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1.
Abstract: Apocrine lesions of the breast are not uncommon. Limited studies have suggested that apocrine cells may be under the influence of an androgenic, rather than an estrogenic, regulatory system. Furthermore, a recent study has shown that metaplastic apocrine cells of the breast lack expression of bcl-2, a B-cell leukemia/lymphoma gene protein whose expression in the breast is believed to be regulated by estrogen. This study was undertaken to immunohistochemi-cally assess the status of expression of estrogen receptor (ER), progesterone receptor (PR), bcl-2, and androgen receptor (AR), in a series of mammary apocrine lesions ranging from simple metaplasia to metastatic carcinoma, and to determine whether there is any possible interrelationship or correlation between the expression of these hormone receptors and that of bcl-2. Among 102 apocrine lesions (68 benign and 34 malignant) evaluated, 100 (98%) were ER and PR negative; only two intraductal carcinomas (IDCA, 2%) were weakly positive for ER and PR. Bcl-2 was detectable only in these two IDCA, but not in any of the other apocrine lesions. In contrast, AR positivity was evident in 15 of 16 (94%) benign apocrine lesions and 18 of 25 (72%) cancerous apocrine lesions (13 of 16 IDCA, 5 of 8 invasive carcinomas, and 0 of 1 metastatic carcinoma) evaluated; all 7 AR negative cancerous lesions (3 IDCA, 3 invasive carcinomas, and 1 metastatic carcinoma) were poorly differentiated with pronounced atypia. These results suggest that apocrine differentiation appears to be associated with retention of AR positivity and a reversal of the usual mammary hormone receptor expression profile for ER, PR, and bcl-2 oncoprotein. These findings warrant exploration of the value of androgenic hormone manipulations in management of AR-positive apocrine carcinomas.?  相似文献   

2.
OBJECTIVE: To estimate the value of estrogen receptor (ER) in benign breast diseases and to find out if the response of benign breast diseases to danazol depends on the ER status of the tissue. DESIGN: Prospective study. SETTING: University hospital, India. MATERIAL: Samples of tissue from benign breast lesions, 40 fibrocystic disease and 10 fibroadenomas. INTERVENTIONS: Enzyme immunoassay for the presence of cytosolic ER. MAIN OUTCOME MEASURES: ER concentrations, and correlation with effect of treatment with danazol. RESULTS: Fibrocystic disease and fibroadenomas showed 30% and 40% ER positivity, respectively. The mean (SD) ER concentration was significantly higher in premenopausal than postmenopausal patients 14.75 (3.79) fmol/mgm compared with 6.2 (1.59) fmol/mg (p < 0.05). All ten patients with mastalgia who had ER-positive lesions (n = 26) responded to danazol, compared with 6 of 16 patients who had ER-negative lesions (p < 0.05). Lesions with diffuse fibrosis (n = 14) and five with lymphocytic infiltration on histology were all ER-negative. CONCLUSION: The patients with ER positive breast disease responded better to danazol than patients with ER negative breast disease.  相似文献   

3.
Abstract: The purpose of this study was to determine biological variable profiles and survival experiences associated with different combinations of estrogen receptor (ER) and progesterone receptor (PR) status (ER+PR+, ER+PR-, ER-PR+, ER-PR-). Data were collected and provided by the State Health Registry (SHR) of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Significant associations were determined for individual prognostic variables with each ER/PR categories, and overall survival was compared between each ER/PR category. Multiple logistic regression analyses were conducted to determine all significant prognostic variables associated with each ER/ PR category. All women diagnosed with primary breast cancer in Iowa from 1990 through 1992 were included in this study (N = 6, 178). In unadjusted analyses, Caucasian woman and older women were significantly more likely to be ER + PR+, while African American women and younger women were significantly more likely to be ER-PR-. In multivariate analyses, each ER/PR category was associated with distinct profile of age, menopausal status, histologic grade, and histology. Survival was best for women in the ER+PR+ group, followed, in decreasing order, by ER+PR-, ER-PR+, and ER-PR-. In this population-based study of primary breast cancer, combined hormone receptor status was a significant prognostic determinant for primary breast cancer, and was associated with distinct biological variables and survival experiences. In combination with other variables such as age, menopausal status, tumor histologic grade, and tumor histology, combined hormone receptor status can provide important prognostic information to the clinician.?  相似文献   

