首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 140 毫秒
1.
A panel of Japanese and American pathologists reviewed existing histologic material used to study breast cancer risk among the A-bomb survivors in Hiroshima and Nagasaki, a population in which incidence studies have found a strong relationship between breast cancer risk and radiation dose. The primary charge to the panel was to define a body of confirmed cases in the Life Span Study sample of the Radiation Effects Research Foundation that would require little or no review for inclusion in future studies of breast cancer incidence. Broad agreement on histologic type was reached for 298 of 300 confirmed cases. The distribution of histologic types was, overall, similar to that seen in other studies of breast cancer in Japanese women, and did not appear to depend on dose; thus radiation-induced breast cancer appeared to be no different histologically from other breast cancer. Also, no evidence was found of variation in histologic type by city, age at exposure, age at diagnosis, or calendar time.  相似文献   

2.
E Liu  A Thor  M He  M Barcos  B M Ljung  C Benz 《Oncogene》1992,7(5):1027-1032
Amplification and overexpression of the HER2 (c-erbB-2) oncogene was assessed in paraffin-embedded specimens from 27 in situ carcinomas of the breast and from 122 stage II breast cancers. Gene amplification detected in these archival tissues by differential polymerase chain reaction (PCR) was found in 48% of in situ carcinomas and in 21% of stage II lesions (chi 2 = 7.62, p less than or equal to 0.01). In addition, the level of gene amplification correlated with the level of HER2 oncoprotein expression as measured by immunohistochemistry for both in situ cancers (p less than or equal to 0.025) and stage II cancers (p less than or equal to 0.0005). This high incidence of HER2 gene amplification with accompanying overexpression in non-invasive breast tumors suggests that perturbations of the HER2 oncogene are among the earliest and most common genetic lesions in human breast cancer.  相似文献   

3.
Amplification of HER2, C-MYC and CCND1 oncogenes is a hallmark of breast cancer (BC); however, its involvement in the bilateral form of this disease has not been investigated yet. In this study, 50 bilateral BC (biBC) pairs (100 tumors) and 72 control unilateral BC were examined using real-time PCR analysis of microdissected archival tissues. In biBC, the frequency of >3-fold oncogene amplification was 6/100 (6%) for HER2, 6/100 (6%) for C-MYC and 7/100 (7%) for CCND1. Altogether, 18/100 (18%) biBC tumors had increased gene dosage of at least one oncogene. Tumors forming synchronous biBC pairs had amplification in 11/46 cases (24%). In 3 of 8 patients with amplification-positive carcinomas, the amplification was detected in both neoplasms: 2 biBC had concordant activation of the same oncogene (HER2 and CCND1, respectively), and in the remaining case distinct oncogenes were affected (HER2 and C-MYC). In contrast, amplifications in metachronous biBC were strongly discordant: none of 27 first carcinomas carried this abnormality, while the frequency of amplification in second tumors (7/27; 26%) was similar to the one observed in unilateral BC (20/72; 28%). The trend toward concordance of oncogene amplification status in synchronous but not in metachronous biBC pairs can be explained by the nearly identical natural history of the disease in simultaneously arising tumors. The skewed pattern of amplifications in metachronous biBC might be attributed to their association with adverse BC prognosis; it appears that only patients with amplification-negative first BC have sufficient chances to survive until the development of the contralateral carcinoma.  相似文献   

4.
Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10-15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.  相似文献   

5.
Gene expression analysis has identified biologically relevant subclasses of breast cancer. However, most classification schemes do not robustly cluster all HER2+ breast cancers, in part due to limitations and bias of clustering techniques used. In this article, we propose an alternative approach that first separates the HER2+ tumors using a gene amplification signal for Her2/neu amplicon genes and then applies consensus ensemble clustering separately to the HER2+ and HER2- clusters to look for further substructure. We applied this procedure to a microarray data set of 286 early-stage breast cancers treated only with surgery and radiation and identified two basal and four luminal subtypes in the HER2- tumors, as well as two novel and robust HER2+ subtypes. HER2+ subtypes had median distant metastasis-free survival of 99 months [95% confidence interval (95% CI), 83-118 months] and 33 months (95% CI, 11-54 months), respectively, and recurrence rates of 11% and 58%, respectively. The low recurrence subtype had a strong relative overexpression of lymphocyte-associated genes and was also associated with a prominent lymphocytic infiltration on histologic analysis. These data suggest that early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history.  相似文献   

