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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cysts are associated with an increased risk of breast cancer. Some biomarkers such as estrogen receptor alpha (ERa), progesterone receptor (PR), and cyclin D1, show similar patterns of expression in epithelial cells lining breast cysts as malignant epithelial cells in local and invasive ductal breast cancer. We have attempted to answer two questions: (1) Do epithelial cells lining breast microcysts (cysts which can only be seen with a microscope) express biomarkers in a similar pattern to breast ductal carcinoma in situ and invasive ductal carcinoma? (2) Are breast microcysts precursors of breast cancer or are they part of normal involution of the breast? Seventy two archival open breast biopsy specimens of ductal carcinoma in situ and invasive ductal carcinoma and 32 normal breast biopsies from Australian women who had breast reduction surgery were selected from hospital archives. All specimens were analysed by standard immunohistochemistry for ERa, PR, cyclin D1, bcl-2, p53 and erbB-2 expression. In the same specimens, the pattern of high biomarker expression was very similar for all the above biomarkers in epithelial cells lining microcysts and in both ductal carcinoma in situ and invasive ductal carcinoma c. ErbB-2 was not expressed in normal control specimens. ErbB-2 was expressed in the same specimens in an increasing proportion of normal breast acini, microcysts and cancer cells in 36% of specimens with breast cancer. An apparent progression was observed from normal breast acini, to proliferation of epithelial cells in microcysts, ductal carcinoma in situ and invasive ductal carcinoma in the same specimen. When these findings are considered with other reports we conclude: (1) that epithelial cells lining breast cysts highly express biomarkers in a similar pattern to ductal carcinoma in situ and invasive ductal carcinoma; (2) that some microcysts are not part of normal involution of the breast and in some women may be part of the transition from normal to cancer.
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PMID:Microcysts and breast cancer: a study of biological markers in archival biopsy material. 1235 10

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.
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PMID: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. 1244 74

The vascular endothelial growth factor (VEGF) appears to play an important role in tumor angiogenesis. The p53 and HER-2/neu genes have been thought to regulate VEGF expression. Although the most common genetic alterations described in human breast cancer are p53 gene mutations and HER-2/neu gene amplification, there is a paucity of reports concerning a possible association between VEGF expression and p53 and HER-2/neu expression. Ninety-nine invasive ductal carcinoma cases were examined by immunohistochemical studies with anti-VEGF, anti-p53, anti-HER-2/neu, and anti-CD34 antibodies. Computerized image analysis was used to evaluate the microvessel density (MVD). Eighty-eight tumors (88.9%) were classified as being VEGF positive. Twenty-five tumors (25.3%) showed p53 protein expression, while 36 tumors (35.4%) expressed the HER-2/neu protein. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). The tumors expressing VEGF had a significantly higher MVD than those that did not (P < 0.05). VEGF expression was significantly associated with p53 protein expression (P < 0.01). In double VEGF and p53 immunohistochemical stained sections, the two markers were generally expressed in the same tumor cells. The cancer stage was the only independent prognostic factor of disease-free and overall survival. The authors' results suggest that VEGF expression plays a role in promoting angiogenesis in invasive ductal carcinoma of the breast, and p53 is likely to be involved in regulating VEGF expression.
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PMID:Expression of vascular endothelial growth factor in invasive ductal carcinoma of the breast and the relation to angiogenesis and p53 and HER-2/neu protein expression. 1260 95

Young women with breast cancer have a more unfavorable outcome and advanced disease than older women. This study was initiated to determine the difference in tumor biology between younger and older groups. One hundred fifty-five patients with invasive ductal carcinoma, not otherwise specified, comprised the study group, including 50 women aged less than 35 years, 50 aged 36 to 50 years, and 55 aged more than 50 years. Histopathologic parameters, including tumor size, combined histologic grade, and axillary lymph node status, were studied. Biomarkers, including estrogen receptor status, tumor proliferation rate as determined by Ki-67, and gene expressions of c-erbB-2, p53, bcl-2, and BRCA1, were determined by immunohistochemistry. Comparisons of the distribution of these parameters in three age groups were performed. Breast cancer occurring in women aged less than 35 years had a significantly higher incidence of large tumor, high proliferation rate, and loss of nuclear BRCA1 expression (44.0% versus 22.0% or 23.6%) than in the two older age groups. Breast cancer in women aged less than 35 years also had higher histologic grade and higher frequency of bcl-2-negative tumor than that found in the 36- to 50-year age group. No difference was found in lymph node status and c-erbB-2 and p53 gene expressions between the age groups. Loss of BRCA1 nuclear expression significantly correlated with higher histologic grade and high Ki-67 index (P < 0.05) in group A. These findings suggested that women aged less than 35 years have frequent loss of nuclear BRCA1 expression, which may be responsible for the specific tumor biology different from older women. However, c-erbB-2 and p53 gene expressions seem to have no important role in the adverse tumor behavior of breast cancer in young women.
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PMID:Frequent loss of BRCA1 nuclear expression in young women with breast cancer: an immunohistochemical study from an area of low incidence but early onset. 1260 98

