Molecular cytogenetic comparison of apocrine hyperplasia and apocrine carcinoma of the breast.

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.

[1]  W. Miller,et al.  Risk of breast cancer in women with palpable breast cysts: a prospective study , 1999, The Lancet.

[2]  W. Dupont,et al.  Ductal carcinoma in situ of the breast with apocrine cytology: definition of a borderline category. , 1994, Human Pathology.

[3]  M. J. van de Vijver,et al.  Ductal carcinoma in situ: a proposal for a new classification. , 1994, Seminars in diagnostic pathology.

[4]  J. Hamerton,et al.  The gene for prolactin-inducible protein (PIP), uniquely expressed in exocrine organs, maps to chromosome 7 , 1989, Somatic cell and molecular genetics.

[5]  S. Hsu,et al.  Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. , 1981, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[6]  G. Bevilacqua,et al.  Apocrine epithelium of the breast: does it result from metaplasia? , 1997, Virchows Archiv.

[7]  D. Haagensen.  Is Cystic Disease Related to Breast Cancer? , 1991, The American journal of surgical pathology.

[8]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. , 1999, Critical reviews in oncology/hematology.

[9]  P. Bruzzi,et al.  Cohort study of association of risk of breast cancer with cyst type in women with gross cystic disease of the breast , 1997, BMJ.

[10]  S. Wells,et al.  Breast gross cystic disease fluid analysis. I. Isolation and radioimmunoassay for a major component protein. , 1979, Journal of the National Cancer Institute.

[11]  T. Manabe,et al.  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 , 2000, Modern Pathology.

[12]  J. Töth,et al.  Significance of Apocrine Metaplasia in Mammary Carcinogenesis , 1990, Annals of the New York Academy of Sciences.

[13]  J. Delhanty,et al.  Detailed chromosomal and molecular genetic analysis of single cells by whole genome amplification and comparative genomic hybridisation. , 1999, Nucleic acids research.

[14]  Eusebi,et al.  Long-term follow-up of in situ carcinoma of the breast. , 1994, Seminars in diagnostic pathology.

[15]  P. Rosen.  Rosen's Breast Pathology , 2001 .

[16]  M. Stratton,et al.  Detection of allelic imbalance indicates that a proportion of mammary hyperplasia of usual type are clonal, neoplastic proliferations. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[17]  M. Costantini,et al.  Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast. , 1992, Cancer research.

[18]  A. Selim,et al.  Immunohistochemical localisation of androgen receptor in apocrine metaplasia and apocrine adenosis of the breast: relation to oestrogen and progesterone receptors. , 1999, Journal of clinical pathology.

[19]  D. Page,et al.  Relation between component parts of fibrocystic disease complex and breast cancer. , 1978, Journal of the National Cancer Institute.

[20]  Ali Ahmed.  Apocrine metaplasia in cystic hyperplastic mastopathy Histochemical and ultrastructural observations , 1975, The Journal of pathology.

[21]  C. Bodian,et al.  Breast Carcinoma: Risk and Detection , 1981 .

[22]  J. Davies,et al.  Apocrine adenosis: a precursor of aggressive breast cancer? , 1995, Journal of clinical pathology.

[23]  H M Jensen,et al.  An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. , 1975, Journal of the National Cancer Institute.

[24]  C. Alpers,et al.  Apocrine cystic metaplasia: subgross pathology and prevalence in cancer-associated versus random autopsy breasts. , 1987, Human pathology.

[25]  W. Dupont,et al.  Papillary apocrine change of the breast: associations with atypical hyperplasia and risk of breast cancer. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[26]  C. Poremba,et al.  Comparative genomic hybridization of ductal carcinoma in situ of the breast—evidence of multiple genetic pathways , 1999, The Journal of pathology.

[27]  D. Spandidos,et al.  Immunohistochemical study of ras and myc oncoproteins in apocrine breast lesions with and without papillomatosis. , 1992, European journal of gynaecological oncology.

[28]  V. Eusebi,et al.  Apocrine carcinoma of the breast. A morphologic and immunocytochemical study. , 1986, The American journal of pathology.

[29]  A. Yates,et al.  Apocrine carcinoma and apocrine metaplasia , 1988, Histopathology.

[30]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.

[31]  V. Eusebi,et al.  Apocrine Differentiation in Breast Epithelium , 1997 .

[32]  M. Emmert-Buck,et al.  Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomas of the breast. , 1999, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[33]  F. W. Foote,et al.  Comparative Studies of Cancerous Versus Noncancerous Breasts. , 1945, Annals of surgery.