Automated and ultrasensitive point-of-care glycoprotein detection using boronate-affinity enhanced organic electrochemical transistor patch.

Quantifying trace glycoproteins in biofluids requires ultrasensitive components, but feedback is not available in the current portable platforms of point-of-care (POC) diagnosis technologies. A compact and ultrasensitive bioelectrochemical patch was based on boronate-affinity amplified organic electrochemical transistors (BAAOECTs) for POC use was developed to overcome this dilemma. Benefit from the cascading signal enhancement deriving from boronate-affinity targeting multiple regions of glycoprotein and OECTs' inherent signal amplification capability, the BAAOECTs achieved a detection limit of 300 aM within 25 min, displaying about 3 orders of magnitude improvement in sensitivity compared with the commercial electrochemical luminescence (ECL) kit. By using a microfluidic chip, a microcontroller module, and a wireless sensing system, the testing workflows of the above patch was automated, allowing for running the sample-to-answer pipeline even in a resource-limited environment. The reliability of such portable biosensing platform is well recognized in clinical diagnostic applications of heart failure. Overall, the remarkable enhanced sensitivity and automated workflow of BAAOECTs biosensing platform provide a prospective and generalized design policy for expanding the POC diagnosis capabilities of glycoproteins.

Black Phosphorus Flake-Enabled Wireless Neuromodulation for Epilepsy Treatment.

Epilepsy is a prevalent and severe neurological disorder and generally requires prolonged electrode implantation and tether brain stimulation in refractory cases. However, implants may cause potential chronic immune inflammation and permanent tissue damage due to material property mismatches with soft brain tissue. Here, we demonstrated a nanomaterial-enabled near-infrared (NIR) neuromodulation approach to provide nongenetic and nonimplantable therapeutic benefits in epilepsy mouse models. Our study showed that crystal-exfoliated photothermal black phosphorus (BP) flakes could enhance neural activity by altering the membrane capacitive currents in hippocampus neurons through NIR photothermal neuromodulation. Optical stimulation facilitated by BP flakes in hippocampal slices evoked action potentials with a high spatiotemporal resolution. Furthermore, BP flake-enabled NIR neuromodulation of hippocampus neural circuits can suppress epileptic signals in epilepsy model mice with minimal invasiveness and high biocompatibility. Consequently, nanomaterial-enabled NIR neuromodulation may open up opportunities for nonimplantable optical therapy of epilepsy in nontransgenic organisms.

Transcranial Nongenetic Neuromodulation via Bioinspired Vesicle-Enabled Precise NIR-II Optical Stimulation.

Regulating the activity of specific neurons is essentially important in neurocircuit dissection and neuropathy therapy. As a recently developed strategy, nanomaterial-enabled nongenetic neuromodulations that realize remote physical stimuli have made vast progress and shown great clinical potential. However, minimal invasiveness and high spatiotemporal resolution are still challenging for nongenetic neuromodulation. Herein, a second near-infrared (NIR-II)-light-induced transcranial nongenetic neurostimulation via bioinspired nanovesicles is reported. The rationally designed vesicles are obtained from vesicle-membrane-confined enzymatic reactions. This study demonstrates that the vesicle-enabled NIR-II photothermal stimuli can elicit neuronal signaling dynamics with precise spatiotemporal control and thus evoke defined neural circuits in nontransgenic mice. Moreover, the vesicle-mediated NIR-II optical stimulation can regulate mouse motor behaviors with minimal invasiveness by eliminating light-emitting implants. Furthermore, the biological modulation is integrated with photoacoustic brain imaging, realizing navigational, and efficient neuromodulation. Such transcranial and precise NIR-II optical neuromodulation mediated by bioinspired vesicles shows the potential for the optical-theranostics of neurological diseases in nontransgenic organisms.

Wearable bioelectronic masks for wireless detection of respiratory infectious diseases by gaseous media.

