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Correlation between histopathologic features and estrogen receptor status in primary breast cancer
ht. J. Gynaecol Obstet., International Federation
1984, 22: 117-119 of Gynaecology & Obstetrics
177
CORRELATION BETWEEN HISTOPATHOLOGIC STATUS IN PRIMARY BREAST CANCER
H. MANTOUVALOS, Obstetric
A. MAKRYGIANNAKIS,
and Gynecologic
(Received (Accepted
C. METALLINOS,
Clinic, Piraeus General Hospital.
FEATURES
A. YIANNIOU
AND ESTROGEN
RECEPTOR
and A. GOUSKOS
Piraeus, Greece
December 27th, 1983) January 4th, 1984)
Abstract Mantouvalos H. Makrygiannakis A. Metallinos C, Yianniou A. Gouskos A (Obstetric and Gy,necologic Clinic. Piraeus General Hospital. Piraetrs. Greece). Correlation between histopathologic features and estrogen receptor status in primaryS breast cancer. lnt J Gy,naecol Obstet 22: 1 77-J To,1 984 Relationships between certain histopathologic ,features of’ tumor specimens and estrogen receptor (ER) status were investigated. Lobular and drtctal carcinomas were found to be richer in ER than other histologic types, Well dijjerentiated carcinomas were more often hormone receptor positive than poorly differentiated tumors. L ymphocy tic and plasmatot:ytic’ infiltration in and around the tumor as w?ell as elastosis also appeared to be related positively- to ER status.
Keywords: Breast cancer; Pathology; Estrogen receptor; Tumor specimens and estrogen receptor status; Regress; Hormone manipulation. Introduction In the last decade many studies have shown that more than half of mammary carcinomas contain insufficient amount of ER sites [4]. Further studies have proven that when ERs are present in neoplastic cells there is great probability that they will regress in response 0020-7292/84/$03.00 0 1984 International Federation Published and Printed in Ireland
to hormone manipulation such as ovariectomy, adrenalectomy (medical or surgical), hypophysectomy or administration of hormones [ 3,5,10,12]. However, the determination of the ER content of a tumor is still not an easy every day procedure for many centers, especially in the developing world. We have tried to add in the field of the breast cancer knowledge the correlation between the “classical” profile of a breast tumor, i.e. its histopathologic picture and the “harmonic” profile, i.e. the ER content. Material and methods Breast cancer specimens from women presenting with primary breast cancer at various stages were examined, All specimens were kept initially at -20°C and later transported to the laboratory and stored at -70°C for longer periods. The tissue specimens were processed and assayed for ER using the method of dextran coated charcoal as described previously [9, 131. Histopathologic analysis was performed in 33.5 sections of the tumor, in the same area from which samples for the ER-assay had been taken. Tumors were classified and graded in three groups in accordance with Azzopardi [ 11. Grade I, well differentiated; grade II, intermediate: grade 111, the least differentiated. Lymphocytic and plasmatocytic infiltration was categorized into 4 grades: minimal (+), mild (+ +), moderate (+ + + ) and intense (+ + + + ). Int J G,vnaccol Obstet 2,
of Gynaecology
and Obstetrics
178
Marltoui~alos et al.
Table I. ER content in relation to tumor histologic type. Type of carcinoma
No.
Ductal Lobular
134 27
114 20
85 14
20 I
15 26
10 7 2
4 3 0
40 43 0
6 4 2
60 57 100
9
8
89
1
11
Medullary Tubular Inflammatory Mucoid
ER+
510 ER-
%
Statistical evaluation
Table 111. ER content in relation plasmatocytic infiltration.
