcinoma Gj serous carcinoma G~ serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 serous carcinoma G3 endometrioid carcinoma G3 endometrioid carcinoma G~ endometrioid carcinoma G3 endometrioid carcinoma G3 endometfioid carcinoma G3 endometrioid carcinoma G3 endometrioid carcinoma G3 endometrioid carcinoma Fibrosarcoma Fibrosarcoma Mixed Mullerian tumor Mixed Mullerian tumor Krukenberg tumor Krukenberg tumor G3 adenocarcinoma G3 adenocarcinoma
18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
° ER, estrogen receptor (fmol/mg protein). b PR, progesterone receptor (fmol/mg protein). " G~, well-differentiated; G,, moderately well-differentiated; G3, poorly differentiated.
s p e c i m e n s w e r e t a k e n f r o m d i f f e r e n t p a r t s o f the t u m o r . In n i n e c a s e s e a c h site o f t u m o r w a s p o s i t i v e f o r E R a n d / o r P R , in 2 c a s e s ( P a t i e n t s 5 an d 7) o n e site w a s E R , P R p o s i t i v e , the o t h e r E R , P R n e g a t i v e , in t w o c a s e s ( P a t i e n t s 9 a n d 15) o n e site w a s E R p o s i t i v e a n d t he o t h e r E R n e g a t i v e , an d in t h r e e c a s e s ( P a t i e n t s 6, 10 a n d 14) o n e site w a s E R p o s i t i v e - P R p o s i t i v e an d t h e o t h e r E R positive-PR negative. Table 2 depicts the histology and r e c e p t o r results from each o v a r y w h e r e b i l a t e r a l t u m o r s w e r e p r e s e n t . O n l y six t u m o r s h ad i d e n t i c a l E R / P R s t a t u s , six w e r e p o s i t i v e f o r E R in o n e t u m o r b ut n o t t h e o t h e r , an d f o u r w e r e p o s i t i v e f o r P R in o n e t u m o r b u t n o t t h e o t h e r .
STEROID RECEPTOR VARIATION IN OVARIAN CANCER
427
TABLE 3 STEROID RECEPTORS IN PRIMARY AND METASTATIC TUMORS
Patient No.
ER a
33
0 0
34
11
35 36
37 38 39 40
5 211 64 76 61 15 0 0 12 0 18 0 34 657
PR b
Histologyc
0 0 31 0 39 0 0 0 0 0 0 8 0 9 0 7 81
Primary G2 serous carcinoma Omental deposit Primary G3 serous carcinoma Omental deposit Primary G3 serous carcinoma Omental deposit Primary G3 serous carcinoma Omental deposit Pelvic deposit Primary proliferating mucinous carcinoma Omental deposit Primary G~ adenocarcinoma Omental deposit Primary G2 mucinous carcinoma Omental deposit Primary malignant Mullerian tumor Uterine wall deposit
° ER, estrogen receptor (fmol/mg protein). b PR, progesterone receptor (fmol/mg protein). " G,, well-differentiated; Gz, moderately well-differentiated; G3, poorly differentiated.
Table 3 depicts the variation in receptor content between primary tumor and metastatic deposits. In one case (Patient 38) ER and in two cases (Patients 34 and 35) PR were present in the primary but not the metastatic tumor. The secondary tumor had higher ER, PR values in only one case (Patient 40) and in all other cases values in metastatic disease were similar to or less than the primary tumor.