Respiratory infectious diseases (H1N1, H5N1, COVID-19, etc.) are pandemics that can continually spread in the air through micro-droplets or aerosols. However, the detection of samples in gaseous media is hampered by the requirement for trace amounts and low concentrations. Here, we develop a wearable bioelectronic mask device integrated with ion-gated transistors. Based on the sensitive gating effect of ion gels, our aptamer-functionalized transistors can measure trace-level liquid samples (0.3 µL) and even gaseous media samples at an ultra-low concentration (0.1 fg/mL). The ion-gated transistor with multi-channel analysis can respond to multiple targets simultaneously within as fast as 10 min, especially without sample pretreatment. Integrating a wireless internet of things system enables the wearable mask to achieve real-time and on-site detection of the surrounding air, providing an alert before infection. The wearable bioelectronic masks hold promise to serve as an early warning system to prevent outbreaks of respiratory infectious diseases.

Multi-channel AgNWs-doped interdigitated organic electrochemical transistors enable sputum-based device towards noninvasive and portable diagnosis of lung cancer.

Biochemical monitoring of bodily fluidics such as sweat, urine, and tears have been extensively developed, but reliable biochemical analysis of sputum biospecimens remains limited and challenging due to the low abundance of biomarkers in intrinsically viscous sputum. We reported a portable multi-channel sputum-based interdigitated organic electrochemical transistors (SiOECTs) device for noninvasive sputum diagnosis. We tailored the AgNWs-doped organic electrochemical transistors, integrating with multiplexed aptamer-antigen assays, to realize the signal amplification and simultaneous detection of biomarkers in raw sputum biospecimens from lung cancer patients. Clinical validation studies demonstrated favorable correlation coefficients between the sputum and serum biospecimens. By utilizing our portable multi-channel iOECTs devices, lung cancer patients were differentiated from health control with an optimum area under the curve (AUC) of 0.931, sensitivity of 87.0%, and specificity of 86.5%. Our miniaturized and portable device could even realize the continuous in-home tracking of the biomarkers change for lung cancer patients after radiotherapy/chemotherapy. It is envisaged that the SiOECTs will shed light on noninvasive diagnostics platforms for sputum-related diseases.

Prevalence and risk factors of lens opacities in rural populations living at two different altitudes in China.

AIM: To investigate the prevalence of and risk factors for lens opacities in populations living at two different altitudes in China. METHODS: A total of 813 subjects aged ≥40y in Lhasa (Tibet Autonomous Region, China. Altitude: 3658 m) and Shaoxing (Zhejiang Province, China. Altitude: 15 m) were underwent eye examinations and interviewed in this cross-sectional study. Participants' lens opacities were graded according to the Lens Opacities Classification System II (LOCS II) and the types of opacities with LOCS II scores ≥2 were determined. Univariate and stepwise logistic regression were used to evaluate the associations of independent risk factors with lens opacities. RESULTS: Lens opacities were significantly more prevalent in the high-altitude than in the low-altitude area (χ (2)=10.54, P<0.001). Lens opacities appear to develop earlier in people living at high than at low altitude. The main types of lens opacity in Lhasa and Shaoxing were mixed (23.81%) and cortical (17.87%), respectively. Independent risk factors associated with all lens opacities were age, ultraviolet (UV) radiation exposure, and educational level. Compared with participants aged 40-49y, the risk of lens opacities increased gradually from 2 to 85 times per 10y [odds ratio (OR)=2.168-84.731, P<0.05). The risk of lens opacities was about two times greater in participants with the highest UV exposure than in those with the lowest exposure (OR=2.606, P=0.001). Educational level was inversely associated with lens opacities; literacy deceased the risk by about 25% compared with illiteracy (OR=0.758, P=0.041). CONCLUSION: Old age, higher UV exposure and lower educational level are important risk factors for the development of lens opacities. Lens opacities are more prevalent among high-altitude than low-altitude inhabitants.

A new model for predicting non-sentinel lymph node status in Chinese sentinel lymph node positive breast cancer patients.

