Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: its correlation to histologic findings in 43 cases.
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We examined Ki-67, p53, p21, and p27 immunolocalization in 43 cases of apocrine lesions of the breast and correlated these findings with histologic parameters to understand their biologic significance. Twenty cases were benign, 1 case was borderline, and 22 cases were diagnosed as malignant, including 9 intraductal and 13 invasive apocrine carcinomas. Both the ratio of Ki-67-positive cases (17 of 21 [88.9%] versus 1 of 19 [5.3%]; P < .001) and the Ki-67 labeling index of positive cases examined (15.0% versus 2.7%; P < .005) were significantly higher in malignant than in benign apocrine lesions. None of the benign or borderline cases was immunohistochemically positive for p53, but 15 of 22 malignant cases (68.2%) demonstrated p53 (P < .001). In addition, the ratio of p53-positive cases was significantly higher in high nuclear grade cases (11 of 13 [84.6%]) than in intermediate nuclear grade cases (4 of 9 [44.4%]; P < .05). P53 immunoreactivity was also positively correlated with the nuclear grade of carcinoma cases examined in this study. Neither p21 nor p27 demonstrated any correlation with histologic parameters or findings of the apocrine lesions. Results of these studies suggest that Ki-67 and p53 may be good markers for differentiation between benign and malignant breast apocrine lesions. (+info)
Immunohistochemical localisation of androgen receptor in apocrine metaplasia and apocrine adenosis of the breast: relation to oestrogen and progesterone receptors.
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AIM: To investigate the receptor status of the sex steroid hormones in apocrine metaplasia of the breast. METHODS: 82 cases of apocrine metaplasia, including 18 of the rare lesion apocrine adenosis, were studied immunohistochemically for the expression of androgen receptor, oestrogen receptor, and progesterone receptor proteins on formalin fixed, paraffin embedded tissue sections. The standard avidin biotin complex (ABC) technique was followed and appropriate positive and negative controls were used. RESULTS: All the studied cases (82/82) were positive for androgen receptor, but were negative for oestrogen receptor and progesterone receptor. CONCLUSIONS: Apocrine metaplastic epithelium, unlike the normal breast epithelium, is responsive to androgens, through androgen receptors, rather than to the female sex hormones. This may have clinical implications. (+info)
A novel aspartyl proteinase from apocrine epithelia and breast tumors.
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GCDFP-15 (gross cystic disease fluid protein, 15 kDa) is a secretory marker of apocrine differentiation in breast carcinoma. In human breast cancer cell lines, gene expression is regulated by hormones, including androgens and prolactin. The protein is also known under different names in different body fluids such as gp17 in seminal plasma. GCDFP-15/gp17 is a ligand of CD4 and is a potent inhibitor of T-cell apoptosis induced by sequential CD4/T-cell receptor triggering. We now report that GCDFP-15/gp17 is a protease exhibiting structural properties relating it to the aspartyl proteinase superfamily. Unexpectedly, GCDFP-15/gp17 appears to be related to the retroviral members rather than to the known cellular members of this class. Site-specific mutagenesis of Asp(22) (predicted to be catalytically important for the active site) and pepstatin A inhibition confirmed that the protein is an aspartic-type protease. We also show that, among the substrates tested, GCDFP-15/gp17 is specific for fibronectin. The study of GCDFP-15/gp17-mediated proteolysis may provide a handle to understand phenomena as diverse as mammary tumor progression and fertilization. (+info)
Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor.
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Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease. (+info)
Histo-physiology of the scent-marking glands of the penile pad, anal pouch, and the forefoot in the aardwolf (Proteles cristatus).
