Immunohistochemistry of a gross cystic disease fluid protein (GCDFP-15) of the breast. A marker of apocrine epithelium and breast carcinomas with apocrine features.

Gross cystic disease fluid is a pathologic secretion from breast composed of several glycoproteins, including a unique 15,000-dalton monomer protein, GCDFP-15. By the immunoperoxidase technique, GCDFP-15 was localized in the apocrine metaplastic epithelium lining breast cysts and in apocrine glands in the axilla, vulva, eyelid, and ear canal. In normal breast tissue, a few individual epithelial cells within lobules and small ducts were focally positive for GCDFP-15. Fourteen of 30 breast carcinomas stained positively for GCDFP-15. Of 16 carcinomas with apocrine features, 12 stained positively. Benign and malignant lesions from other tissues, including lung, colon, ovary, endometrium, stomach, prostate, liver, esophagus, and kidney, revealed no immunoreactivity. The only cells of "non-apocrine" tissues that contained GCDFP-15 were serous cells of the submandibular salivary gland, submucosal glands of the bronchi, and accessory lacrimal glands. Phylogenetically, these tissues have biologic features in common with apocrine glands. This report is the first to characterize GCDFP-15 as a specific tissue marker of apocrine epithelium.     

Apocrine epithelium of the breast: does it result from metaplasia?

 Benign and malignant breast lesions may show an apocrine epithelium considered to be the result of metaplasia. In an attempt to clarify the histogenesis of the breast apocrine epithelium we searched for the presence of apocrine cells or cells with apocrine differentiation during human breast development. We analysed 10 autopsy specimens of female breasts from fetuses between 28 and 40 weeks of gestational age and tissue from 6 normal breasts, obtained after breast reduction in nulliparous young women between 22 and 28 years of age. Formalin-fixed, paraffin-embedded sections were stained with haematoxylin-eosin, PAS-diastase and a monoclonal antibody (BRST-2) anti-GCDFP-15, which is a specific apocrine marker. A 40-week fetal breast was analysed by electron microscopy. No cells with histological and ultrastructural apocrine features were found in the ducts of fetal breasts. All fetal breasts showed some ducts with sparse GCDFP-15-immunoreactive cells; the number of these cells increased with gestational age. PAS-diastase was negative. No cells with apocrine morphology were found in ducts and lobules of normal adult breasts. Scattered GCDFP-15-positive luminal epithelial cells and rare PAS-diastase-positive cells were observed in some lobules of all adult breasts. Cells with biochemical characteristics (GCDFP-15 expression) of apocrine differentiation are evident during human fetal breast development and persist in adult mammary glands. Unknown stimuli may induce these cells to take on an apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than metaplasia. We suggest the term ”apocrine differentiation precursor cells” for GCDFP-15-positive breast epithelial cells with no apocrine morphology. Received: 14 February 1997 / Accepted: 12 April 1997     

Signet ring cells in breast carcinoma. An immunohistochemical and ultrastructural study.

Two cases of breast carcinoma composed predominantly of neoplastic cells with a signet ring appearance, one a case of invasive lobular carcinoma (ILC) and the other a case of invasive ductal carcinoma (IDC), were examined electron microscopically and immunohistochemically. In signet ring cells in the ILC, mucin was demonstrated ultrastructurally in the intracytoplasmic lumina and also to a small degree in the cytoplasmic mucous granules, whereas in signet ring cells in the IDC, mucin was found only in the cytoplasmic mucous granules. Immunohistochemically, signet ring cells in the ILC were intensely positive for gross cystic disease fluid protein (GCDFP-15), but those in the IDC showed no immunoreaction for GCDFP-15. Thus ultrastructural features and GCDFP-15 immunoreactivity appear to be useful for distinguishing between the two different types of signet ring cells.     

Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid protein-15 as markers of apocrine carcinoma of the breast

Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine marker; however, its expression was recently found to decrease in infiltrating, larger, or metastasizing apocrine carcinomas of the breast. In the breast, monoclonal antibody (MAb) B72.3 has been reported to be useful as an apocrine marker although it is used for that purpose much less frequently than GCDFP-15. In the search for a more consistent apocrine marker, immunoreactivity for MAb B72.3 was examined in apocrine carcinomas at different stages and compared with GCDFP-15. 47 of 51 apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas (15%) were MAb B72.3 positive, while 39 of 51 apocrine carcinomas (76%) and 13 of 62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3 exhibited positivity irrespective of infiltrating status, tumor size, or metastatic status. There was no correlation between MAb B72.3-immunoreactivity and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful to confirm the diagnosis of apocrine carcinoma, especially for advanced tumors, with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these two cases should be differentiated from ordinary apocrine carcinomas remains to be investigated.     

