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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This issue of The Breast includes an elegant study by Selim et al. on c-myc gene amplification and protein overexpression in apocrine metaplasia (APM) and apocrine adenosis (AA) of the breast using paraffin-embedded tissue. In their report, the authors observe that all cases of APM and AA harbored c-myc protein overexpression, but no definitive gene amplification was found. Most importantly, they observed that the percentage of cells expressing c-myc in APM and AA was significantly correlated with cell proliferation, as assessed by Ki-67 immunolabeling index. On the basis of their findings and of previously reported studies, the authors suggest that c-myc overexpression occurs in early stages of breast carcinogenesis, that c-myc gene amplification may be a late event, and that in APM and AA c-myc overexpression is related to cell proliferation. Selim et al. findings have brought to our attention two thorny but rather important issues regarding current concepts of apocrine changes and their association with breast carcinomas, and also the role of c-myc in breast carcinogenesis.
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PMID:Oncogenes, granules and breast cancer: what has c-myc to do with apocrine changes? 1496 11

We performed a study on the expression of the PCPH protein in samples corresponding to normal, pre-malignant and malignant stages of the human mammary gland by using protocols of immunohistochemistry and Western blot analysis with anti-PCPH specific antibodies. Results obtained from the immunohistochemical study showed that PCPH was undetectable in samples of normal breast and of benign diseases, with the exception of glands presenting apocrine metaplasia, in which an intense PCPH stain was observed both in the basal cytoplasm of the secretory cells and in the apocrine secretion. On the contrary, an intense labeling was observed in the cytoplasm of neoplastic cells in samples of both ductal and lobular carcinoma in situ, with this immunostaining increasing even further in samples of infiltrating carcinoma, both ductal and lobular. Western blot analyses of the same set of samples detected a 47 kDa form as the main PCPH polypeptide present in all cases studied. However, whereas this 47 kDa polypeptide was the only PCPH form detected in normal and pre-malignant samples, multiple forms could be detected in carcinoma samples, indicating the presence of altered PCPH polypeptides at these disease stages. These results were in agreement with those from the immunohistochemical study and together indicated that PCPH protein expression represents a good molecular marker to follow the process of human breast carcinogenesis. Furthermore, these results suggested that characterization of the pattern and level of PCPH expression may be a useful tool for early identification of breast cancers.
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PMID:Deregulated expression of the PCPH proto-oncogene in human breast cancers. 1537 29

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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PMID:Alterations of the cell cycle regulators cyclin D1, cyclin A, p27, p21, p16, and pRb in apocrine metaplasia of the breast. 1962 19

The precancerous changes of mammary glands in 7,12-dimethylbenz(alpha)anthracene (DMBA) induced carcinogenesis in Wistar rats were examined. Carcinogen was inserted into the left fifth mammary gland of the anesthetised rats. After 35 days all the animals were sacrificed and mammary glands were extirpated. Macroscopic examination of mammary glands was performed and the tissue was processed for a pathohistological analysis. H&E, VanGieson's and Toluidine-blue methods were applied, as well as ABC immunohistochemical method with anti-cytokeratin antibodies.The identified precancerous changes resembled to aberrations of fibrocystic disease in women. The fibrosclerosis, lobular hyperplasia, cystic ductal dilatation and apocrine metaplasia of ductal epithelium were found. Micropapillomatoid hyperplasia was another frequent finding, but the presence of the real papilloma was not registered. The keratocysts with the squamous epithelial metaplasia were present in three of the animals. Dysplastic changes were found in the skin, above the treated glands. The difference in expression of cytokeratins, between normal and preneoplastic epithelium, makes cytokeratin useful for verification of early precancerous lesions. The epithelial ductus and ductulus cells of the mammary glands of animals belonging to the control group showed neither CK 19 nor CK 14 expression.
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PMID:Precancerous morphologic and functional aberrations in the rat mammary glands carcinogenesis. 1989 95

Aberrant methylation of promoter CpG islands is a hallmark of human cancers and is an early event in carcinogenesis. We examined whether promoter hypermethylation contributes to the pathogenesis of benign breast lesions along a progression continuum to invasive breast cancer. The exploratory study cohort comprised 17 breast cancer patients with multiple benign and/or in situ lesions concurrently present with invasive carcinoma within a tumor biopsy. DNA from tumor tissue, normal breast epithelium when present, benign lesions (fibroadenoma, hyperplasia, papilloma, sclerosing adenosis, apocrine metaplasia, atypical lobular hyperplasia or atypical ductal hyperplasia), and in situ lesions of lobular carcinoma and ductal carcinoma were interrogated for promoter methylation status in 22 tumor suppressor genes using the multiplex ligation-dependent probe amplification assay (MS-MLPA). Methylation specific PCR was performed to confirm hypermethylation detected by MS-MLPA. Promoter methylation was detected in 11/22 tumor suppressor genes in 16/17 cases. Hypermethylation of RASSF1 was most frequent, present in 14/17 cases, followed by APC in 12/17, and GSTP1 in 9/17 cases with establishment of an epigenetic monocloncal progression continuum to invasive breast cancer. Hypermethylated promoter regions in normal breast epithelium, benign, and premalignant lesions within the same tumor biopsy implicate RASSF1, APC, GSTP1, TIMP3, CDKN2B, CDKN2A, ESR1, CDH13, RARB, CASP8, and TP73 as early events. DNA hypermethylation underlies thepathogenesis of step-wise transformation along a monoclonal continuum from normal to preneoplasia to invasive breast cancer.
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PMID:Delineating an epigenetic continuum for initiation, transformation and progression to breast cancer. 2177 73