DISCUSSION This study has been confined to specimens with identical histological type and differentiation and has demonstrated major differences in receptor status within the same anatomical site of disease, between bilateral tumors and between primary and metastatic disease. When receptors were analyzed from adjoining sites of the same tumor, receptor status was consistent in only 56% of cases while when receptor status was ascertained in bilateral tumors consistent findings were noted in only 38% of cases. More importantly, perhaps, was the difference observed in the receptor status of 50% of primary and metastatic tumors, which may imply a biological deregulation as tumors spread and has obvious important'implications for therapy. Nonetheless, it should be noted that the differences in receptor status related particularly to tumors in which receptors were present in small amounts, and if the cut-off value for positivity was raised to 30 fmol/mg protein, then consistent results would have been present in 70% of all cases analyzed. Furthermore, the exact location of steroid receptors in normal and malignant ovarian tissue has not been defined; in particular, the contribution of glandular
428
QUINN ET AL.
and stromal components to overall receptor status is unknown and, since the proportion of glands and stroma was not assessed in this study, then some of the variation in receptor content may be accounted for by differing amounts of glands and stroma within the paired tumor samples. Little attention has been paid in the literature to receptor variation, either within the primary or in metastatic disease or between primary and metastatic disease, and it may be that cases reported in which only metastatic disease has been assayed may not be representative of the primary tumor and vice versa. Holt et al. [4] noted only two ER positive metastases from six ER positive primary tumors and Galli et al. [5] reported on one patient whose primary serous tumor was PR negative but in whom a secondary uterine deposit was PR positive, while Schwartz et al. [6] found a quantative variation in ER within multiple sites of three primary ovarian carcinomas and a similar variation in ER between primary and metastatic cancer in eight cases. The steroid receptor values of the proliferating and malignant tumors reported in this study tended to be low with only 13 tumors having an ER value equal tO or greater than 30 fmol/mg protein, 4 having both ER and PR at this level, and 4 having PR alone at this level and this also could account for the discrepancy in response of these tumors to hormonal therapy, since in breast cancer, and probably in endometrial cancer [7], higher levels of receptors indicate a higher likelihood of response. It is recommended that when ovarian malignancies are assayed for receptors that, at least, both primary and secondary tumors be analyzed and, at best, multiple sites from both be analyzed, and where residual disease is to be left biopsies be taken for receptor analyses.
CONCLUSIONS I. Different sites within primary ovarian carcinoma have varying receptor profiles. 2. Bilateral ovarian tumours often have different receptor profiles. 3. Multiple sites of both primary and metastatic disease should be assayed before receptor status is assigned.
ACKNOWLEDGMENTS We are grateful to T. C. Bui and S. H. Koh who performed the assays. This study was supported by a grant from 3AW Research Foundation.
REFERENCES l. Quinn, M. A. ls endocrine status relevant to treatment planning in patients with gynaecological cancer? Attst. N. Z. J. Obstet. Gynaecol. 24, 153-157 (1984). 2. McGuire, W. L. An update on estrogen and progesterone receptors in prognosis of primary and advanced breast cancers, in H o r m o n e s and cancer (S. lacobelli et al., Eds.), Raven Press, New York, pp. 337-352 (1979). 3. Quinm M. A., Pearce, P., Rome~ R., Funder, J. W., Fortune, D. and Pepperell, R. J. Cytoplasmic steroid receptors in ovarian tumours, Brit. J. Obstet. Gynaecol. 89, 754-759 (1982). 4. Holt, J. A., Caputo, T. A., Kelly, K. M., Greenwald, P., and Chorost. S. Estrogen and progestin binding in cytosols of ovarian adenocarcinomas, Obstet. Gynecol. 53, 50-58 (1979).
STEROID RECEPTOR VARIATION IN OVARIAN CANCER
429
5. Galli, M. C., De Giovanni, C., Nicoletti, G., et al. The occurrence of multiple steroid hormone receptors in disease-free and neoplastic human ovary, Cancer (Amsterdam) 47, 1297-1302 (1981). 6. Schwartz, P. E., Li Volsi, V. A., Hildrerth, N., Machusky, N. J., Nafrolin, F. N., and Eisenfeld, A. J. Estrogen receptors in ovarian epithelial carcinoma, Obstet. Gynecol. 59, 229-238 (1982). 7. Quinn, M. A., Cauchi, M., and Fortune, D. Endometrial carcinoma: Steroid receptors and response to medroxyprogesterone acetate, Gynecol. Oncol. 21, 314-319 (1985).