to lymphocytic
ER+
%
ER-
%
P> 0.1
Lymphocytic and No. plasmatocytic infiltration
P < 0.001
+ ++t
12 84 21
57 56 12
19 61 51
15 28 9
21 33 43
+t++
12
3
25
9
15
++
and
Statistical evaluation
P < 0.1
The tumors were graded according to the amount of elastosis into categories 0, 1, 2, in paraffin sections, using a modified Gomori aldehyde-Fuchsin stain as described by Shivas and Douglas [ 141. In category 0 tumors, elastosis was not demonstrable; in category 1 tumors, it was present to a small or moderate degree; in category 2 tumors, there was a gross amount of elastosis. Results The results are summarized in Tables I-IV. Ductal carcinomas appear to be the richest in ER content, if the very few mucous carcinomas are excluded. Myeloid and inflammatory are the poorest. The difference between ductal and lobular carcinomas is not significant (P > 0.1) but each of the above differs significantly (P < 0.001) from the other types. The difference between carcinomas of grade I and II is not significant (P > 0.1) but seems to become more significant between grade II and III (P < 0.05). Table III shows that there is a negative correlation between cellular infiltra-
tion and ER content but there is not any statistical significance. Table IV shows that there is a rather significant positive correlation (P < 0.01) between elastosis and ER content. Discussion Our results seem to show some correlation between ER status and pathologic features. The most useful index is the pathologic type of tumor. Three out of four lobular carcinomas in our series were found to contain sufficient ER and this occurred in more than four out of five cases when the carcinoma was ductal. When the tumor was grade I with maximal elastosis and minimal cellular infiltration the possibility for a tumor to be ER positive was around 80%. Our results confirm the findings of other workers that certain pathologic features can be correlated in various degrees with ER status and subsequently with longer remission and disease-free interval [2,6-g, 11 I. However, there was in our series a significant number of patients who were ER negaTable IV. ER content according to the degree of elastosis. Grade of elastosis
Table II. ER content in relation to tumor grade. Grade
I
No,
52
ER+
38
%
73
ER-
14
%
Statistical evaluation
ER+
%
ER-
%
38
13
34
25
66
1 (small to moderate)
10s
57
54
48
46
2 (Abundant)
46
37
80
9
20
0 (not demonstrable)
No.
P < 0.05
21 P > 0.1
II
88
57
65
31
35
111
49
24
49
25
51
P < 0.01
P < 0.05
Int J Gynaecol
Obstet 22
Statistical evaluation
Histopathology and estrogen receptors
tive in the lower grade tumors (27%) with little or no lymphocytic or plasmatocytic infiltration (2 1%) and with maximal elastosis (20%). Therefore, one must emphasize that the histopathologic features cannot replace the receptor status, the knowledge of which is really very important for the establishment of the adequate therapy. On the other hand, if a receptor status is not available, as can happen especially in developing countries, then adequate pathologic examination of the specimen provides a good projective index for response to hormone endocrine therapy and may lead to a more rational approach to treatment selection. References Azzopardi GJ: Problems in breast pathology. Vol II In Major Problems in Pathology, Vol II, p 240. W.B. Saunders, Philadelphia, 1979. Champion PH, Wallace IWI, Prescott JR: Histology in breast cancer prognosis. Br J Cancer 26: 129, 1972. Gapinski VP, Donegan LW: Estrogen receptors and breast cancer: prognostic and therapeutic implications. Surgery 88. 386,198O. Jensen EV, De Sombre ER: Mechanism of action of the female sex hormones. Annu Rev Biochem 41: 203, 1972. Lippman EM, Allegre CJ: Quantitative estrogen receptor analyses: The response to endocrine and cytotoxic chemotherapy in human breast cancer and the disease-free interval. Cancer 46: 2829, 1980.
179
6 King BJR: Analysis of estradiol and progesterone receptors in early and advanced breast tumors. Cancer 46: 2818,198O. 7 Masters WRS, Sangster K, Hawkins AR, Shivas AA: Elastosis and oestrogen receptors in human breast cancer. Br J Cancer 33: 342,1976. 8 Masters WRJ, Millis RR, King BJR, Rubens DR: Elastosis and response to endocrine therapy in human breast cancer. Br J Cancer 39: 536,1979. 9 McGuire WL, DeLaGarza MJ: Improved sensitivity in the measurement of estrogen receptor in human breast cancer. Clin Endocrinol Metab 37: 386, 1973. 10 McGuire WL, Carbone PP, Sears ME, Escher GC: Estro-
11
12
13
14
gen receptors in human breast cancer: an overview. In Estrogen Receptors in Human Breast Cancer (eds WI McGuire, PP Carbone, EP Volmer), p 1. Paven Press, New York, 1975. Millis RR: Correlation of hormone receptors with pathological features in human breast cancer. Cancer 46: 2869, 1980. Osborn Kent C, Yochmowitz GM, Knight AW, McGuire LW: The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46: 2884, 1980. Rich MA, Furmanski P, Brooks SC: Prognostic value of estrogen receptor determinations in patients with breast cancer. Cancer Res 38: 4926, 1978. significance of Shivas AA, Douglas JG: The prognostic elastosis in breast carcinoma. J R Co11Surg Edinburgh 17:
315,1972. Address for reprints: Dr. H. Mantouvalos Consultant Obstetrics and Gynecology Piraeus General Hospital Piraeus, Greece
1tlt J G),naecol Obstet 22
1984, 22: 117-119 of Gynaecology & Obstetrics
177
CORRELATION BETWEEN HISTOPATHOLOGIC STATUS IN PRIMARY BREAST CANCER
H. MANTOUVALOS, Obstetric
A. MAKRYGIANNAKIS,
and Gynecologic
(Received (Accepted
C. METALLINOS,
Clinic, Piraeus General Hospital.