6.
Multiple different oncogenes have been described previously to be amplified in breast cancer including HER2, EGFR, MYC, CCND1, and MDM2. Gene amplification results in oncogene overexpression but may also serve as an indicator of genomic instability. As such, presence of one or several gene amplifications may have prognostic significance. To assess the prognostic importance of amplifications and coamplifications of HER2, EGFR, MYC, CCND1, and MDM2 in breast cancer, we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow-up information. Fluorescence in situ hybridizations revealed amplifications of CCND1 in 20.1%, HER2 in 17.3%, MDM2 in 5.7%, MYC in 5.3%, and EGFR in 0.8% of the tumors. All gene amplifications were significantly associated with high grade. HER2 (P < 0.001) and MYC amplification (P < 0.001) were also linked to shortened survival. In case of HER2, this was independent of grade, pT, and pN categories. MYC amplification was almost 3 times more frequent in medullary cancer (15.9%), than in the histologic subtype with the second highest frequency (ductal; 5.6%; P = 0.0046). HER2 and MYC amplification were associated with estrogen receptor/progesterone receptor negativity (P < 0.001) whereas CCND1 amplification was linked to estrogen receptor/progesterone receptor positivity (P < 0.001). Coamplifications were more prevalent than expected based on the individual frequencies. Coamplifications of one or several other oncogenes occurred in 29.6% of CCND1, 43% of HER2, 55.7% of MDM2, 65% of MYC, and 72.8% of EGFR-amplified cancers. HER2/MYC-coamplified cancers had a worse prognosis than tumors with only one of these amplifications. Furthermore, a gradual decrease of survival was observed with increasing number of amplifications. In conclusion, these data support a major prognostic impact of genomic instability as determined by a broad gene amplification survey in breast cancer.  相似文献   

7.
We investigated the present incidence of lung cancer and its distribution by histologic type in Nagasaki City using Nagasaki Tumor Registry data from the years 1973-1977. The risk of radiogenic lung cancer did not increase significantly in either sex. The difference in relative distribution by histologic type between the exposure and non-exposure groups was not significant. Further analyses should be carried out on the risk present for individuals who were young at the time the bomb was dropped and the effect of exposure distance on the incidence and histologic types of lung cancer in A-bomb survivors.  相似文献   

8.
ABSTRACT: INTRODUCTION: Gene amplification is an important mechanism for activating oncogenes in malignant tumors. Although amplification of HER2, C-MYC, CCND1 and FGFR1 has been reported in breast cancers, their role in the progression of in situ to invasive breast carcinoma is unclear. To investigate this question we compared the amplification frequencies of these genes in pure ductal carcinomas in situ (DCIS), DCIS associated with invasive carcinoma, and invasive carcinomas. METHODS: We performed fluorescence in situ hybridization of the selected genes on tissue microarrays composed of 179 pure DCIS and 438 invasive carcinomas. Two hundred sixteen of the latter had DCIS components, and in those cases we compared gene amplification in the intraductal and invasive components of each carcinoma. RESULTS: The rate of amplification of FGFR1 was higher in invasive carcinomas than in the pure DCIS, but the opposite was true for HER2 amplification. These findings applied consistently to high grade tumors, but not to low-to-intermediate grade tumors. The amplification status of HER2, C-MYC, CCND1 and FGFR1 was generally similar in the matched invasive and DCIS components of the same tumors. However, FGFR1 amplification was more common in the invasive components than in the DCIS components. In survival analyses, FGFR1 amplification was found to be an independent prognostic factor for poor disease-free survival for all patients with invasive carcinoma and for the hormone receptor-positive subgroup. CONCLUSIONS: Amplification of HER2, C-MYC and CCND1 seems to play a role in the early development of breast cancer, but not in its progression. However, the increased frequency of FGFR1 amplification in invasive carcinomas compared to pure DCIS and in the invasive components of individual tumors, and its association with decreased disease-free survival, suggests a role for FGFR1 amplification in the progression of breast cancer including in situ-to-invasive transition, as well as initiation.  相似文献   

9.

BACKGROUND:

Radiation etiology is suggested in the occurrence of basal cell carcinoma (BCC) of the skin among atomic bomb (A‐bomb) survivors. Any genotoxicity, including ionizing radiation, can induce a DNA damage response (DDR), leading to genomic instability (GIN), which allows the accumulation of mutations during tumorigenesis. In this study, the authors evaluated the presence of GIN in the epidermis of survivors as a late effect of A‐bomb radiation.

