Cell turnover in apocrine metaplasia of the human mammary gland epithelium: apoptosis, proliferation, and immunohistochemical detection of Bcl-2, Bax, EGFR, and c-erbB2 gene products

Feuerhake, Friedrich; Unterberger, Pia; Höfter, Eugen

doi:10.1078/0065-1281-00578

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…In the current study, we classified APM according to criteria previously defined by Page et al (3) in an attempt to define whether classifying APM would help towards a further understanding of their nature. A number of studies have attempted to investigate the proliferative capacity of APM, however, no attempts were made to stratify APM according to histological criteria (23,32,(44)(45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Alterations of the Cell Cycle Regulators Cyclin D1, Cyclin A, p27, p21, p16, and pRb in Apocrine Metaplasia of the Breast

Elayat¹,

Selim²,

Wells³

2009

The Breast Journal

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G1/S transition defects have been a proposed requirement for tumor development. Apocrine metaplasia (APM) in the breast has been held as a sign of benignity. Yet, a number of studies have reported the presence of molecular abnormalities in some forms of APM suggesting a possible oncogenic potential for some of these lesions. We currently investigate the role of some of the cell cycle proteins, previously reported to be de-regulated in breast cancer, in an attempt to assess their significance in APM. Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki-67 was examined in 93 cases of APM. The cases were divided into nonpapillary (NAPM) (30 cases) and papillary metaplasia (PAPM) (63 cases). PAPM was further subdivided into simple papillary (SPAPM) (29 cases), complex papillary (28 cases) and highly complex papillary (six cases). For statistical analysis, the last two groups were merged together (CPAPM). The results showed that increased histological complexity was associated with significant increase of proliferative capacity and alterations of the cell cycle control. The median Ki-67 index was 1.5% in SPAPM and 4.8% in the CPAPM. Also, alterations of the cell cycle regulators were significantly higher in the CPAPM than in the SPAPM. NAPM was generally similar to normal breast epithelium. Apocrine cells were negative for p16 while pRb was expressed in all cases. These findings suggest that in complex forms of APM, there is a considerable degree of cellular unrest. This may contribute to increased susceptibility to carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Alterations of the Cell Cycle Regulators Cyclin D1, Cyclin A, p27, p21, p16, and pRb in Apocrine Metaplasia of the Breast

Elayat¹,

Selim²,

Wells³

2009

The Breast Journal

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“…It may be also a misleading feature. [36][37][38][39][40] It has been suggested that bcl-2 is expressed in benign breast tissues that retain a proliferative capacity and partial differentiation, 40 but the exact reason for bcl-2 negativity in apocrine metaplastic epithelium is not known. [31][32][33][34] Moreover, a recent study employing a clonality analysis using a PCR-based method for females heterozygous for a BstXI polymorphism of the X-linked phosphoglycerokinase gene revealed the monoclonal nature of a case of apocrine adenosis.…”

Section: Discussionmentioning

confidence: 99%

Hidradenoma Papilliferum with Oxyphilic Metaplasia

Kazakov

Mikysková²,

Kutzner³

et al. 2005

The American Journal of Dermatopathology

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Reported here are 18 cases of hidradenoma papilliferum with oxyphilic metaplasia. All patients were women ranging in age from 29 to 74 years. Each presented clinically with a small, solitary tumor in the anogenital region. Microscopically, in addition to classic histopathological features, in every case there was oxyphilic metaplasia of the constituent epithelial cells. This finding could be likened to apocrine metaplasia, a term used in breast pathology. Other histopathological findings observed in this series, analogous to benign breast disease, included sclerosing adenosis-like changes, atypical apocrine adenosis-like changes, changes corresponding to usual ductal epithelial hyperplasia, epitheliomatosis with a streaming growth pattern, lamprocyte-like changes, clear cell change of the myoepithelium, foamy histiocyte reaction, and stromal fibrosis. Immunohistochemistry inferred that in the majority of cases oxyphilic metaplasia resulted from more lysosomes, whereas numerous mitochondria were detected in only 3 cases. Using 2 different PCR methods we identified HPV in 4 of 15 cases of hidradenoma with oxyphilic metaplasia. In addition, HPV was detected in 3 of 16 conventional papillary hidradenomas used as a control group. The following HPV types were identified: 16, 31, 33, 53, and 56. The last type was found in 5 cases. More than one HPV type from a single lesion was seen in 5 cases. Our observations are consistent with previous publications noting similarities between tumors of the breast and sweat glands. Oxyphilic metaplasia, areas with solid growth, and changes simulating atypical apocrine adenosis are rare and poorly recognized in hidradenoma papilliferum and may cause diagnostic difficulties; in our cases several submitting pathologists suspected malignancy. A causal role for HPV in hidradenoma papilliferum cannot be confirmed from our results, as the detection rate is too low. The exact role of the HPV in etiology and pathogenesis of this neoplasm has yet to be determined.