Immunohistochemical localization of gross cystic disease fluid protein-15, -24 and -44 in ductal carcinoma in situ of the breast: relationship to the degree of differentiation

AIMS: Three major proteins present in breast gross cystic disease fluid and expressed by the cyst lining apocrine epithelium are gross cystic disease fluid protein-15 (GCDFP-15), apolipoprotein-D (APO-D; GCDFP-24) and zinc alpha2-glycoprotein (ZnGP; GCDFP-44). The aim of this study was to investigate the expression of these proteins in ductal carcinoma in situ (DCIS) of the breast and to relate their expression with the degree of differentiation of DCIS. METHODS AND RESULTS: An immunohistochemical study of these proteins was performed in 57 cases of DCIS and nine cases of morphologically apocrine DCIS. Positivity was seen in 24/57 (42.1%) cases with anti-GCDFP-15, 20/57 (35.1%) cases with anti-GCDFP-24 and 22/57 (38.6%) cases with anti-GCDFP-44. GCDFP-15 positivity was noted in 5/13 (38.5%) of the well-differentiated, 11/19 (57.9%) intermediately differentiated and 8/25 (32.0%) of the poorly differentiated cases (P=0.217). GCDFP-24 positivity was seen in 3/13 (23.0%) well-differentiated, 9/19 (47.4%) intermediately differentiated and 8/25 (32.0%) poorly differentiated cases (P=0.336). GCDFP-44 was detected in 5/13 (38.5%) of well-differentiated cases, 11/19 (57.9%) intermediately differentiated and 6/25 (24.0%) poorly differentiated cases (P=0.074). In the nine cases of apocrine DCIS, GCDFP-15 positivity was detected in seven (77.8%), while five (55.6%) and six (66.7%) cases were positive for GCDFP-24 and GCDFP-44, respectively. CONCLUSIONS: The results indicate that there is no significant association between the expression of the studied proteins and the degree of differentiation of DCIS of the breast. Moreover, some morphologically apocrine DCIS cases appear to lose expression of these proteins.     

Apocrine carcinoma of the breast. A morphologic and immunocytochemical study.

The mode of recognition and hence the frequency of apocrine differentiation in breast carcinomas, assessed on purely morphologic grounds, remains uncertain. One hundred consecutive cases of breast carcinoma were studied in order to establish the incidence of this type of tumor. With the use of an immunocytochemical method for the detection of GCDFP-15, a protein present in apocrine epithelium and in the fluid of tension cyst of the breast, the presence of apocrine differentiation was confirmed in 4 cases initially diagnosed as apocrine carcinomas on histologic grounds. Eight additional cases contained immunoreactive cells: 1 contained 10% of positive cells scattered throughout the tumor, and the other 7 cases were only focally positive. In 4 of these latter cases positive staining was confined to the in situ component. The ultrastructural findings in 2 cases of apocrine carcinoma are discussed in order to link the morphologic features for recognizing this tumor type and the presence of the antigenic apocrine marker.     

Cell-type- and tumour-type-related patterns of bcl-2 reactivity in mesenchymal cells and soft tissue tumours

