Expression of cathepsin D and estrogen receptor in male breast carcinoma

doi:10.1016/0046-8177(93)90293-P

Human Pathology

Volume 24, Issue 2, February 1993, Pages 148-151

https://doi.org/10.1016/0046-8177(93)90293-P Get rights and content

Abstract

Male breast cancer is probably hormone dependant, but studies are few due to the rarity of this tumor. We have studied 21 cases of male breast cancer immunohistologically for estrogen receptor (ER) and cathepsin D (CD) expression. In carcinoma of the female breast ER expression is associated with longer patient survival and responsiveness to hormonal manipulation. Cathepsin D is an estrogen-regulated lysosomal protease with proteolytic and mitogenic properties whose presence denotes a functioning ER. In our series of male breast carcinomas 86% were ER positive and 62% were CD positive; this compares with typical figures of 50% and 66%, respectively, for female breast cancer. We observed no trends between expression of ER and CD and patient survival; immunostaining for ER and CD is unlikely to be clinically useful in carcinoma of the male breast. The high rate of ER positivity in males suggests that male and female breast carcinomas are biologically different tumors.

References (28)

A Howell et al.
Steroid hormone receptors and survival after first relapse in breast cancer
Lancet
(1984)
M Morisset et al.
The 52-kDa estrogen induced protein is a lysosomal acidic protease
Biochem Biophys Res Commun
(1986)
F Spyratos et al.
Cathepsin D: An independent prognostic factor for metastasis of breast cancer
Lancet
(1989)
G Granata et al.
Prognostic relevance of cathepsin D versus oestrogen receptors in node negative breast cancers
Eur J Cancer
(1991)
SG Korenman
The endocrinology of the abnormal male breast
Ann N Y Acad Sci
(1986)
LH Sobin et al.
Relation between male breast cancer and prostate cancer
Br J Cancer
(1980)
DP Rose
Endocrine epidemiology of male breast cancer
Anticancer Res
(1988)
JA Henry et al.
Prognostic significance of the estrogen regulated protein, cathepsin D, in breast cancer
Cancer
(1990)
WA Reid et al.
Immunolocalisation of cathepsin D in normal and neoplastic human tissues
J Clin Pathol
(1986)
BR Westley et al.
Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cell lines
Nucleic Acids Res
(1987)

B Westley et al.

Estradiol induced proteins in the MCF 7 human breast cancer cell line

Biochem Biophys Res Commun

(1979)

L Cheng et al.

Demonstration of oestrogen receptors by monoclonal antibody in formalin fixed breast tumours

Lab Invest

(1988)

DD Giri et al.

Oestrogen receptors in benign breast epithelial lesions and intraduct carcinoma of the breast: An immunohistological study

Histopathology

(1989)

F Capony et al.

Increased secretion, altered processing and glycosylation of pro-cathepsin D in human mammary cancer cells

Cancer Res

(1989)