FEATURES
A. YIANNIOU
AND ESTROGEN
RECEPTOR
and A. GOUSKOS
Piraeus, Greece
December 27th, 1983) January 4th, 1984)
Abstract Mantouvalos H. Makrygiannakis A. Metallinos C, Yianniou A. Gouskos A (Obstetric and Gy,necologic Clinic. Piraeus General Hospital. Piraetrs. Greece). Correlation between histopathologic features and estrogen receptor status in primaryS breast cancer. lnt J Gy,naecol Obstet 22: 1 77-J To,1 984 Relationships between certain histopathologic ,features of’ tumor specimens and estrogen receptor (ER) status were investigated. Lobular and drtctal carcinomas were found to be richer in ER than other histologic types, Well dijjerentiated carcinomas were more often hormone receptor positive than poorly differentiated tumors. L ymphocy tic and plasmatot:ytic’ infiltration in and around the tumor as w?ell as elastosis also appeared to be related positively- to ER status.
Keywords: Breast cancer; Pathology; Estrogen receptor; Tumor specimens and estrogen receptor status; Regress; Hormone manipulation. Introduction In the last decade many studies have shown that more than half of mammary carcinomas contain insufficient amount of ER sites [4]. Further studies have proven that when ERs are present in neoplastic cells there is great probability that they will regress in response 0020-7292/84/$03.00 0 1984 International Federation Published and Printed in Ireland
to hormone manipulation such as ovariectomy, adrenalectomy (medical or surgical), hypophysectomy or administration of hormones [ 3,5,10,12]. However, the determination of the ER content of a tumor is still not an easy every day procedure for many centers, especially in the developing world. We have tried to add in the field of the breast cancer knowledge the correlation between the “classical” profile of a breast tumor, i.e. its histopathologic picture and the “harmonic” profile, i.e. the ER content. Material and methods Breast cancer specimens from women presenting with primary breast cancer at various stages were examined, All specimens were kept initially at -20°C and later transported to the laboratory and stored at -70°C for longer periods. The tissue specimens were processed and assayed for ER using the method of dextran coated charcoal as described previously [9, 131. Histopathologic analysis was performed in 33.5 sections of the tumor, in the same area from which samples for the ER-assay had been taken. Tumors were classified and graded in three groups in accordance with Azzopardi [ 11. Grade I, well differentiated; grade II, intermediate: grade 111, the least differentiated. Lymphocytic and plasmatocytic infiltration was categorized into 4 grades: minimal (+), mild (+ +), moderate (+ + + ) and intense (+ + + + ). Int J G,vnaccol Obstet 2,
of Gynaecology
and Obstetrics
178
Marltoui~alos et al.
Table I. ER content in relation to tumor histologic type. Type of carcinoma
No.
Ductal Lobular
134 27
114 20
85 14
20 I
15 26
10 7 2
4 3 0
40 43 0
6 4 2
60 57 100
9
8
89
1
11
Medullary Tubular Inflammatory Mucoid
ER+
510 ER-
%
Statistical evaluation
Table 111. ER content in relation plasmatocytic infiltration.
