Cell cycle related proteins in hyperplasia of usual type in breast specimens of patients with and without breast cancer (original) (raw)
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Expression of cell cycle proteins in male breast carcinoma
World Journal of Surgical Oncology, 2010
Introduction: Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints. Methods: 75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years . Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).
Cell cycle proteins do not predict outcome in grade I infiltrating ductal carcinoma of the breast
… journal of cancer, 2000
Infiltrating ductal mammary carcinomas are histologically graded according to their extent of differentiation. Welldifferentiated, grade I, tumours have low proliferative activity, usually form tubules and exhibit little nuclear pleomorphism. Despite an apparently reassuring morphology, 10 -15% of grade I ductal carcinomas metastasise, albeit after a prolonged period. Recent evidence supports the view that evolution to higher grade malignancies occurs rarely and that grade I tumours are biologically distinct from grade III tumours. We have examined a series of 148 grade I ductal carcinomas in order to ascertain whether information about the level of expression of cyclin D1, p27, p53, oestrogen receptor status (ER) or proliferative activity could be used to identify those patients with a poor outcome. The majority of tumours expressed high levels of cyclin D1, p27 and ER, low levels of p53 and had low Ki-67 expression and mitotic counts. Cyclin D1, p27 and ER expression were all significantly correlated with each other but not with p53 (cyclin D1 correlation with ER, p ؍ 0.01; cyclin D1 correlation with p27 and ER correlation with p27 both p < 0.0001). Cyclin D1 and ER were also both correlated with Ki-67 (p ؍ 0.01 and p < 0.0001) but not with mitotic count. Our results suggest that cyclin D1, ER and p27 are all markers of well-differentiated tumours and that their detection is related to proliferative activity in a manner reflecting their functional role within the normal cell cycle. However, none of the proteins or markers of proliferative activity were sensitive enough to predict which patients were likely to have a poor outcome.
The prognostic impact of some cell cycle regulatory proteins in Egyptian breast cancer patients
Journal of the Egyptian National Cancer Institute, 2006
The particular goal of this work is to study some cell cycle regulatory proteins and their potential impact on prognosis of breast cancer; p53, cyclin D1 and p27 are potential effectors being the major contributors to the control of the restriction (R) check point of the cell cycle. We also aimed to evaluate different techniques used to detect these cell cycle proteins. Forty five breast cancer patients as well as 10 controls with non malignant pathology were assessed for cell cycle regulators each by 2 different techniques; p53 was assessed by enzyme immunoassay (EIA) and immunohistochemistry (IHC), cyclin D1 by Western Blotting (WB) and IHC and p27 by WB and IHC. The cut-off was calculated as the mean of the normal controls +2 SD. Patients were followed up for 4 years and their laboratory data were correlated with different clinical parameters and with other studied regulators. Eighty seven percent of cases (39/45) were positive for p53 by EIA with a range from 20 to 4300, and a m...
Breast Cancer Research and Treatment, 2003
Molecular markers predicting response to preoperative chemotherapy would be of major clinical relevance in breast cancer. Therefore, we studied the relationship between the expression of cell cycle regulatory proteins and clinical outcome in breast cancer patients receiving preoperative chemotherapy. Expression of p2lWaf1, p27KiP1, p53, cyclin D3 and Ki-67 was determined in breast carcinomas by means of immunohistochemistry both prior and after preoperative chemotherapy. Expression data were compared with both clinical parameters and response to preoperative chemotherapy with either cyclophosphamide/methotrexate/5-fluorouracil (CMF, n = 29) or epirubicin/docetaxel (ED, n = 36). In paired samples before and after preoperative chemotherapy, the percentage of p21Waf1, p27Kip1, p53 and cyclin D3 positive nuclei of tumor cells in postchemotherapy specimens was significantly higher than the percentage in prechemotherapy samples but no change in Ki-67 expression was observed. High Ki-67 expression (p = 0.02), negative estrogen receptor status (p = 0.01) and negative progesterone receptor status (p = 0.04) were associated with complete pathologic response to chemotherapy, whereas the other markers did not predict response. In conclusion, expression levels of p21Waf1, p27Kip1, p53 and cyclin D3 significantly increased after preoperative chemotherapy in breast carcinomas but only high Ki-67 expression, negative estrogen receptor status and negative progesterone receptor status were associated with complete pathologic response to preoperative chemotherapy.