METHODS:

In total, 146 BCCs, including 23 cases arising from nonexposed skin, were identified in survivors from 1968 to 1999. The incidence rate (IR) of BCC was calculated with stratification by distance in kilometers from the hypocenter (≤1.5 km, 1.6‐2.9 km, and ≥3 km). Nineteen epidermal samples surrounding BCC at the nonexposed sites were collected and tested for p53 binding protein 1 (53BP1) expression with immunofluorescence. 53BP1 rapidly forms nuclear foci at the sites of DNA double strand breaks (DSBs). Because 1 manifestation of GIN is the induction of endogenous DSBs, the level of 53BP1‐focus formation (DDR type) can be considered as a marker for GIN.

RESULTS:

The incidence rate of BCC increased significantly as exposure distance approached the hypocenter. Of the 7 epidermal samples from the proximal group (≤1.5 km), 5 samples predominantly expressed DDR and an abnormal type of 53BP1 expression. In contrast, 4 of 5 samples from the distal group (≥3 km) and all samples from the control group predominantly expressed the stable type of 53BP1 expression in the epidermis.

CONCLUSIONS:

The current results demonstrated the endogenous activation of DDR in the epidermis surrounding BCC in the proximal group, suggesting the presence of a GIN in the survivors as a late effect of A‐bomb radiation, which may indicate a predisposition to cancer. Cancer 2009. © 2009 American Cancer Society.  相似文献   

10.
HER 2/neu expression and gene amplification in colon cancer   总被引:9,自引:0,他引:9  
HER 2/neu is an important oncogene in breast cancer, but the prevalence and significance of HER 2/neu gene amplification in colon cancer have been poorly documented. We have evaluated HER 2/neu gene amplification and protein overexpression in a series of colon cancers to assess the frequency, concordance and clinical significance of these events. HER 2/neu gene copy number was measured in 154 primary colon tumors, 15 liver metastases and matched normal tissues using a quantitative PCR/ligase detection reaction (LDR) technique developed and validated in our laboratory. HER 2/neu copy number was confirmed by fluorescent in situ hybridization (FISH) in all tumors found to have gene amplification. In an independent and blinded fashion, HER 2/neu expression was assessed in paraffin sections from 139 of the tumor specimens using the HercepTest kit. HER 2/neu gene amplification was observed in 4 (2.4%) of the 169 tumor specimens and in none of the normal tissues. There was no apparent association with stage of disease, tumor grade or patient survival. Among 139 cases evaluated by immunohistochemistry (IHC), HER 2/neu overexpression was seen in 5 cases (3.6%). There was extremely high concordance (kappa = 0.852) between gene amplification and protein overexpression. The low prevalence of HER 2/neu gene amplification and protein overexpression suggests that this oncogene plays an infrequent role in the development and progression of colon cancer. These data indicate that the primary mechanism of dysregulated HER 2/neu expression in colon cancer, as in breast cancer, is gene amplification.  相似文献   

11.
To learn more about the role of ionizing radiation in the development of male breast cancer, we evaluated male breast cancer incidence among 45 880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Male breast cancers, diagnosed between January 1, 1958, and December 31, 1998, were identified through the Hiroshima and Nagasaki Tumor Registries. Nine male breast cancers were diagnosed among exposed Life Span Study members (crude rate = 1.8 per 100,000 person-years), and three were diagnosed among nonexposed cohort members (crude rate = 0.5 per 100,000 person-years). A statistically significant dose-response relation was observed (excess relative risk per sievert = 8, 95% confidence interval = 0.8 to 48; P = .01). Our finding of a statistically significant association between ionizing radiation and male breast cancer incidence adds to the very limited information that shows an association between radiation exposure and an increased risk of male breast cancer.  相似文献   

12.
Few epidemiologic studies have investigated the potential role of HER2 in the etiology of breast cancer. We conducted a case-case study of 156 women with incident, invasive ductal carcinoma. Multivariate unconditional logistic regression was used to estimate the odds ratios for a HER2 positive tumor in relation to known and putative risk factors of breast cancer. HER2 status was detected by immunohistochemistry on archival tissue. HER2 positive breast cancers tended to be larger and were less likely to express estrogen receptors, and the incidence rate was higher in patients less than 40 years old. We observed an association between a self-reported history of benign breast disease and the occurrence of HER2 positive breast cancer (OR, 2.1;95% CI, 1.1-4.1). We did not detect associations between HER2 over-expression and family history of breast cancer, parity, late age at first birth, ever having breast fed an infant, or oral contraceptive use. Our findings merit consideration in light of recent evidence of HER2 amplification or over-expression in benign breast disease. Should the link to breast cancer be established, HER2 positive benign breast disease could potentially serve as an early marker for preventive intervention.  相似文献   