 GCDFP-15, a glycoprotein identified in the cyst fluid of cystic breast disease, is considered to be a marker of apocrine differentiation. Studies on GCDFP-15 localization in adult normal tissues are lacking, and no information on GCDFP-15 expression during fetal development has been reported. We investigated GCDFP-15 expression in a large series of formalin-fixed, paraffin-embedded normal human adult and fetal tissues using the monoclonal antibody BRST-2. In normal adult tissues GCDFP-15 expression was found in all apocrine, lacrimal, ceruminous and Moll’s glands and in numerous serous cells of the submandibular, sublingual and minor salivary glands. The serous cells of nasal and bronchial glands were also positive; parotid and laryngeal glands showed rare immunoreactive cells. GCDFP-15-positive cells were observed in all cutaneous eccrine glands from different body sites. In fetal tissues immunoreactivity was observed in numerous acinous cells of all tracheal, bronchial and submandibular salivary glands. GCDFP-15 positivity was identified in numerous cells of all axillary sweat glands and in rare cells of some sweat glands of the thorax, abdomen, back, leg and arm. In both apocrine and nonapocrine glands GCDFP-15 was always localized in the secretory component. These data suggest that GCDFP-15 is a glandular differentiation marker associated with apocrine secretion; that it is expressed in glands that have phylogenetic origins in common with apocrine glands (submandibular salivary and submucosal bronchial glands); and that eccrine cutaneous glands express GCDFP-15 and thus might be referred to as mixed apocrine-eccrine glands. GCDFP-15 is expressed during fetal development and may represent a common marker of embryologically linked glandular structures. Received: 22 May 1997 / Accepted: 15 September 1997     

PIP/GCDFP-15 gene expression and apocrine differentiation in carcinomas of the breast

The frequency and the significance of apocrine differentiation in carcinomas of the breast are uncertain, because of the lack of reliable and reproducible criteria for morphological diagnosis. The 15 kDa glycoprotein of cystic breast disease (GCDFP-15) is regarded as a specific functional marker of apocrine cells. Expression of the prolactin-inducible protein (PIP)/GCDFP-15 gene was investigated by Northern blot analysis and in situ hybridization in breast cancer cell lines and in an unselected series (33 cases) of primary carcinomas of the breast. On the same cases, histological assessment of apocrine differentiation and immunocytochemical detection of GCDFP-15 were also performed and correlated with follow-up data. The presence of PIP/GCDFP-15 mRNA was a feature of a relatively high number of cases, but was incompletely correlated with histological and immunocytochemical evidences of apocrine differentiation. Expression of the PIP/GCDFP-15 gene was significantly associated with relapse-free survival, and may represent a novel variable of functional and prognostic relevance.Work supported by grants from Associazione Italiana per la Ricerca ca sul Cancro (AIRC) (Milan, Italy), Consiglio Nazionale Ricerche (CNR, grant N. 93.02125.PF39), Ministero dell' Universita' e della Ricerca Scientifica e Tecnologica (MURST), Rome, Italy.     

Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women.

Neuroendocrine (NE) breast carcinomas are a rare entity in young women; however, their frequency increases in aged patients. The present work demonstrates that NE breast carcinomas in elderly women can also express an apocrine immunophenotype and analyzes the histological and clinical aspects of such differentiation. A selected series of 50 NE tumors (positive for NE markers in >/=50% of the cells) was tested for the immunocytochemical expression of gross cystic disease fluid protein-15 (GCDFP-15). The results demonstrated that about 50% of moderately (G2) and well-differentiated (G1) NE breast carcinomas (mucinous, solid papillary, and solid cohesive histotypes) coexpressed the apocrine marker. In these cases, specific mRNA for GCDFP-15 (PIP) and for chromogranin A (ChA) was demonstrated using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and poorly differentiated carcinomas (G3), including one case of atypical carcinoid, were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor status of these lesions was evaluated to test a possible involvement of androgen receptors in apocrine differentiation. We demonstrated that the level of AR and the mean age of patients at diagnosis were significantly higher in apocrine than in nonapocrine differentiated tumors. The histological grade and the expression of estrogen receptor (ER) significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated. The most original result of our study is therefore the demonstration of a possible divergent apocrine differentiation of NE breast carcinomas that might be regulated by the activation of androgen receptors in elder patients. In addition, the possibility for using Chs or GCDFP-15 serum values in the follow-up of these patients, as demonstrated in two cases of the present series, can justify the immunophenotyping of the tumors.     