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The scentmarking glands of the anal pouch, penile pad, and the forefoot of the aardwolf (Proteles cristatus) were studied by histological, histochemical, immunohistochemical methods, and by electron microscopy. The morphological observations are correlated with eco-ethological aspects of this nocturnal animal. In all studied regions there was a superficial layer of holocrine sebaceous glands and a deeper layer of apocrine scent glands; these two types of glands apparently function in concert. Only in the forefoot were additional tubular glands, resembling eccrine sweat glands found, which may improve the frictional capacities of the paw, while apocrine and holocrine glands serve scent-marking functions of the forefoot. Penile pad and anal pouch are exclusively scent marking organs. The secretion modus of the apocrine glands is both via exocytosis and apocrine mechanism. Homogeneous apical, secretory granules, which contain glycoproteinaceous material, represent evidence for exocytosis. In the anal pouch, additional variably sized granules contain endogenous pigments which are probably responsible for the brownish coloration of the secretory product of the male animals. Variable heights of the glandular cells, frequent apical tall protrusions as well as pinched-off pieces of cytoplasm in the glandular tubules support the concept of an apocrine secretion in the scent glands. The immunohistochemical staining pattern of actin points to the involvement of actin filaments in the pinching-off process of the apical cell protrusion, which does not contain any cell organelles. The variable actin staining patterns suggest a dynamic process during which actin filaments form a ring or sheet at the basis of the pinching-off bleb. Proliferative and apoptotic phenomena show no preference for active and inactive glandular cells suggesting that replacement of cells occurs independently of the functional status of the glands. (+info)
Aspects of general antimicrobial properties of skin secretions in the common seal Phoca vitulina.
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Considerable amounts of several saccharide residues (alpha-D-Man, beta-D-GlcNAc, alpha-D-GalNAc, beta-D-Gal, alpha-D-Gal, alpha-L-Fuc, NeuNAc) are demonstrated by lectin histochemistry in the sections of the sebaceous glands, and, particularly, the apocrine tubular glands of the common seal. These sugars may be liberated on the skin surface by microbial activities and, then, represent a general antimicrobial protection mechanism of the skin because of their ability to inhibit the adherence of different bacteria and fungi to the epidermis. (+info)
Molecular cytogenetic comparison of apocrine hyperplasia and apocrine carcinoma of the breast.
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The relationship of apocrine metaplasia to invasive breast cancer is controversial. Different authors have reported that apocrine differentiation in proliferative lesions may be a risk factor, a precursor lesion, or have no association with malignancy. The aim of this study was to compare the genetic alterations in benign apocrine hyperplasia with apocrine ductal carcinoma in situ (DCIS) and invasive apocrine carcinomas of the breast using comparative genomic hybridization. The mean number of alterations in apocrine hyperplasia was 4.1 (n = 10) compared to 10.2 in apocrine DCIS (n = 10) and 14.8 (n = 4) in invasive carcinoma. The most common alterations in apocrine hyperplasia were gains of 2q, 13q, and 1p and losses of 1p, 17q, 22q, 2p, 10q, and 16q. Apocrine DCIS and invasive carcinomas showed gains of 1q, 2q, 1p, and losses of 1p, 22q, 17q, 12q, and 16q as their most common DNA copy number changes. Apocrine hyperplasia is considered to be a benign lesion and its relationship to invasive carcinoma remains unclear. Our data suggest that some apocrine hyperplasias may be clonal proliferations. The mean number of alterations are lower in apocrine hyperplasia, however the changes show considerable overlap with those identified in in situ and invasive apocrine carcinoma. These alterations are also commonly seen in nonapocrine breast cancer. The data are consistent with apocrine hyperplasia as a putative nonobligate precursor of apocrine carcinoma. (+info)
Mixed apocrine/endocrine ductal carcinoma in situ of the breast coexistent with lobular carcinoma in situ.
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An unusual mixed form of ductal carcinoma in situ (DCIS) of the breast is described, which exhibits a biphenotypic morphology encompassing a range of differential diagnostic DCIS subtypes. In addition, immunophenotypic and ultrastructural studies demonstrate neuroendocrine and apocrine differentiation, raising questions regarding appropriate classification and biological behaviour. In two cases, coexistence of this mixed form of DCIS with lobular carcinoma in situ (LCIS) in the same duct lobular units is an additional unusual feature that might, at least in some cases, indicate a closer relation between them. (+info)