13.
The significance of oncogene amplification in primary breast cancer   总被引:1,自引:0,他引:1  
Alterations in the gene copy numbers of the proto-oncogenes HER2/neu and c-myc in primary human breast cancer investigated in 73 patients. We detected amplification of HER2/neu in 17 patient samples and amplification of c-myc in 11, while amplification of both was seen in 6 samples. There was no correlation of age, hormone receptor positivity or tumour size with amplification of either proto-oncogene. Amplification of HER2/neu was significantly correlated with the stage of the disease. HER2/neu amplification was observed in 18.5% and 38% of node-negative and node-positive patients, respectively; the association between HER2/neu amplification and advanced stage of the disease was statistically significant (p = 0.05). Since this is a prospective study, the clinical significance of oncogene amplification is not known. The relatively high frequency of HER2/neu amplification points to a functional role in human breast cancer, particularly in the progression of the disease. The method used in our study allows oncogene amplification to be studied in conjunction with hormone receptor determination and thus may be of value in large clinical trials to determine the significance of oncogene abnormalities in breast cancer.  相似文献   

14.
Breast Cancer Research and Treatment - Our purpose was to explore the prognosis of aggressive breast cancers of the HER2 oncogene amplification (HER2?+) and triple-negative (TN) subtypes...  相似文献   

15.
Moasser MM 《Oncogene》2007,26(45):6469-6487
The year 2007 marks exactly two decades since Human Epidermal Growth Factor Receptor-2 (HER2) was functionally implicated in the pathogenesis of human breast cancer. This finding established the HER2 oncogene hypothesis for the development of some human cancers. The subsequent two decades have brought about an explosion of information about the biology of HER2 and the HER family. An abundance of experimental evidence now solidly supports the HER2 oncogene hypothesis and etiologically links amplification of the HER2 gene locus with human cancer pathogenesis. The molecular mechanisms underlying HER2 tumorigenesis appear to be complex and a unified mechanistic model of HER2-induced transformation has not emerged. Numerous hypotheses implicating diverse transforming pathways have been proposed and are individually supported by experimental models and HER2 may indeed induce cell transformation through multiple mechanisms. Here I review the evidence supporting the oncogenic function of HER2, the mechanisms that are felt to mediate its oncogenic functions, and the evidence that links the experimental evidence with human cancer pathogenesis.  相似文献   

16.
PURPOSE: Germ-line mutations in the BRCA1 tumor suppressor gene predispose to early onset breast cancers with a distinct phenotype characterized by high tumor grade, aneuploidy, high proliferation rate, and estrogen receptor-negativity. The molecular mechanisms and cooperative oncogenes contributing to multistep tumor progression in cells lacking BRCA1 are not well defined. To examine whether C-MYC (MYC), a transforming oncogene associated with genetic instability, contributes to multistep tumor progression in BRCA1-associated breast cancer, we have analyzed tumors from women with hereditary BRCA1-mutated and sporadic breast cancers. EXPERIMENTAL DESIGN: We performed fluorescence in situ hybridization using a MYC:CEP8 assay on formalin-fixed paraffin-embedded tumor tissues from 40 women with known deleterious germ-line BRCA1 mutations and 62 sporadic cases, including 20 cases with hypermethylation of the BRCA1 gene promoter. RESULTS: We observed a MYC:CEP8 amplification ratio >/=2 in 21 of 40 (53%) BRCA1-mutated tumors compared with 14 of 62 (23%) sporadic tumors (P = 0.003). Of the 14 sporadic cases with MYC amplification, 8 (57%) were BRCA1-methylated. In total, MYC amplification was found in a significantly higher proportion of tumors with BRCA1 dysfunction (29 of 60, 48% versus 6 of 42, 14%; P = 0.0003). In a multivariable regression model controlling for age, tumor size, and estrogen receptor status, BRCA1-mutated tumors demonstrated significantly greater mean MYC:CEP8 ratio than sporadic tumors (P = 0.02). CONCLUSIONS: Our data indicate that MYC oncogene amplification contributes to tumor progression in BRCA1-associated breast cancers. Thus, we conclude that the aggressive histopathological features of BRCA1-associated tumors are in part due to dysregulated MYC activity.  相似文献   