The enigmatic nature of apocrine breast lesions

Epithelial cells of fetal breast glandular structures, at the third trimester of pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than a result of metaplasia, and it has been demonstrated that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but androgen-receptor (AR) positive. The significance of AR expression in apocrine epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast entities, ranging from benign lesions to invasive carcinoma. Breast cancer accounts 32% of all cancer cases among women and is the most common type of cancer in women. Little is known about breast carcinogenesis. Widely, it is accepted that breast cancer, like most other type of cancer, is being developed through the accumulation of genetic aberrations. Apocrine epithelium may reflect instability of the breast epithelium, creating an environment favouring further oncogenic alterations. In the last decade, several lines of evidence support the idea that some breast benign epithelial apocrine lesions are clonal lesions and may be considered as truly pre-malignant or precursors of breast carcinoma. Apocrine changes in many cases do not present any diagnostic difficulty; on the other hand, apocrine proliferations with cytologic atypia can be particularly difficult and challenging. The purpose of this study is to collect and highlight the areas of consensus in the literature as well as the controversial areas concerning the apocrine epithelium of the breast.     

Gross cystic disease fluid protein-15 in salivary gland tumors

Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms. Benign tumors (76% reactive) were more often labeled than malignant lesions (28% reactive) by this antibody; overall, 53 (41%) of 133 cases were positive for GCDFP-15. Notably, the tubuloglandular components in 17 (81%) of 21 pleomorphic adenomas were reactive, but no example of either adenoid cystic carcinoma or polymorphous low-grade adenocarcinoma were labeled. In contrast, 24% of adenocarcinomas stained with this antibody. The apparent expression of GCDFP-15 by a spectrum of salivary gland tumors supports their biologic relationship to lesions of the cutaneous apocrine glands and breast. Furthermore, the demonstration of this determinant may be of use in suggesting the salivary gland nature of poorly differentiated carcinomas of the head and neck, and it may facilitate the separation of pleomorphic adenoma from histologically similar malignant neoplasms in the salivary glands themselves.     

Signet Ring Cells in Breast Carcinoma

Two cases of breast carcinoma composed predominantly of neoplastic cells with a signet ring appearance, one a case of invasive lobular carcinoma (ILC) and the other a case of invasive ductal carcinoma (IDC), were examined electron microscopically and immunohistochemically. In signet ring cells in the ILC, mucin was demonstrated ultrastructur-ally in the intracytoplasmic lumina and also to a small degree in the cytoplasmic mucous granules, whereas in signet ring cells in the IDC, mucin was found only in the cytoplasmic mucous granules. Immunohistochemically, signet ring cells in the ILC were intensely positive for gross cystic disease fluid protein (GCDFP-15), but those in the IDC showed no immunoreaction for GCDFP-15. Thus ultrastructural features and GCDFP 15 immunoreactivity appear to be useful for distinguishing between the two different types of signet ring cells.     

Histiocytoid breast carcinoma: Histological, immunohistochemical, ultrastructural, cytological and clinicopathological studies

Histiocytoid breast carcinoma (HBC) is a rare variant of breast carcinoma and often causes a diagnostic dilemma because of its histological similarities to some types of breast cancer and benign lesions. To elucidate the incidence of HBC and its biological properties, histological specimens from 1010 breast cancer patients treated at Yokohama Minami Kyosai Hospital between 1972 and 1996 were reviewed. Three cases of pure HBC and three cases of combined HBC (two with pleomorphlc lobular carcinoma and one with apocrine ductal carcinoma) were found, yielding an Incidence of 0.3% for each. Two of the three pure HBC cases contained foci of in situ lobular carcinoma. Targetoid and Indian file invasive patterns, the features characteristic of lobular carcinoma, were present in all three pure HBC cases and in two of the three combined HBC with pleomorphic lobular carcinoma. These results, together with those of previous studies, suggested that the majority of HBC are of lobular origin, although the apocrine ductai origin is also possible in a small number of HBC. Diastase-resistant periodic add-Schiff-positive granules and granular immunoreactivities for gross cystic disease fluid protein-15 (GCDFP-15) were characteristic of the histiocytoid tumor cells in both the pure and combined HBC, suggesting the apocrine differentiation of tumor cells. All three pure HBC cases were in stage 1 and were free of the disease for up to 5 years and 1 month after the lumpectomy. Thus, the prognosis of HBC appears to be dependent on the stage of the disease and may not always be poor, as indicated by the original report mentioning a preferential eyelid metastasis.     