to lymphocytic
ER+
%
ER-
%
P> 0.1
Lymphocytic and No. plasmatocytic infiltration
P < 0.001
+ ++t
12 84 21
57 56 12
19 61 51
15 28 9
21 33 43
+t++
12
3
25
9
15
++
and
Statistical evaluation
P < 0.1
The tumors were graded according to the amount of elastosis into categories 0, 1, 2, in paraffin sections, using a modified Gomori aldehyde-Fuchsin stain as described by Shivas and Douglas [ 141. In category 0 tumors, elastosis was not demonstrable; in category 1 tumors, it was present to a small or moderate degree; in category 2 tumors, there was a gross amount of elastosis. Results The results are summarized in Tables I-IV. Ductal carcinomas appear to be the richest in ER content, if the very few mucous carcinomas are excluded. Myeloid and inflammatory are the poorest. The difference between ductal and lobular carcinomas is not significant (P > 0.1) but each of the above differs significantly (P < 0.001) from the other types. The difference between carcinomas of grade I and II is not significant (P > 0.1) but seems to become more significant between grade II and III (P < 0.05). Table III shows that there is a negative correlation between cellular infiltra-
tion and ER content but there is not any statistical significance. Table IV shows that there is a rather significant positive correlation (P < 0.01) between elastosis and ER content. Discussion Our results seem to show some correlation between ER status and pathologic features. The most useful index is the pathologic type of tumor. Three out of four lobular carcinomas in our series were found to contain sufficient ER and this occurred in more than four out of five cases when the carcinoma was ductal. When the tumor was grade I with maximal elastosis and minimal cellular infiltration the possibility for a tumor to be ER positive was around 80%. Our results confirm the findings of other workers that certain pathologic features can be correlated in various degrees with ER status and subsequently with longer remission and disease-free interval [2,6-g, 11 I. However, there was in our series a significant number of patients who were ER negaTable IV. ER content according to the degree of elastosis. Grade of elastosis
Table II. ER content in relation to tumor grade. Grade
I
No,
52
ER+
38
%
73
ER-
14
%
Statistical evaluation
ER+
%
ER-
%
38
13
34
25
66
1 (small to moderate)
10s
57
54
48
46
2 (Abundant)
46
37
80
9
20
0 (not demonstrable)
No.
P < 0.05
21 P > 0.1
II
88
57
65
31
35
111
49
24
49
25
51
P < 0.01
P < 0.05
Int J Gynaecol
Obstet 22
Statistical evaluation
Histopathology and estrogen receptors
tive in the lower grade tumors (27%) with little or no lymphocytic or plasmatocytic infiltration (2 1%) and with maximal elastosis (20%). Therefore, one must emphasize that the histopathologic features cannot replace the receptor status, the knowledge of which is really very important for the establishment of the adequate therapy. On the other hand, if a receptor status is not available, as can happen especially in developing countries, then adequate pathologic examination of the specimen provides a good projective index for response to hormone endocrine therapy and may lead to a more rational approach to treatment selection. References Azzopardi GJ: Problems in breast pathology. Vol II In Major Problems in Pathology, Vol II, p 240. W.B. Saunders, Philadelphia, 1979. Champion PH, Wallace IWI, Prescott JR: Histology in breast cancer prognosis. Br J Cancer 26: 129, 1972. Gapinski VP, Donegan LW: Estrogen receptors and breast cancer: prognostic and therapeutic implications. Surgery 88. 386,198O. Jensen EV, De Sombre ER: Mechanism of action of the female sex hormones. Annu Rev Biochem 41: 203, 1972. Lippman EM, Allegre CJ: Quantitative estrogen receptor analyses: The response to endocrine and cytotoxic chemotherapy in human breast cancer and the disease-free interval. Cancer 46: 2829, 1980.
179
6 King BJR: Analysis of estradiol and progesterone receptors in early and advanced breast tumors. Cancer 46: 2818,198O. 7 Masters WRS, Sangster K, Hawkins AR, Shivas AA: Elastosis and oestrogen receptors in human breast cancer. Br J Cancer 33: 342,1976. 8 Masters WRJ, Millis RR, King BJR, Rubens DR: Elastosis and response to endocrine therapy in human breast cancer. Br J Cancer 39: 536,1979. 9 McGuire WL, DeLaGarza MJ: Improved sensitivity in the measurement of estrogen receptor in human breast cancer. Clin Endocrinol Metab 37: 386, 1973. 10 McGuire WL, Carbone PP, Sears ME, Escher GC: Estro-
11
12
13
14
gen receptors in human breast cancer: an overview. In Estrogen Receptors in Human Breast Cancer (eds WI McGuire, PP Carbone, EP Volmer), p 1. Paven Press, New York, 1975. Millis RR: Correlation of hormone receptors with pathological features in human breast cancer. Cancer 46: 2869, 1980. Osborn Kent C, Yochmowitz GM, Knight AW, McGuire LW: The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 46: 2884, 1980. Rich MA, Furmanski P, Brooks SC: Prognostic value of estrogen receptor determinations in patients with breast cancer. Cancer Res 38: 4926, 1978. significance of Shivas AA, Douglas JG: The prognostic elastosis in breast carcinoma. J R Co11Surg Edinburgh 17:
315,1972. Address for reprints: Dr. H. Mantouvalos Consultant Obstetrics and Gynecology Piraeus General Hospital Piraeus, Greece
1tlt J G),naecol Obstet 22