4.
Using a fluorometric assay based on the activation of human plasminogen, plasminogen activator (PA) activity was measured in cytosolic and lysosomal extracts prepared from normal, benign hyperplastic (BPH), and carcinomatous human prostates. In all three types of prostatic tissue, the lysosomal extracts had much higher concentrations of PA activity than did the cytosolic extracts. The mean PA activity in lysosomal extracts of the carcinomatous prostates was 170% and 85% higher than that measured in normal and BPH prostates, respectively (Student's t-test, p less than .05). With prostatic carcinoma and BPH specimens there was an inverse (negative) relationship between lysosomal PA activity and the nuclear concentration of androgen-receptors (correlation coefficient, -0.84). By comparison in specimens of human breast tumors, there were weakly positive correlations between PA activity and either estrogen (ER) or progestin (PR) receptors (correlation coefficients of + 0.23 and + 0.54, respectively). While as a group ER+, PR+ breast tumors had higher PA activity that ER+, PR- or ER-, PR- tumors, the differences were not statistically significant (Student's t-test, p greater than .05). Thus in breast tumors, it is uncertain whether high levels of PA activity are indicative of hormonal dependence. However, our findings with prostatic tumors infer that in contrast, high concentrations of this enzyme may reflect a malignant phenotype characterized by a decrease in both androgen responsiveness and differentiation.  相似文献   

5.
目的探讨乳腺癌针吸细胞学激素受体检测的临床意义。方法应用单克隆抗体免疫组化法对42例乳腺癌患者的针吸细胞学涂片与组织切片检查结果对照。结果针吸细胞学涂片与其石蜡切片雌激素受体(ER)、孕激素受体(PR)检测的总符合率为83.3%、80.95%,二者差异无统计学意义。结论乳腺癌针吸细胞涂片检测激素受体结果与组织切片同样可靠。这种方法简便易行,安全性好,对不适合手术的患者的治疗方案选择具有重要的意义。  相似文献   

6.
Daniel W. Visscher  MD    Niru Padiyar  MD    Dan Long  HT  Pam Tabaczka  BS  MT 《The breast journal》1998,4(6):447-451
Abstract: The growth of invasive breast carcinoma is facilitated by abnormal expression of estrogen receptor (ER), however, the status of ER during disease histogenesis is poorly defined. The extent of ER immunostaining (expressed as percentage of positive cells) was semiquantitated in the invasive (ICA) and corresponding in situ (CIS) components of 50 formalin-fixed, paraffin-embedded breast carcinomas and then compared to staining in normal terminal duct lobular units (TDLU) or hyperplastic lesions (if present) in the same tissue sections. Morphologically normal TDLUs from most cases (61%) exhibited ER staining in 11–30% of epithelial cells; only 10% of the cases had TDLUs demonstrating immunoreactivity in more than 50% of cells. In contrast, 80% of the hyperplastic lesions showed ER staining in more than 30% of epithelial cells, with 44% demonstrating immuoreactivity in more than 50% of epithelial cell nuclei (p = 0.01, chi-square test). Although most in situ carcinomas showed even more extensive ER staining than hyperplasias (>70% of cells were positive in 50% of cases), a significant subset (28%) of CIS exhibited staining in less than 10% of cells (p = 0.002, chi-square test). Invasive carcinomas were less often extensively immunoreactive (i.e., >50% of cells positive) than CIS (32% versus 58% for CIS) and there were five cases (10%) in which the CIS component was ER positive but the invasive component was ER negative. Finally, ER-positive carcinomas were significantly more often accompained by extensive CIS and/or proliferative breast disease (p = 0.007 and 0.003, respectively). The divergent levels of ER expression observed between premalignant, preinvasive, and invasive lesions suggests that inappropriate regulation of hormone receptors may be a factor that promotes early growth or progression in breast neoplasia, and ER-positive breast carcinomas are characterized by a different, possibly lengthier, histogenesis than ER-negative malignancies with a greater frequency of background hyperplastic lesions and a larger preinvasive component.  相似文献   