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“…The mechanism of development of apocrine differentiation has not been identified. Furthermore, its relation with particular subtypes of mammary carcinoma has not been elucidated to date 17. and the relation between apocrine metaplasia and invasive breast carcinoma remains a matter of controversy 18.…”

Section: Discussionmentioning

confidence: 99%

Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopy

Loibl

Minckwitz

Weber

et al. 2002

Cancer

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BACKGROUND Nitric oxide (NO) is present in various human solid tumors and tumor cell lines, and it is believed that NO plays an important role in tumor growth. An increased NO concentration catalyzed by NO synthase (NOS) is cytotoxic and can promote apoptosis. The expression of endothelial NOS (e‐NOS) and induced NOS (i‐NOS) was examined in various breast tumors. METHODS Immunohistochemical staining with a monoclonal antibody (Ab) against e‐NOS and a polyclonal Ab against i‐NOS was performed on paraffin embedded tissues from 41 benign breast lesions, 9 in situ breast lesions, and 54 invasive breast lesions. Functionality was confirmed by detection of NO using spin‐trapping electron paramagnetic resonance (EPR) spectroscopy. RESULTS e‐NOS expression was found in 2 benign lesions (5%; 1 fibroadenoma and 1 proliferative mastopathy), in 5 in situ lesions (56%), and in 33 invasive lesions (61%). None of the benign lesions was positive for i‐NOS, but 6 in situ lesions (67%) and 33 invasive lesions (61%) showed tumor cell staining. In particular, capillaries that were embedded in lymphocytic stroma showed a positive reaction for e‐NOS. The functionality of NOS was demonstrated by direct NO formation using the EPR spin‐trapping method. Tumors that were positive for e‐NOS were observed more often in younger patients (P = 0.05). These tumors more frequently were highly differentiated or moderately differentiated and more often showed invasive ductal subtypes and a lower proliferation rate. Tumors that were positive for both e‐NOS and i‐NOS were more likely to be lymph node negative tumors. Both i‐NOS‐expressing lesions and e‐NOS‐expressing lesions showed strong coexpression (P = 0.00001). CONCLUSIONS NOS is detected predominantly in in situ lesions and invasive breast lesions but rarely in benign lesions. NOS is found more frequently in invasive carcinomas with low malignancy. Using the spin‐trapping EPR method, this study demonstrates direct NO formation in human breast tumors for the first time. Cancer 2002;95:1191–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10817

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Cell turnover in apocrine metaplasia of the human mammary gland epithelium: apoptosis, proliferation, and immunohistochemical detection of Bcl-2, Bax, EGFR, and c-erbB2 gene products

Cited by 4 publications

References 31 publications

Alterations of the Cell Cycle Regulators Cyclin D1, Cyclin A, p27, p21, p16, and pRb in Apocrine Metaplasia of the Breast

Alterations of the Cell Cycle Regulators Cyclin D1, Cyclin A, p27, p21, p16, and pRb in Apocrine Metaplasia of the Breast

Hidradenoma Papilliferum with Oxyphilic Metaplasia

Expression of endothelial and inducible nitric oxide synthase in benign and malignant lesions of the breast and measurement of nitric oxide using electron paramagnetic resonance spectroscopy

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