BACKGROUND: Our goal is to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Stanford Online Calculator (SOC) for predicting non-sentinel lymph node (NSLN) metastasis in Chinese patients, and develop a new model for better prediction of NSLN metastasis. METHODS: The MSKCC nomogram and SOC were used to calculate the probability of NSLN metastasis in 120 breast cancer patients. Univariate and multivariate analyses were performed to evaluate the relationship between NSLN metastasis and clinicopathologic factors, using the medical records of the first 80 breast cancer patients. A new model predicting NSLN metastasis was developed from the 80 patients. RESULTS: The MSKCC and SOC predicted NSLN metastasis in a series of 120 patients with an area under the receiver operating characteristic curve (AUC) of 0.688 and 0.734, respectively. For predicted probability cut-off points of 10%, the false-negative (FN) rates of MSKCC and SOC were both 4.4%, and the negative predictive value (NPV) 75.0% and 90.0%, respectively. Tumor size, Kiss-1 expression in positive SLN and size of SLN metastasis were independently associated with NSLN metastasis (p<0.05). A new model (Peking University People's Hospital, PKUPH) was developed using these three variables. The MSKCC, SOC and PKUPH predicted NSLN metastasis in the second 40 patients from the 120 patients with an AUC of 0.624, 0.679 and 0.795, respectively. CONCLUSION: MSKCC nomogram and SOC did not perform as well as their original researches in Chinese patients. As a new predictor, Kiss-1 expression in positive SLN correlated independently with NSLN metastasis strongly. PKUPH model achieved higher accuracy than MSKCC and SOC in predicting NSLN metastasis in Chinese patients.

Multicenter prospective study of magnetic resonance imaging prior to breast-conserving surgery for breast cancer.

BACKGROUND: This multicenter prospective study aimed to assess the utility of dynamic enhanced magnetic resonance imaging (MRI) prior to breast-conserving surgery for breast cancer. METHODS: The research subjects were drawn from patients with primary early resectable breast cancer treated in the breast disease centers of six three-level hospitals in Beijing from 1 January 2010 to 31 December 2012. The participants were allocated to a breast-conserving surgery group (breast-conserving group) or a total mastectomy group (total mastectomy group). Enhanced MRI was used to measure breast volume, longest diameter of tumor and tumor volume. The correlations between these measurements and those derived from histopathologic findings were assessed. The relationships between the success rate of breast-conserving surgery and MRI- and pathology-based measurement results were statistically analyzed in the breast-conserving group. RESULTS: The study included 461 cases in the total mastectomy group and 195 in the breast-conserving group. Allocation to these groups was based on clinical indications and patient preferences. The cut-off for concurrence between MRI- and pathology-based measurements of the longest diameter of tumor was set at 0.3 cm. In the total mastectomy group, the confidence interval for 95% concurrence of these measurements was 35.41%-44.63%. Correlation coefficients for MRI and histopathology-based measurements of breast volume, tumor volume and tumor volume/breast volume ratio were r = 0.861, 0.569, and 0.600, respectively (all P < 0.001). In the breast-conserving group, with 0.30 cm taken as the cut-off for concurrence, the 95% confidence interval for MRI and pathology-based measurements of the longest diameter of tumor was 29.98%-44.01%. The subjective and objective success rates for breast-conserving surgery were 100% and 88.54%, respectively. CONCLUSIONS: There were significant correlations between dynamic enhanced MRI- and histopathology-based measurements of the longest diameter of breast lesions, breast and tumor volumes, and breast volume/tumor volume ratios. Preoperative MRI examination improves the success rate of breast-conserving surgery.

[Analysis of intraoperative molecular assessment of sentinel lymph nodes in breast carcinoma].

OBJECTIVE: To evaluate the reliability and application of GeneSearch(TM) breast lymph node assay (Genesearch), a real-time fluorescence quatitative PCR method, in intraoperative assay of metastasis in sentinel lymph nodes (SLNs) from breast cancer patients. METHODS: Totally 140 SLNs from 80 patients with breast carcinoma were prospectively studied from May 2010 to August 2010. The 80 patients included 78 women and 2 men who ranged in age from 29 to 85 years, and the median age is 49 years. The expression of CK19 and mammaglobulin in all 140 SLNs were detected by Genesearch, and the results were compared with that of histological evaluation of both frozen and paraffin-embedded sections. RESULTS: Among SLNs, by histological analyses, there were 121 without metastasis, 17 with macrometastasis, 2 with micrometastasis, and none of isolated tumor cell. By Genesearch, there were 119 without metastasis and 21 with metastasis. Genesearch showed sensitivity of 89.4%, positive predictive value of 81.0%, negative predictive value of 98.3% and specificity of 96.7% by comparing to histological analyses. The concordance between Genesearch and histological analysis was 95.7%. The sensitivity of Genesearch was 15/17 for macrometastasis and 2/2 for micrometastasis. CONCLUSIONS: Genesearch detection presents high sensitivity and specificity in evaluating metastasis of sentinel lymph nodes in breast cancer, but strict performance technically is necessary to avoid false positive and false negative results. Inability of further subtyping for the positive cases might be the key limitations for wide application of this method.