Research in Veterinary Science, 2009
Proteins controlling cell growth, differentiation, apoptosis, and oncogenic stress are often deregulated in tumor cells. However, whether such deregulations affect tumor behavior remains poorly understood in many tumor types. We recently showed that the urothelium-specific expression of activated Hras and SV40 T antigen in transgenic mice produced two distinctive types of tumors strongly resembling the human superficial papillary tumors and carcinoma in situ of the bladder, respectively. Here we assessed the expression of a key set of cell cycle regulators in these mouse tumors and in a new transgenic line expressing a cyclin D1 oncogene in the urothelium. We found that urothelia of the wild-type and cyclin D1 transgenic mice exhibited a profile of cell cycle regulators found in quiescent (G 0 ) cells, indicating that urothelium overexpressing the cyclin D1 (an 8-fold increase) is reminiscent of normal urothelium and remains slowcycling. Low-grade superficial papillary tumors induced by activated H-ras had no detectable Rb family proteins (Rb, p107, and p130) and late cell cycle cyclins and kinases (cyclin A, E, and CDK1), but had increased level of p16, p53, and MDM2. These data suggest that the inactivation of the Rb pathway plays an important role in H-ras-induced superficial papillary tumors and that oncogenic H-ras can induce a compensatory activation of alternative tumor suppressor pathways. In contrast, carcinoma in situ of the bladder induced by SV40 T antigen had increased expression of cell cycle regulators mainly active in post-G 1 phases. The fact that phenotypically different bladder tumors exhibit different patterns of cell cycle regulators may explain why these tumors have different propensity to progress to invasive tumors. Our results indicate that the transgenic mouse models can be used not only for studying tumorigenesis but also for evaluating therapeutic strategies that target specific cell cycle regulators. (Cancer Res 2005; 65(4): 1150-7)
Protein expression patterns of cell cycle regulators in operable breast cancer
PLOS ONE
Background-Aim To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes. Methods Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials. Jaccard distances were computed for the markers and the resulted matrix was used for conducting unsupervised hierarchical clustering, in order to identify distinct groups correlating with prognosis. Results Luminal B and triple-negative (TNBC) tumors presented with the highest and lowest levels of cyclin D1 expression, respectively. By contrast, TNBC frequently expressed Cyclin E1,
Pathology & Oncology Research
We aimed to analyze the expression of cell-cycle regulation markersminichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) − in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (p < 0.01 and p < 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (p = 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. The pattern of cell-cycle activity could also be useful for predicting early relapse, but our findings need to be further substantiated in larger patient cohorts.
Cancer research, 1997
Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospective series of 202 patients with stage T1a,b invasive breast carcinomas was evaluated. The clinicopathological features (age, histological grade, extensive in situ carcinoma, hormone receptor status, and nodal metastasis) as well as microvessel density and the expression of c-erb-B2, p53, MIB-1/Ki-67, and cdc25B were assessed. In addition, expression of the cell cycle inhibitor p27 was evaluated. Nineteen patients (18% of patients who had axillary dissection) had locoregional lymph node metastases. Forty-two % of them died of disease (median survival, 112 months), whereas mortality was 11% in node-negative patients (median survival, 168 months; P = 0.0055). Patients w...
Cell cycle alterations and their relationship to proliferation in apocrine adenosis of the breast
Histopathology, 2009
Cell cycle alterations and their relationship to proliferation in apocrine adenosis of the breast Aims: Apocrine adenosis (AA) is generally considered a benign disease of the breast. However, recent studies have suggested a precancerous potential for some of these lesions. The aim was to investigate the status of cell cycle proteins previously reported to be deregulated in breast cancer to identify their possible role in AA. Methods and results: The cases were categorized into AA without atypia (NAA) and atypical AA (AAA). Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki67 was determined in 29 NAA and 16 AAA cases. Cyclin D1, p21 and cyclin A were overexpressed in 58.6%, 51.7% and 31.8% of the NAA cases, respectively, whereas 81.3%, 62.5% and 41.7% of the AAA cases showed overexpression of cyclin D1, p21 and cyclin A, respectively. All cases were negative for p16, whereas pRb was expressed in all cases. Furthermore, proliferation in AA (4.5%) was significantly higher than that of normal breast epithelium (1%). There was no statistical significance in the degree of proliferation between the NAA (3.7%) and AAA (4.8%) groups. Conclusions: The study indicates that NAA and AAA are biologically similar. A subset of AA defined by increased proliferation and significant cell cycle alterations may be susceptible to oncogenesis.