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Male breast cancer has traditionally been compared with female breast cancer, using the same staging system and prognostic indicators. A variety of histochemical and pathologic factors commonly used in node-negative female breast cancer were applied to 18 node-negative male breast cancers to assess their relevance to survival.
A slide review was performed for nuclear grade, lymphocytic infiltration, and lymphatic and vascular invasion. Flow cytometry was available on all the specimens. Immunohistochemistry was used to assess p53, estrogen receptors (ERs), cathepsin D, Ki-67, and c-erbB-2 (HER2/neu). A clinical correlation was performed based on chart reviews and phone interviews, recording demographics, treatment, and long-term survival.
The average age at diagnosis was 64 years (range, 34-85 years). There were 15 T1 lesions, 2 T2 lesions, and 1 T3 lesion. All patients had a modified radical mastectomy. None received radiation therapy. The mean follow-up was 73 months. Three patients died of their disease (17.6%), 2 patients died from unrelated reasons, 1 patient was lost to follow-up, and the other 12 patients are alive with no evidence of disease. The actuarial 5-year survival was 83%. Estrogen receptor and HER2/neu overexpression were significantly more predominant in male breast cancer than in female breast cancer. Estrogen receptor positivity was present in 17 of 18 patients and HER2/neu overexpression in 10 of 18. A positive ER status and overexpression of cathepsin or p53 were correlated with a better survival, but only ER (P = 0.026) and p53 (P = 0.023) reached statistical significance.
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The differential diagnosis for breast problems in male patients is generally simpler than in female patients because the spectrum of common diagnoses is narrower in males than in females. Mammography in male patients is performed infrequently even in busy breast imaging practices, making up less than 1% of mammographic studies performed in 2003 at the Baylor Sammons Breast Imaging Center at Baylor University Medical Center in Dallas. Despite the infrequency of the examinations, radiologists need to be familiar with the mammographic appearances of the normal and abnormal male breast to render accurate interpretations, and clinicians need to be familiar with the common diagnoses seen in men with breast complaints. The objective of this article is to review male breast disorders encountered by clinicians and radiologists.
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We conducted an analysis on 41 cases of male breast cancer (median age 54 y; range 25–82 y) in Kuwait. Most (51%) were stage II cancers with 65% arising in the left breast. There were 5 (12%) T₁tumours, 23 (56%) T₂tumours and 13 (32%) T₃/T₄tumours. They were mostly (95%) infiltrating ductal carcinomas; 97% were grade 2 or 3. Axillary lymph node involvement was found in 69%. Estimated 5-year survival rates were 67% and 58% for overall and relapse free survival respectively. Favourable prognosis was associated with age below 50y, clinical stage I and II, small tumour size (T₁, T₂), low tumour grade and absence of nodal involvement or distant metastases; nodal status and grade were independent factors for relapse free survival in multivariate analysis. In 18 cases, an immunohistochemical study showed some degree of tumour antigen reaction for ER in 89% of cases, PR in 61%, pS2 in 44%, CathD in 72%, p53 in 56%, c-erbB-2 in 50%, Ki67 and PCNA in 100% and bcl-2 in 78%. There were significant associations between several of these factors but none influenced survival. Despite the high incidence of staining of ER, our data do not support the concept of an endocrine pathway that could be usefully antagonized with antioestrogens for therapeutic benefit, as in women.
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Aromatization or in situ estrogen production by aromatase has been considered to play an important role in the development of human breast carcinoma. In the human breast, aromatase overexpression is observed in the stromal or interstitial cells of the carcinoma, especially at the sites of frank invasion and/or adipose tissue. Transplantation experiments in the nude mouse employing MCF-7 and/or SF-TY human fibroblast cell lines revealed that aromatase activity and expression were much higher in the tumour with MCF-7 and SF-TY than that with MCF-7 alone. Aromatase overexpression in human breast carcinoma tissue is considered to occur as a result of carcinomastromal cell interactions, i.e. paracrine communication between stromal and carcinoma cells. Aromatase overexpression is correlated with the malignant phenotype in the human breast, but not with stage, age, clinical stages, clinical course, or proliferative activity of breast carcinoma. Aromatase overexpression may be correlated with development, rather than the biological behaviour of breast malignancy. Aromatase overexpression is not necessarily correlated with expression of 17β-hydroxysteroid dehydrogenase type 1, which converts estrone to estradiol and estrogen receptor. Different mechanisms may be involved in the regulation of expression of these two important estrogen-metabolizing enzymes and estrogen receptor in human breast cancer. Aromatase overexpression in intratumoral stromal cells was much more frequently detected in male breast cancer than in female counterparts, which confers a growth advantage on cancer cells in a male hormonal environment with low serum estrogen levels.
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Estrogen, through estrogen receptors (ERs), may regulate the synthesis of progesterone receptors (PRs) and of a heat shock estrogen receptor-associated protein (hsp27). In female breast carcinoma (FBC) both proteins serve as surrogate indicators for the presence of functional ERs. In addition, the expression of these proteins was related to other prognostic indicators of value in female breast tumours. Endocrine disorders, hormone therapy and altered estrogen metabolism have been associated with the development of male breast cancer (MBC), suggesting that evaluation of the expression of ER, PR and hsp27 might improve our understanding of the biology of this tumour. ER and PR status and hsp27 expression were evaluated by immunohistochemistry in 16 primary MBC patients. The interrelationships between these parameters were established and compared with the clinicopathological data on the tumours. Ten (56%) MBC patients were ER-positive, 69% were PR-positive and all samples were hsp27-positive. Our series of MBC patients showed a positive correlation between ERs and PRs, however there was a lack of correlation between hsp27 and ERs or PRs. MBCs did not exhibit any correlation between the biomarkers studied and known prognostic indicators for females (e.g. Scarff-Bloom-Richardson (SBR) or modified SBR (MSBR) grade, T stage, lymph node status). This is the first published series reporting the incidence of hsp27 in MBC. The lack of association between the expression of ERs and hsp27 found in MBC differs from the results reported for FBC, moreover the expression of ERs, PRs or hsp27 did not correlate with the clinicopathological parameters that have prognostic value in females. Although the data were obtained from a relatively small sample population, our findings suggest that MBC and FBC are biologically different tumours with respect to the expression of the studied proteins.
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Original contributionExpression of cathepsin D and estrogen receptor in male breast carcinoma

Abstract

Lancet

Biochem Biophys Res Commun

Lancet

Eur J Cancer

The endocrinology of the abnormal male breast

Ann N Y Acad Sci

Relation between male breast cancer and prostate cancer

Br J Cancer

Endocrine epidemiology of male breast cancer

Anticancer Res

Prognostic significance of the estrogen regulated protein, cathepsin D, in breast cancer

Cancer

Immunolocalisation of cathepsin D in normal and neoplastic human tissues

J Clin Pathol

Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cell lines

Nucleic Acids Res

Estradiol induced proteins in the MCF 7 human breast cancer cell line

Biochem Biophys Res Commun

Demonstration of oestrogen receptors by monoclonal antibody in formalin fixed breast tumours

Lab Invest

Oestrogen receptors in benign breast epithelial lesions and intraduct carcinoma of the breast: An immunohistological study

Histopathology

Increased secretion, altered processing and glycosylation of pro-cathepsin D in human mammary cancer cells

Cancer Res

Original contribution
Expression of cathepsin D and estrogen receptor in male breast carcinoma