Expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast

Abstract

Molecular evidence has recently suggested a number of different pathways leading to the development of ductal carcinoma of the breast. The links between atypical ductal hyperplasia and low-grade ductal carcinoma in situ and lobular neoplasia and lobular carcinoma are well known pathologically, but high-grade in situ and invasive carcinomas appear to have a different biological oncogenetic pathway. Morphologically there is a similarity between apocrine cells and some cases of high-grade ductal carcinoma. In order to investigate this possibility a number of different biological markers known to occur in high-grade breast carcinomas were assessed in both apocrine metaplasia (APM) and a putative premalignant lesion called apocrine change within sclerosing adenosis (AA). In 64 cases of APM and 18 cases of AA we examined for expression of c-erbB2, p53, Bcl-2, Bax, c-myc and Ki-67 proteins using immunocytochemistry. c-erbB2 expression was seen in 55.6% of AA cases and in 10.9% of APM cases. p53 expression was detected in 27.8% of AA cases but only 1.6% of APM cases. All cases of AA and APM were negative for the anti-apoptotic protein Bcl-2, but all the APM and 33.3% of AA cases showed cytoplasmic positivity for Bax, a pro-apoptotic protein. All the cases of AA and APM were positive for c-myc oncoprotein, however, the mean percentage of nuclear positivity was 50% in AA and 37% in cases of APM cases. The mean percentage positivity for Ki-67, a proliferation associated antigen, was 3.6% in AA and 1.3% in APM. The results indicate that a subset of breast lesions containing APM epithelium show abnormal oncoprotein and apoptosis-related protein expression and have a higher proliferation rate.

Notch, Myc and Breast Cancer

“…In a large body of literature, the interpretation of IHC results obtained with the use of the mouse monoclonal antibody 9E10 (from various sources) against human MYC is not straightforward because the staining that is usually reported is cytoplasmic. Presumably, the cellular location of Myc immunostaining with 9E10 varies depending on fixation conditions 36 and some groups 37 (correctly, in our view) do not consider the detection of cytoplasmic signal as a positive result. On the other hand, exclusively nuclear staining, as expected, was reported 38 with the use of the mouse monoclonal 9E11 (various suppliers).…”

15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma

“…Additional immunophenotyping of the 21 carcinomas showed that with two exceptions (tumors 14 and 19), all were Bcl-2 and GATA-3 negative and several were p53 positive (Table III). There is compelling evidence indicating that benign apocrine proliferations are Bcl-2 negative (19,22); GATA-3 is a factor involved in luminal epithelial cell differentiation (46,47). Tumor 14 (15-PGDH/ACSM1 ϩ/Ϫ) contained cells that were GATA-3 positive and negative and it may correspond to a mix lesion.…”

“…Moreover some are positive for the gross cystic disease fluid protein-15 (GCDFP-15) (9, 24 -26), a marker that it is, however, not specific for these lesions (16,17,25). p53 expression has been observed in about 50% of invasive apocrine carcinomas (19,27), and there have been some reports addressing the characteristics of apocrine lesions using loss of heterozygosity (22,28,29) and comparative genome hybridization (10,30).…”

“…IACs have not been characterized at the molecular level but are generally accepted to be ER␣ Ϫ , progesterone receptor (PgR)-negative, and androgen receptor (AR)-positive (18 -21) and Bcl-2-negative (19,22), and many are Her2/neu-negative (23). Moreover some are positive for the gross cystic disease fluid protein-15 (GCDFP-15) (9, 24 -26), a marker that it is, however, not specific for these lesions (16,17,25).…”

ROLE OF MECHANISMS OF VIOLATIONS proliferation and apoptosis in morphogenesis fibrocystic disease of breast

“…И aER и pER сходным образом связываются с эстроген-респонсивным элементом (ERE) ДНК, активируя транскрипцию ERE-регулируемых генов. Однако в зависимости от подтипа рецептора различные промотеры реагируют на эстрогеновую стимуляцию по-разному: aER активирует, а PER угнетает транскрипцию при связывании с комплексами АР-1, SP-1 или белками цАМФ-респонсивного элемента (CRB) [23,30,46]. Показано также, что при патологической пролиферации соотношение aER/pER в ткани молочной железы изменяется: доля aER возрастает, а доля PER уменьшается [49,52,54].…”