7.
Abstract: This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR?) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR? patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR? patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy, but significantly better overall outcome. For both HR? and HR+, addition of NAT for HER2+ tumors results in both a superior response and outcome.  相似文献   

8.
Breast carcinomas in both genders share pathological features, although differences in incidence, prognosis and survival are reported. Expression of 33 genes was investigated in male and female breast carcinomas in association with ER, PR, HER-2/neu and EGF-receptor. Among 98 male breast cancers, 82 were ER+ and 78 were PR+. ER and PR protein levels were greater in males compared to females, although no differences were observed in ESR1 and PGR expression. A difference was observed in binding affinities of PR but not ER between genders. No differences were observed in HER-2/neu, EGFR protein, or patient age. Expression of NAT1, TBC1D9, IL6ST, RABEP1, PLK1 and LRBA was elevated in carcinomas of males compared to those of females, in which ER status appeared to be related to expression. Over-expression of protein products of these genes represents novel molecular targets for development of gender-specific therapeutics and companion diagnostics.  相似文献   

9.
10.
Expression of c-kit proto-oncogene product in breast tissue   总被引:3,自引:0,他引:3  
The proto-oncogene c-kit encodes a transmembrane tyrosine kinase growth factor receptor. Stem cell factor, the receptor ligand, plays an important role in the development of certain neoplasms. c-kit is selectively and competitively bound by STI-571, a newly developed tyrosine kinase inhibitor. Several investigators report conflicting results concerning its expression, especially in malignant breast lesions. The objective of this study was to better characterize the expression of c-kit within the spectrum of breast epithelium (normal breast epithelium, nonneoplastic lesions, and breast carcinoma). Seventy-seven randomly selected breast tissue samples, each containing normal breast epithelium (21), invasive breast carcinoma (41), in situ breast carcinoma (29), papilloma (8), fibroadenoma (5), fibrocystic change (11), and/or metastatic breast carcinoma (4), were immunostained with polyclonal rabbit antihuman c-kit (Dako, Carpenteria, CA) at a dilution of 1:200. The staining was interpreted as negative if no cells were immunoreactive, weak positive if 5% of the cells were immunoreactive, and positive if more than 5% of the cells were immunoreactive. Appropriate positive and negative controls were used. The observed staining was cytoplasmic, with highlighting of the nuclear membrane. Normal breast epithelium was positive in all cases. More than half of the cases of hyperplastic changes and benign neoplasms (fibroadenoma and papilloma) were positive. Only 10% of invasive and in situ carcinomas showed positivity for c-kit. c-kit is consistently expressed in normal breast epithelium, variably expressed in benign breast lesions, and poorly expressed in breast carcinoma. These data suggest that c-kit may play a role in breast tumor progression and may therefore have diagnostic, prognostic, and therapeutic implications.  相似文献   