A logistic regression model for predicting axillary lymph node metastases in early breast carcinoma patients.

Nodal staging in breast cancer is a key predictor of prognosis. This paper presents the results of potential clinicopathological predictors of axillary lymph node involvement and develops an efficient prediction model to assist in predicting axillary lymph node metastases. Seventy patients with primary early breast cancer who underwent axillary dissection were evaluated. Univariate and multivariate logistic regression were performed to evaluate the association between clinicopathological factors and lymph node metastatic status. A logistic regression predictive model was built from 50 randomly selected patients; the model was also applied to the remaining 20 patients to assess its validity. Univariate analysis showed a significant relationship between lymph node involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression. Absence of Kiss-1 remained significantly associated with positive axillary node status in the multivariate analysis (p = 0.018). Seven clinicopathological factors were involved in the multivariate logistic regression model: menopausal status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.702 when applied to the validation group. Moreover, there is a need discover more specific candidate proteins and molecular biology tools to select more variables which should improve predictive accuracy.

[Comparison of dynamic optical breast imaging (DOBI) and mammography in sensitivity, specificity and safety of breast cancer diagnosis: a prospective analysis of 62 patients in two centers].

OBJECTIVE: To assess the sensitivity, specificity and safety of dynamic optical breast imaging (DOBI) and mammography according to the pathological results. METHODS: From June 2005 to January 2006, 62 patients in Peking University People's Hospital and Capital Medical University Affiliated ChaoYang Hospital who received mammography and needed biopsy were enrolled prospectively, signed the consent form and recorded the comfortable level, acceptability and any complications during DOBI examination. Images obtained with DOBI and mammography were evaluated by 3 independent doctors who didn't know the pathological results to calculate the breast cancer diagnostic sensitivity and specificity. RESULTS: In this study the sensitivity and specificity of breast cancer diagnosis by mammography were 0.935 5±0.044 1 (95%CI 0.709 2-0.968 2)and 0.451 6±0.089 4 (95%CI 0.276 4-0.626 8)respectively. The sensitivity and specificity of DOBI were 0.838 7±0.066 1 (95%CI 0.709 2-0.968 2)and 0.612 9±0.087 5 (95%CI 0.441 4-0.784 4)respectively. In the DOBI examination there was no adverse reaction. The tolerability of DOBI was good. CONCLUSION: Dynamic optical breast imaging could provide the functional information about angiogenesis on the lesion and improve the breast cancer diagnostic specificity. It is a potential non-invasive breast functional imaging diagnostic tool and needs more large scale clinical trial to determine its indications and diagnostic criteria.

Response to neoadjuvant therapy and disease free survival in patients with triple-negative breast cancer.

BACKGROUND: Triple negative breast cancer(TNBC)is characterized by estrogen receptor (ER) negative, progesterone receptor (PgR)negative and human epidermal growth factor receptor 2 (HER-2) negative. It is a high risk breast cancer that lacks the benefit of specific therapy targeting these proteins. In this study, we compared the response to neoadjuvant chemotherapy and disease free survival between patients with TNBC and non-TNBC. METHODS: 151 patients were included in this study, who received neoadjuvant taxane and anthracycline-based chemotherapy at Peking University People's Hospital from 2002 to 2007. TNBC is defined by the lack of ER, PgR, and HER-2 expression by immunohistochemistry. Clinical and pathologic parameters, pathologic complete response(pCR)rates and survival measurements were compared between patients with TNBC and non-TNBC. RESULTS: 21 of 151 patients (14%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates(38% v 12%; p=0.002), but decreased disease-free survival rates(p=0.004). If pCR was achieved, patients with TNBC and non-TNBC had similar survival (p=0.497). CONCLUSIONS: Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR achieved excellent disease free survival. However, patients who did not get pCR have significantly worse survival if they have TNBC compared with non-TNBC.

Biological markers as predictive factors of response to neoadjuvant taxanes and anthracycline chemotherapy in breast carcinoma.