Our report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.
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PMID:Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor. 1262 31

There are a large number of stable pancreatic ductal carcinoma cell lines that are used by researchers worldwide. Detailed data about their differentiation status and growth features are, however, often lacking. We therefore attempted to classify commonly used pancreatic carcinoma cell lines according to defined cell biological criteria. Twelve pancreatic ductal adenocarcinoma cell lines were cultured as monolayers and spheroids and graded according to their ultrastructural features. The grading system was based on the integrity of membrane structures and on the presence of mucin granules, cell organelles, nuclear and cellular polymorphism, cell polarity, and lumen formation. On the basis of the resulting scores the cell lines were classified as well, moderately, or poorly differentiated. In addition, immunocytochemistry was performed for the markers cytokeratin 7, 8, 18, 19, carcinoembryonic antigen, MUC1 MUC2, MUC5, and MUC6. The population doubling time of monolayer cultures, determined by a tetrazolium salt based proliferation assay was correlated with the ultrastructural grade. The grading of the ultrastructural features of the monolayers, and particularly of the spheroids, revealed that Capan-1 and Capan-2 cells were well differentiated; Colo357, HPAF-2, Aspc-1, A818-4, BxPc3, and Panc89 cells were moderately differentiated and PancTu-I, Panc1, Pt45P1, and MiaPaCa-2 cells poorly differentiated. Membrane-bound MUC1 staining was a characteristic of well differentiated cell lines. The population doubling time of the monolayer cultures was related to the differentiation grade. No relationship was found between the p53, K-ras, DPC4/Smad4, or p16(INK4a) mutation status and the grade of differentiation. We conclude that the proposed ultrastructural grading system combined with the proliferative activity provides a basis for further comparative studies of pancreatic ductal adenocarcinoma cell lines.
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PMID:A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform. 1269 24

As male breast cancer remains rare entity (less than 1% of cases of breast cancer), most of our current knowledge of it has been extrapolated from its female counterpart. The prevalence of male breast cancer increases with age, and the presentation occurs at an average age of approximately 60 years, 10 years older than in females with the disease. The majority of patients present with a painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in diameter. There may be fixation to skin. Mammography and ultrasonography are useful to distinguish between breast cancer and gynecomastia. Pathologically, invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is rare. Modified radical mastectomy is a principal surgical approach, and adjuvant therapy has been advocated in men based on the beneficial results of it in women. Hormonal manipulations constitute an essential part of adjuvant therapy, as male breast cancers have a high rate of hormone-receptor positivity. Although orchiectomy was practiced in the past, today, tamoxifen is the standard hormone therapy. With respect to systemic chemotherapy, the most common regimens are CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy, or radiotherapy can be administered for palliative purposes. Several selective aromatase inhibitors are now available; however, there are limited data regarding their efficacy in men. The prognosis does not seem to be poor compared to that of females when age and stage are matched. Further studies are needed to characterize the biologic and molecular properties of male breast cancer and their prognostic significance, and to devise optimal treatment strategies. However, it is interesting to note that p53 and c-erbB-2, are expressed and angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients can carry BRCA2 mutations.
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PMID:[Male breast cancer]. 1279 89

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.
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PMID:Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases. 1282 6

Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.
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PMID:Medullary breast carcinoma: prognostic implications of p53 expression. 1284 78

The aim of this prospective study was to evaluate biological markers, their correlation with response and outcome, and the change in these markers under the influence of preoperative chemotherapy (PCT) in patients with a large primary breast cancer. One hundred and thirty-five women were treated with PCT, followed by locoregional therapy and adjuvant treatment. Estrogen receptor (ER), progesterone receptor (PgR), HER-2, p53, and cathepsin D were determined by immunohistochemistry (IHC) before and after PCT. The overall response (OR) was 70% and the pathologic complete response (pCR) was 13%. Forty-four percent of the patients could be offered breast-conserving surgery (BCS). At a median follow-up of 50 mo the overall survival is 82% and the disease-free survival is 70%. No local recurrence (LR) has developed following BCS. Invasive ductal carcinoma (IDC) was more frequently ER-negative and HER-2-positive than invasive lobular carcinoma (ILC). P53-negative and ER-negative patients seemed to be more chemosensitive compared to p53-positive patients (74% vs 53%) and ER-positive patients (75% vs 65%), but this difference did not reach statistical significance. A trend toward higher complete pathologic remission rate was seen for ER-negative patients (p = 0.0609). PgR, HER-2, and cathepsin D were not related to response. The pattern of biological markers did not change with PCT, making repeated determination useless.
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PMID:The role of biological markers as predictors of response to preoperative chemotherapy in large primary breast cancer. 1451 71


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