11.
▪  Abstract: The immunohistochemical staining patterns of type IV collagen (TIVC) and smooth muscle actin (SMA) were studied in benign and malignant breast lesions in order to assess their usefulness in the differential diagnosis of difficult lesions. Eighty-six in situ breast carcinomas (8 with microinvasion; 1 diagnosed after immunostaining) and 58 invasive carcinomas, with associated benign lesions including 87 nonproliferative fibrocystic changes, 19 sclerosing adenosis, 17 atypical hyperplasias, 7 benign papillary proliferations, 6 radial scars, and 105 normal mammary tissue, were studied. TIVC and SMA were concomitantly positive throughout in 94% of benign tissues, in 16% of in situ carcinomas, but in none of the invasive carcinomas. Conversely, both markers were negative in 66% of invasive carcinomas, but in none of the benign breast tissue and none of the in situ carcinomas. In 6% of the benign tissues, in 21% of in situ carcinomas, and in 34% of invasive carcinomas only one of the markers was positive. In the remaining 63% of the in situ carcinomas there were discontinuities of the staining of both markers. It is therefore suggested that a diagnosis of invasive malignancy can be confirmed when both markers are negative, and ruled out when both markers are positive. This is particularly useful, in our experience, in the identification of small foci of invasion. The stains are useful when used in parallel, whereas they may be misleading when used singly. The staining pattern is not useful in the differential diagnosis of atypical hyperplasia and in situ carcinoma.  ▪  相似文献   

12.
The 8th edition of the American Joint Committee on Cancer (AJCC) staging guidelines combine traditional TNM system with biomarkers to reflect our current understanding of tumor biology and targeted therapy. In this study, we investigated the impact of the TNM + Biomarkers staging system and the additive value of Oncotype Dx? genomic profile recurrence score (RS) (TNM + Biomarkers+RS <11) for the staging of breast cancer (BC) using data from two tertiary referral cancer centers. Compared to TNM alone, the TNM + Biomarkers system changed the stage group in 32.7% of BCs (27% downstage, 5.7% upstage). Most (98.3%) of the downstaged BCs were estrogen receptor (ER)+/progesterone receptor (PR)+, whereas 78% of the upstaged BCs were ER?/PR?/human epidermal growth factor receptor 2 (HER2)?. Compared to TNM + Biomarkers staging, the addition of genetic profile data (TNM + Biomarker+RS <11) downstaged only <1% BCs. Our analysis suggests that for T1‐T2N0 ER+/HER2? BCs, Oncotype Dx? RS <11 provides added value as a staging parameter only in a very small group of cases compared to TNM + Biomarkers alone.  相似文献   

13.
目的:探讨不同乳腺病变组织中脾酪氨酸激酶(Syk)表达差异,并分析Syk表达与乳腺癌临床及其他病理学指标的关系。方法:用免疫组化法检测20例纤维囊性乳腺病组织、16例乳腺DIN2组织(导管原位癌,中级别)、168例乳腺浸润性导管癌组织及95例癌旁组织中Syk蛋白的表达,并检测乳腺癌组织中ER、PR、p53、HER2/neu表达。结果:纤维囊性乳腺病组织、乳腺DIN2组织、乳腺癌组织及其癌旁组织中Syk阳性表达率分别为90.00%(18/20例)、50.00%(8/16例)、34.52%(58/168例)及78.95%(75/95例)。乳腺癌组织中Syk阳性表达率较纤维囊性乳腺病组织(P〈0.05)及乳腺癌旁组织(P〈0.05)明显降低。乳腺DIN2组织中Syk阳性表达率较纤维囊性乳腺病组织(P〈0.05)及乳腺癌旁组织(P〈0.05)明显降低。Syk表达与肿瘤大小、组织学分级、淋巴结转移、肿瘤分期及ER、PR、p53、HER2/neu表达结果均无相关性。结论:Syk在纤维囊性乳腺病、癌旁组织、癌前期病变和乳腺癌组织中的阳性表达率依次降低。  相似文献   