Bilateral apocrine carcinoma of the breast Molecular and immunocytochemical evidence for two independent primary tumours

Apocrine carcinoma is an uncommon variant of breast cancer. The frequency of bilaterality in patients who have apocrine carcinoma in one breast is not significantly different from that for bilateral mammary carcinomas in general, but bilateral apocrine carcinomas are very uncommon. We report on a bilateral apocrine carcinoma of the breast in a 74-year-old woman. The apocrine differentiation in both tumours was confirmed by the positivity of the cytoplasmic granules for PAS after diastase digestion and immunoreactivity for GCDFP-15 and sialyl-Tn. The tumour in the right breast showed immunohistochemical expression of p53, and a mutation was demonstrated by PCR-SSCP; the tumour in the left breast was negative for p53 on immunohistochemistry, and no mutation was found at the molecular level. c-erbB2 expression was not detected in the right tumour but there was overexpression (at the cell membrane) in the left tumour. Both tumours were aneuploid: the right tumour displayed multiple stemlines, whereas the left tumour had a triploid profile. Using the fluorescence in situ hybridization technique we demonstrated that both tumours displayed chromosome 17 polysomy and numerical abnormalities of chromosome 1, polysomy in the right and monosomy in the left tumour. We conclude that the two tumours are probably independent, as are most bilateral carcinomas of the breast.     

Monoclonal antibody B72.3 immunostaining of breast carcinoma. Patterns of staining and relationship to mucin content and GCDFP-15 reactivity.

Around 80% of breast carcinomas express the tumor-associated glycoprotein-72, as demonstrated by positive immunostaining with the monoclonal antibody B72.3. We have investigated the pattern of B72.3 immunostaining in 88 breast carcinomas of different types, with the use of an immunoperoxidase technique. As tumor-associated glycoprotein-72 has mucinlike properties and is usually present in cells that show apocrine differentiation, we have also compared the results of B72.3 immunostaining in these tumors with the staining results for mucin and GCDFP-15, which is another antibody that recognizes apocrine differentiation. A variable degree of B72.3 immunostaining was seen in 60 cases (68%). The staining patterns varied with the histological type and sometimes within the same type. A significant relationship was demonstrated between B72.3 positivity and the presence of acidic mucin in the tumors, but not with their staining for GCDFP-15. The extent, distribution, and pattern of immunostaining for B72.3 varies in different types of breast carcinoma; this fact has to be taken into consideration if radiolabeled B72.3 monoclonal antibodies are going to be used for therapeutic purposes.     

Value of gross cystic disease fluid protein-15 in distinguishing metastatic breast carcinomas among poorly differentiated neoplasms involving the ovary

Women with breast cancer have an increased risk of developing primary ovarian tumors. Because a differential diagnosis between primary and metastatic tumors may be difficult in poorly differentiated ovarian neoplasms, breast carcinoma markers may be helpful in establishing the primary site of origin. Gross cystic disease fluid protein-15 (GCDFP-15), a well-known marker of apocrine differentiation, has been reported as a highly specific and sensitive breast carcinoma marker. To evaluate the usefulness of GCDFP-15 as a marker for metastatic breast cancer, we have studied, by the avidin-biotin-peroxidase technique, 14 cases of breast cancer metastatic to the ovary and compared them with 32 primary ovarian tumors and seven cases of ovarian metastases other than breast in origin. Two cases of primary ovarian cancer metastatic to the breast were also included. A strong cytoplasmic immunostaining was found in 10 of 14 cases (71%) of ovarian metastasis from breast carcinoma, and in most cases a characteristic paranuclear staining was noted. All primary ovarian tumors were negative. Ovarian metastases from tumors other than breast and both cases of ovarian carcinoma metastatic to the breast were negative. These results are highly significant (P less than .00001) and demonstrate the value of GCDFP-15 in establishing a primary breast origin among neoplasms of unknown origin involving the ovaries.     

Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin

The identification of metastatic carcinoma of the breast may be difficult in the absence of a previous history of breast cancer. Various immunophenotypic markers have been introduced to aid in this process. A monoclonal antibody directed at a 15-kilodalton (kd) gross cystic disease fluid protein (GCDFP-15) was applied immunohistochemically to paraffin sections of 105 breast cancers and 585 nonmammary malignancies in order to assess its value in this context. In addition, GCDFP-15 was compared with another putative mammary epithelial marker, alpha-lactalbumin (ALA), with respect to sensitivity and specificity for a diagnosis of breast carcinoma. Overall, the rates of specificity and sensitivity and the predictive value of a positive result for GCDFP-15 were 95%, 74%, and 74%, respectively. Corresponding statistical parameters for ALA were 50%, 50%, and 23%. A consistent congruency between the reactivity patterns of primary and metastatic breast cancers was noted for GCDFP-15 but not for ALA. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were carcinomas of the salivary glands, sweat glands, and prostate. Since the latter three types of lesions are unlikely to be diagnosed as metastatic breast cancer, statistical indices were recalculated after exclusion of these three tumor types. Following this exclusion, the adjusted rate of specificity of GCDFP-15 and the predictive value of a positive result for a diagnosis of metastatic carcinoma of the breast were each 99%. In contrast, predictive parameters for ALA were not altered. These results show that GCDFP-15 is a specific marker for breast cancer and is superior to ALA in this respect.     

Regulation of GCDFP-15 expression in human mammary cancer cells.

Gross cystic disease fluid protein 15 (GCDFP-15) is a major protein component of benign breast gross cysts. It is also found in approximately 50% of all breast cancer specimens. Androgen receptor (AR) mediated regulation of GCDFP-15 expression was investigated in the AR-positive human mammary cancer cell lines MFM-223 and ZR-75-1. Proliferation of MFM-223 and ZR-75-1 cells is inhibited by androgens. Ten nM 5alpha-dihydrotestosterone stimulated the expression of GCDFP-15 mRNA in MFM-223 (ca. 3-fold) and ZR-75-1 cancer cells (ca. 30-fold) as well as the secretion of GCDFP-15 into the culture medium. Competition experiments with DHT and the antiandrogens hydroxyflutamide and casodex confirmed the involvement of the AR in the regulation of GCDFP-15. Both antiandrogens inhibited GCDFP-15 mRNA expression even in the absence of DHT. AR mRNA was down-regulated in MFM-223 and ZR-75-1 cells (80 and 20% of the control, respectively) during incubation with DHT. Our data demonstrate the effective inhibition of GCDFP-15 expression by pure antiandrogens.     

An immunohistochemical study of the tissue distribution of the breast cyst fluid protein, zinc alpha2 glycoprotein

Zinc alpha 2 glycoprotein is one of the proteins present in breast cyst fluids, being found at levels 30-50 times its plasma concentration. Using an immunoperoxidase technique the distribution of this glycoprotein has been studied in a range of non-mammary tissues and carcinomas, as well as in normal, benign and malignant breast specimens. The breast cyst fluid protein was detected in all apocrine cells of skin and in the apocrine metaplastic epithelium lining of breast cysts. A progression was apparent from normal to hyperplastic breast in the number of cells reacting, particularly of cystically dilated acini, to a final consistent staining of apocrine-lined cysts. Zinc alpha 2 glycoprotein was demonstrated in 16 of 33 invasive carcinomas, 15 of which were eosinophilic on haematoxylin and eosin staining, and in one of three non-invasive carcinomas. No staining was apparent in other non-mammary tissues and carcinomas apart from weak reactivity of serous cells of the parotid gland. Zinc alpha 2 glycoprotein is, therefore, a reliable immunohistochemical marker of apocrine cell differentiation.     

Mammaglobin vs GCDFP-15: an immunohistologic validation survey for sensitivity and specificity

There are limited data that compare the usefulness of mammaglobin with gross cystic disease fluid protein-15 (GCDFP-15) in the identification of breast carcinomas. Whole tissue sections of 29 breast carcinomas with matched lymph node metastases and 63 breast carcinomas on tissue microarray were stained with mammaglobin cocktail and GCDFP-15 antibodies. In addition, tissue microarrays (US Biomax, Rockville, MD) containing 544 different human tumors were also stained with the mammaglobin antibody cocktail. Positive staining was seen in 67 (55.4%) of 121 breast carcinomas with mammaglobin and in 28 cases (23.1%) with GCDFP-15. In the majority of cases, the staining intensity and number of cells staining were higher with mammaglobin than with GCDFP-15. Positive mammaglobin staining was also seen in 44 (8.1%) of 544 nonbreast tumors. Mammaglobin is a more sensitive marker than GCDFP-15 for breast carcinoma; however, it lacks the specificity of GCDFP-15.