17.
Breast cancer survivors have a 60?% higher risk of developing a second primary asynchronous contralateral breast cancer (CBC) compared to women's risk of developing a first primary breast cancer (FBC). However, little is known about how expression of tumor markers in first breast cancers influences CBC risk. We conducted a population-based nested case-control study among women 20-74?years of age diagnosed with a first breast cancer between 1996 and 2008 in western Washington State to evaluate the association between their tumor's estrogen receptor (ER), progesterone receptor (PR) and HER2-neu (HER2) expression, and risk of CBC. The study included 482 cases diagnosed with both a FBC and a CBC and 1,506 control women diagnosed only once with breast cancer identified through our local Surveillance, Epidemiology and End Results (SEER) cancer registry. Compared to the women whose FBC was ER+/PR+, those with ER-/PR- first tumors had a 1.6-fold (95?% confidence interval (CI): 1.2-2.3) increased risk of developing a CBC. When evaluated by joint ER/PR/HER2 status, compared to women with ER+/HER2- first cancers, those with HER2-overexpressing (ER-/HER2+) and triple-negative disease (ER-/PR-/HER2-) had 2.0-fold (95?% CI: 1.1-3.8) and 1.4-fold (95?% CI: 0.9-2.3) elevated risks of developing CBC, respectively. Beyond the known higher risks of mortality among patients diagnosed with more aggressive BC subtypes, here, we observe that they may also have increased risks of developing CBC.  相似文献   

18.
An accurate investigation of the HER2 proto-oncogene is extremely important for the therapy and prognostication of breast cancer. Currently, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are standard methods for this purpose. The aim of this study was to detect the expression and amplification of HER2 in paraffin-embedded samples of breast cancer tissue and to investigate the relationship between HER2 amplification and various clinicopathological parameters in advanced breast cancers. We used FISH to examine the HER2 gene amplification and IHC to examine the expression of HER2 protein, estrogen receptor (ER) and progesterone receptor (PR) in 62 advanced breast cancers. HER2 gene amplification was detected by FISH in 12 breast cancers (19%) and HER2 protein expression with a score of 3+ was detected by IHC in 11 (17%). There was a significant correlation between the HER2 gene amplification and HER2 protein overexpression in breast cancers (P<0.0001). However, some mismatching was evident: 3 cases, negative for the HER2 gene, showed a HER2 protein expression score of 3+ and 2 cases, positive for HER2 gene amplification, had HER2 protein expression scores of 0 and 1+ (negative), respectively. ER and PR were expressed in 41 (66%) and 46 (74%) cancers, respectively. No correlation was observed between the HER2 gene amplification and any of the clinicopathological parameters examined, including age, histopathological type, TNM stage, tumor size, lymph node status, relapse and expression of PR. We observed three patterns among the 6 deceased cases: i) triple negativity for HER2, ER and PR, ii) positivity for HER2 gene amplification with a mismatching HER2 protein expression, and iii) positivity for the HER2 gene amplification with a matching HER2 protein expression score of 2+ or 3+. The triple negative cases and HER2 gene amplification positive cases with a mismatching HER2 protein expression had a poor outcome. These results suggest that in breast cancer, the detection of HER2 gene amplification by FISH is desirable compared with the HER2 protein expression determined by IHC. Moreover, triple negativity for HER2, ER and PR is a potentially very important prognostic marker.  相似文献   

19.
BACKGROUND: Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab. PATIENTS AND METHODS: Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes. RESULTS: BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%-81%] and 47% (95% CI 36%-58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952-7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303-0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368-0.870) by multivariate analysis. CONCLUSION: The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.  相似文献   

20.
Ultraviolet radiation is the major cause of skin cancer, but promotes vitamin D synthesis, and vitamin D has been inversely related to the risk of several common cancers including prostate, breast and colorectum. We therefore computed the incidence of prostate, breast and colorectal cancer following skin cancer using the datasets of the Swiss cancer Registries of Vaud and Neuchatel. Between 1974 and 2005, 6,985 histologically confirmed squamous cell skin cancers, 21,046 basal cell carcinomas and 3,346 cutaneous malignant melanomas were registered, and followed up to the end of 2005 for the occurrence of second primary cancer of the prostate, breast and colorectum. Overall, 680 prostate cancers were observed versus 568.3 expected (standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI): 1.11-1.29), 440 breast cancers were observed versus 371.5 expected (SIR = 1.18; 95% CI: 1.08-1.30) and 535 colorectal cancers were observed versus 464.6 expected (SIR = 1.15; 95% CI: 1.06-1.25). When basal cell, squamous cell and skin melanoma were considered separately, all the SIRs for prostate, breast and colorectal cancers were around or slightly above unity. Likewise, the results were consistent across strata of age at skin cancer diagnosis and location (head and neck versus others), and for male and female colorectal cancers. These findings, based on a population with a long tradition of systematic histologic examination of all surgically treated skin lesions, do not support the hypothesis that prostate, breast and colorectal cancer risk is decreased following skin cancer.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号