14.
目的探讨双侧原发性乳腺癌癌基因Her-2、p53、nm23及其雌激素受体(ER)、孕激素受体(PR)的表达情况,了解双侧原发性乳腺癌的生物学行为。方法研究分析20例双侧原发性乳腺癌相关癌基因Her-2、p53、nm23及其ER、PR表达情况,并与同期单侧乳腺癌比较。结果在同期650例乳腺癌中,双侧原发性乳腺癌20例,占3.07%,第一癌的ER、PR阳性率分别为60%和50%,第二癌的ER、PR阳性率分别为50%和40%,分别与同期单侧乳腺癌比较差异无统计学意义(P>0.05),第一和第二癌Her-2阳性表达率分别为40%(8/20)和30%(6/20);p53的阳性表达率分别为40%(8/20)和40%(8/20);nm23的阳性表达率分别为60%(12/20)和60%(12/20),它们与同期单侧乳腺癌比较差异均无统计学意义(P>0.05)。结论双侧原发性乳腺癌的相关癌基因Her-2、p53、nm23及其ER、PR受体改变没有特异性,与单侧乳腺癌的生物学行为相仿,治疗上应采取积极治疗措施。  相似文献   

15.
运用S-P免疫组化法对30例手术治疗的男性肝细胞癌患者癌组织,癌周组织及20例良性病变肝组织的雄激素受体,雌激素受体以及孕激素受体进行了检测。结果;肝癌组织AR阳性率80.0%,显著高于癌周组织及良性病变肝组织,P〈0.01,后两者比较无显著性差异;癌组织ER阳性率为43.3%,显著低于癌周组织,P〈0.01,与良性病变肝组织比较无差异;PR阳性率在3种组织中比较无显著性差异。  相似文献   

16.
Abstract: Estrogen and progesterone are necessary for lobulo-alveolar development of the human breast, and there is an abundance of epidemiologic literature implicating estrogen and possibly progesterone exposure as promoters of breast malignancy. The investigation of estrogen receptor (ER) and progesterone receptor (PgR) distribution in normal and benign breast tissue may be a measure of susceptibility of the tissue to these hormones. Earlier data from radioligand binding assays showed that benign breast tissue expressed little or no ER; newer immunohistochemical (IHC) methods have led to the investigation of benign breast tissue from at least 1243 women in 12 studies in the last 9 years. These show that the level of expression of ER and PgR in normal breast epithelium is significantly lower than in receptor positive carcinomas. Immunostaining patterns for both receptors show a great deal of heterogeneity. There is general agreement that stromal and myoepithelial cells are negative for both ER and PgR. A growing body of evidence suggests that PgR is the dominant sex steroid receptor in the normal breast. Mean values for PgR positive cells in breast epithelium range from 24% to 29%; ER is positive by IHC in 3% to 15.6% of normal breast epithelial cells. No firm conclusions are possible as yet regarding overexpression in proliferative epithelium. There is agreement that the proportion of ER positive cells declines in the second half of the menstrual cycle, but there is no clear cut relationship between PgR positivity with the menstrual cycle. Oral contraceptive use appears to decrease the proportion of ER positive cells, and increase mammary epithelial proliferation. A recent case-control analysis of epithelial ER and PgR status reports an association of ER positive benign epithelium with the presence of cancer in the breast. Future research should include a systematic quantitative analysis of receptor expression in epithelial proliferative lesions, and the longitudinal follow-up of women who have had receptor testing on benign breast tissue.  相似文献   

17.
The objectives of this study were to document the oestrogen and progesterone receptor (ER & PR) status of breast cancer in the Indian population (as done by immunohistochemistry on paraffin blocks), and correlate the steroid receptor status of breast cancer with all relevant patient and tumour characteristics. Our current data have been compared with previously published data from other centres. In contrast to the higher rates reported in the Western literature, only 32.6% of our tumours were ER positive and 46.1% were PR positive. Tumours were separated into four categories: ER+PR+ (25%), ER+PR- (7.4%), ER-PR+ (21.1%) and ER-PR- (46.5%). ER and PR immunoreactivity increased with advancing age, and correlated with the presence of elastosis. Infiltrating lobular carcinoma, mucinous carcinoma, and mixed tumours were more frequently ER & PR positive. High-grade infiltrating duct carcinomas, pure comedo ductal carcinoma in situ, and medullary carcinoma were predominantly ER & PR negative. The presence of necrosis and lymphovascular invasion showed an inverse relationship with ER and PR reactivity.  相似文献   