BACKGROUND: Neoadjuvant chemotherapy provides an excellent model for evaluation of potential predictive factors. The objective of this study was to evaluate the predictive value of different biological factors in breast cancer patients treated with neoadjuvant taxane and anthracycline chemotherapy. METHODS: One hundred and thirty-five patients treated with 4 cycles of neoadjuvant taxanes and anthracycline were included in this retrospective study. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PgR), HER-2, Ki-67 and p53 protein expression. The associations among biological markers and clinical and pathological complete response (pCR) were analyzed. RESULTS: The overall clinical response was 86%, including 33% clinical complete response (cCR) and 53% clinical partial response. The pCR was just 17%. In the univariate analysis, only HER-2 overexpression was predictive of cCR to neoadjuvant chemotherapy (P=0.018). No significant associations between other biological factors and cCR were found. Absence of ER, PgR expression and overexpression of HER-2 were predictive of the pCR (P=0.002, 0.001, 0.01, respectively). Ki-67 and p53 failed to show an association with pCR. In multivariate analysis, overexpression of HER-2 remained as an independent variable in predicting the cCR (P=0.021). However, negative ER was the only parameter that maintained statistical significance in predicting the pCR (P=0.001). CONCLUSIONS: Patients with overexpression of HER-2 and negative hormonal receptor status are much more likely to respond to neoadjuvant taxane and anthracycline chemotherapy than those with the opposite characteristics. These factors could serve as predictive markers for this regimen.

[Effect of neoadjuvant chemotherapy on estrogen and progesterone receptors and P53 and CerbB-2 in breast cancer].

OBJECTIVE: To study the effect to neoadjuvant chemotherapy on estrogen receptor (ER), progesterone receptor (PR), P53 and CerbB-2 expression in patients with breast cancer. METHODS: From 123 breast cancer patients treated with neoadjuvant chemotherapy, core needle biopsy samples before the chemotherapy and surgical specimens were obtained for assay of ER, PR, P53 and CerbB-2 expression. RESULTS: ER expression occurred in 46.61% (55/118) of the patients before neoadjuvant chemotherapy and in 66.10% (78/118) of these after surgery showing statistically significant. But the changes in PR, P53 and CerbB-2 expression exhibited no significant difference. CONCLUSIONS: Significant changes occur in ER expression after neoadjuvant chemotherapy in patients with breast cancer. Neoadjuvant chemotherapy has no significant effects on PR, P53 and CerbB-2 expression in patients with breast cancer.

[Side effects of adjuvant chemotherapy and radiotherapy concurrently after conservative surgery for breast cancer].

OBJECTIVE: Observe the side effects of adjuvant chemotherapy and radiotherapy concurrently after breast conservative surgery and investigate it feasible. METHODS: 40 breast cancer patients of conservative surgery were divided into two groups randomizedly, 20 patients of the study group were given adjuvant chemotherapy and radiotherapy concurrently, 20 patients of the control group were given adjuvant thermotherapy and radiotherapy sequently. Observe the side effects of the patients in the two groups and follow them 6 months. RESULTS: The leukopenia within the third chemotherapeutic cycle and the oral mucitis within the fourth chemotherapeutic cycle in the study group were more severe than those in the control group (P < 0.05). The other side effects within every chemotherapeutic cycles were similar in both groups, including skin reaction in radiotherapeutic area, gastroenteric reaction, alopecia, arthralgia, neurotoxicity and abnormal hepatic function. Following the patients of the two groups in 6 months, there were no significance in hemogram, hepatic and renal function, electrocardiogram and chest x-ray. CONCLUSION: It is feasible and safe to give the adjuvant chemotherapy and radiotherapy concurrently to the breast cancer patients after conservative surgery.

[The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression in breast carcinoma].

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on estrogen receptor (ER) and progesterone receptor (PR) expression in breast carcinoma. METHODS: Samples were obtained from 31 patients with breast carcinoma who received neo-adjuvant chemotherapy, ER or PR expressions were analyzed in preoperative core biopsies and final surgical specimens. RESULTS: ER level was up-regulated in 13 (41.9%) out of 31 cases, PR level was up-regulated in 10 (32.3%). Both ER level and PR level were up-regulated in 8 (25.8%) out of 31 cases. CONCLUSIONS: Neoadjuvant chemotherapy may impact the hormone receptor status, ER and PR expression re-analysis in final surgical specimens is recommended.