18.
Abstract:  The family of insulin-like growth factor binding proteins (IGFBPs) comprises six members which bind and regulate the functions of IGFs. Overexpression of IGFBP2 and IGFBP5 contributes to the invasiveness and progression of several human cancers, but their roles in the metastasis of breast cancer have not been investigated in detail. To determine their roles, we examined IGFBP2 and IGFBP5 expression levels in 164 T1 breast carcinomas using tissue microarrays and immunohistochemistry. The specimens were divided into those with (N1) or without (N0) axillary lymph node involvement. The results were associated with clinicopathologic parameters and prognostic molecular markers. No or very low expression of IGFBP2 and IGFBP5 was detected in normal breast epithelium or benign breast tissue with fibrocystic change. Moderate to strong cytoplasmic staining for IGFBP2 and IGFBP5 was detected in 49.1% and 50.3% of T1 invasive breast carcinomas, respectively. T1N1 carcinomas were more frequent to have moderate and strong-positive staining for IGFBP2 and IGFBP5 than in T1N0 carcinomas (p <   0.05). IGFBP2 and IGFBP5 expression correlated with the expression status of progesterone receptor and HER-2/neu in the overall T1 carcinoma group, but no association was found with tumor size or the expression status of estrogen receptor. Our data suggest that IGFBP2 and IGFBP5 play a role in the development of metastasis and may serve as useful markers to predict lymph node metastasis in patients with small (T1) invasive breast carcinomas.  相似文献   

19.
The molecular subtypes of breast cancer based on status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) expression are associated with markedly different clinical outcomes. We retrospectively analyzed 774 breast cancer patients with four or more positive nodes, who underwent mastectomy between March 1999 and December 2007. Treatment with postmastectomy radiotherapy (PMRT) reduced the rates of locoregional recurrence-free survival (LRFS; 6.7% vs. 26.6%), distant metastasis-free survival (DMFS; 26.9% vs. 50.0%), and mortality (24.4% vs. 45.3%) for luminal-A subtypes (ER+ or PR+, Her2-) and reduced LRFS (12.1% vs. 27.5%) for the luminal-B subtype (ER+ or PR+, Her2+) compared with patients not receiving PMRT. However, PMRT did not affect the endpoints for the Her2-enriched or basal subtypes. Thus, understanding the differences in patterns of relapse between the different subtypes of breast cancer may enable targeted adjuvant therapy and improved surveillance decisions.  相似文献   

20.
BACKGROUND: Neoadjuvant chemotherapy may decrease tumor volume to allow breast conservation surgery. Its effect on estrogen and progesterone receptor (ER/PR) expression and hormone receptor (HR) status is controversial. METHODS: From February 2001 to July 2002, 56 breast cancer patients treated with neoadjuvant chemotherapy and 56 non-neoadjuvant therapy (control) patients with adequate tissue samples were identified. Quantitative ER/PR expression was analyzed in preneoadjuvant or preoperative core biopsies and final surgical specimens. Changes between the two groups were compared to determine if alterations were due to neoadjuvant chemotherapy or tissue sampling. RESULTS: The ER/PR expression changed in 34 (61%) neoadjuvant chemotherapy patients and 27 (48%) control patients. These expression changes resulted in HR status (positive/negative) alterations in 3 patients (5%) in both groups. Age, histology, chemotherapy regimen, and neoadjuvant response did not predict change. CONCLUSIONS: Hormone receptor status changed in 5% of neoadjuvant chemotherapy and control groups due to tissue sampling. As these changes may impact treatment, HR expression reanalysis in final surgical specimens is recommended.  相似文献   

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