[Feasibility of breast conservation surgery after neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the efficacy of neoadjuvant chemotherapy (NCT) and the feasibility of conservative breast surgery after reducing the size of a primary tumor by NCT in patients with operable breast cancer. METHODS: Thirty patients with stage IIB and IIIA breast cancer underwent NCT including epirubicin 60 mg/m(2) by intravenous injection on day 1 and paclitaxel 150 mg/m(2) by 3-hour continuous infusion on day 2 with 21 days as a cycle from July 2001 to April 2003. All patients received 3 - 4 cycles of NCT. Breast conservation treatment or modified mastectomy was performed after the tumor was reduced to less than 3 cm in diameter. The nonresponders received modified mastectomy. RESULTS: The overall response rate (ORR) was 93% (28/30) for the primary tumors of breast, Fifteen patients (50%) obtained clinical complete response (cCR), including 7 cases (23%) with pathologic complete response (pCR). Thirteen cases (43%) achieved clinical partial response (cPR), and 2 (7%) no change (NC). No case showed progression of disease. Twenty-six (87%) cases were downstaged according to the TNM system classification. The median initial tumor size was 4 cm (3 - 10 cm) before NCT and was reduced to 0.8 cm (0 - 6 cm) after NCT. All 30 patients received operation. Eighteen (60%) of them were candidates for breast conserving therapy, and actually only 11 (37%) selected such surgery. CONCLUSION: An effective treatment for operable breast cancer, NCT with epirubicin plus paclitaxel results in significant downstaging or eliminating of primary tumors in breast cancer, thus expanding the indication of breast conservation therapy.

[The effect of transfecting Stat3beta cDNA on human breast cancer].

OBJECTIVE: To study the effect of transfecting Stat3beta cDNA on human breast cancer. METHODS: Human breast cancer cells of the line SK-BR-3 were cultured and divided into 3 groups: Stat3beta transfection group (to be transfected with plasmid pIRES-Stat3beta containing Stat3beta by transient transfection technique), lipofectin reagent transfection group pIRES-EGFP transfection group, and control group. The positively transfected cells were isolated by fluorescence-activated cell sorter. Flow cytometry was used to analyze the cell cycles and cell apotosis. Western blotting was used to detect the expression of STAT3 protein. MTT method was used to examine the proliferation of the cells. RESULTS: Forty-eight hours after exposure to the plasmid pIRES-Stat3beta the transfection rate of the SK-BR-3 cells was 13.79%. SK-BR-3 cells expressed STA3 protein during proliferation. In comparison with the SK-BR-3 cells of other 3 group, the proliferation of the cells transfected with pIRES-Stat3beta was significantly decreased. Forty-eight hours after transfection, 81.09% of the cells transfected with the plasmid pIRES-Stat3beta accumulated at the G(0)/G(1) stage, a rate significantly higher than those of the other groups, and displayed a significantly higher rate of apoptosis. CONCLUSION: Transfection of plasmid pIRES-Stat3beta containing Stat3beta blocks the Stat3 pathway, thus inhibiting the proliferation and augment the apoptosis of human breast cancer cells and providing a novel gene therapy target.

[Expression and significance of estrogen receptor isoforms in the development of human breast carcinoma].

OBJECTIVE: To investigate the estrogen receptors (ER)alpha and ERbeta expression and their relationship with clinicopathological parameters in human breast carcinoma. METHODS: Samples were obtained from 30 breast carcinoma, reverse transcriptase polymerase chain reaction was used to measure the expression of ERalpha and ERbeta mRNA. RESULTS: ERalpha mRNA level was up-regulated in breast carcinoma tissue compared with adjacent normal tissue (t = 7.399, P < 0.01) while down-regulated in ERbeta. The relative ratio of ERalpha and ERbeta was decreased in normal tissue vs. carcinoma (t = 6.385, P < 0.01), in patients with lymph node metastasis vs. those without lymph node metastasis (t = 2.602, P < 0.05), in late stage carcinoma vs. early stage (t = 3.754, P < 0.05). CONCLUSION: ERalpha and ERbeta play divergent role in the development of human breast carcinoma.