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Objective: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. Methods: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. Results: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. Conclusion: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this paper was to clarify the optimal minimum number of lymph node for CEA-elevated (≥ 5 ng/ml) colon cancer patients. Methods: Thirteen thousand two hundred thirty-nine patients from the SEER database and 238 patients from the Second Affiliated Hospital of Harbin Medical University (External set) were identified. For cancer-specific survival (CSS), Kaplan-Meier curves were drawn and data were analyzed using log-rank test. Using X-tile software, the optimal cut-off lymph node count was calculated by the maximal Chi-square value method. Cox regression model was applied to perform survival analysis. Results: In CEA-elevated colon cancer, 18 nodes were defined as the optimal minimum node. The number of lymph node examined (< 12, 12-17 and ≥ 18) was an independent prognosticator in both SEER set (HR12-17 nodes = 1.329, P < 0.001; HR< 12 nodes = 1.985, P < 0.001) and External set (HR12-17 nodes = 1.774, P < 0.032; HR< 12 nodes = 2.741, P < 0.006). Moreover, the revised 18-node standard could identify more positive lymph nodes compared with the 12-node standard in this population. Conclusions: With the purpose of favorable long-term survival and accurate nodal stage for CEA-elevated colon cancer patients, the 18-node standard could be regarded as an alternative to the 12-node standard advocated by the ASCO and NCCN guidelines. [ABSTRACT FROM AUTHOR]

Long intergenic non-coding RNA 00852 (LINC00852) has been shown to promote the progression of many different cancers including prostate cancer. However, the involved mechanism in promoting the proliferation, migration and invasion of prostate cancer cells has not been reported. In this study, we found that LINC00852 was highly expressed in the tissue of prostate cancer using quantitative reverse transcription PCR (qRT-PCR). CCK-8 assay, colony formation experiment, Transwell migration and invasion experiments were performed to prove that the up-regulation of LINC00852 could promote the proliferation, migration and invasion of prostate cancer cells in vitro. Xenograft tumors experiments in nude mice confirmed that up-regulation of LINC00852 promoted the proliferation of prostate cancer cells in vivo. Bioinformatics predictions and dual-luciferase reporter gene assay showed that miR-29a-3p binds to the 3'-untranslated region of JARID2, and the enhancement of miR-29a-3p could reverse the effect of LINC00852 overexpression in vitro. Moreover, the results of qRT-PCR and western blot showed that LINC00852 could regulate the expression of JARID2 through miR-29a-3p induction. In summary, we demonstrated that LINC00852 played a key role in promoting the prostate cancer, and LINC00852/miR-29a-3p/JARID2 axis could be used as a target for prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the efficiency and safety of the new generation antibody-drug conjugate Trastuzumab deruxtecan (DS-8201a) in treating HER2-positive solid cancers.Method: By searching PubMed, Medline and Ovid for all clinical trials related to the safety and efficacy of DS-8201a. Event rates were calculated for all adverse events (AEs) to evaluate the safety of DS-8201a. Objective response rate (ORR) and progression-free survival (PFS) were summarized to assess the potency of DS-8201a.Result: The AEs with event rates greater than 30% regardless of grades were nausea, decreased appetite, vomiting, fatigue, anemia, decreased neutrophil count, alopecia and diarrhea. In the grade 3 or more, decreased neutrophil count, anemia and decreased white blood cell count were the only three AEs with event rates greater than 10% (20.3, 15.0 and 10.3%). The median PFS of patients with breast cancer, gastric cancer and other HER2-positive solid cancers were 9.0-22.1, 3.0-8.3 and 4.1-11.9 months. The median ORR was 37-79.9% in patients with breast and gastric cancer and 28.3-55% in patients with other HER2-positive cancers.Conclusion: DS-8201a plays an active role in treating HER2-positive cancers, especially breast and gastric cancer, which have HER2 amplification. The most common AEs of DS-8201a were related to gastrointestinal and hematological system. Decreased white blood cell count and appetite were the AEs occurred with high grades. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of different adjuvant therapy on IB1 and IIA1 stage cervical squamous cell cancer patients with lymphovascular space invasion. It also aimed to analyze the relationship between lymphovascular space invasion and other clinical pathological characteristics on IB1 and IIA1 stage cervical squamous cell cancer patients.Methods: This retrospective observational study collected data of FIGO stages IB1 and IIA1 squamous cervical cancer patients at the First Affiliated Hospital of Chongqing Medical University between 2014 and 2018. A correlation analysis between lymphovascular space invasion and other clinical or pathological factors was conducted. Prognosis analysis of patients with lymphovascular space invasion were performed to assess associations between clinical-pathological characteristics and survival.Results: A total of 357 women were identified including 110 (30.8%) with lymphovascular space invasion, 247 (69.2%) without lymphovascular space invasion. Both middle 1/3 cervical stromal invasion (p = 0.000) and deep 1/3 cervical stromal invasion (p = 0.000) were independently associated with lymphovascular space invasion. Among lymphovascular space involved women, tumor differentiation (P = 0.001) and postoperative therapy (P = 0.036) had a significant influence on disease recurrence. Multivariate analysis showed that lymph node metastasis (P = 0.017), poorer tumor differentiation (P = 0.036) and postoperative chemotherapy alone (P = 0.021) can increase the risk of tumor relapse.Conclusion: Our study suggested that the presence of deep stromal invasion independently increases the risk of lymphovascular space invasion. Compared with chemotherapy, chemoradiotherapy seems to improve progression-free survival in squamous cervical cancer patients with lymphovascular space invasion. [ABSTRACT FROM AUTHOR]

Background: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC.Methods: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population.Results: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE.Conclusions: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1. [ABSTRACT FROM AUTHOR]

Background: The fragility index (FI) of trial results can provide a measure of confidence in the positive effects reported in randomized controlled trials (RCTs). The aim of this study was to calculate the FI of RCTs supporting HCC treatments.Methods: A methodological systematic review of RCTs in HCC treatments was conducted. Two-arm studies with randomized and positive results for a time-to-event outcome were eligible for the FI calculation.Results: A total of 6 trails were included in this analysis. The median FI was 0.5 (IQR 0-10). FI was ≤7 in 4 (66.7%) of 6 trials; in those trials the fragility quotient was ≤1%.Conclusion: Many phase 3 RCTs supporting HCC treatments have a low FI, which challenges the confidence in concluding the superiority of these drugs over control treatments. [ABSTRACT FROM AUTHOR]

Purpose: Significant advancements in improving ovarian cancer (OC) outcomes have been limited over the past decade. To predict prognosis and improve outcomes of OC, we plan to develop and validate a robust prognosis signature based on blood features. Methods: We screened age and 33 blood features from 331 OC patients. Using ten machine learning algorithms, 88 combinations were generated, from which one was selected to construct a blood risk score (BRS) according to the highest C-index in the test dataset. Results: Stepcox (both) and Enet (alpha = 0.7) performed the best in the test dataset with a C-index of 0.711. Meanwhile, the low RBS group possessed observably prolonged survival in this model. Compared to traditional prognostic-related features such as age, stage, grade, and CA125, our combined model had the highest AUC values at 3, 5, and 7 years. According to the results of the model, BRS can provide accurate predictions of OC prognosis. BRS was also capable of identifying various prognostic stratifications in different stages and grades. Importantly, developing the nomogram may improve performance by combining BRS and stage. Conclusion: This study provides a valuable combined machine-learning model that can be used for predicting the individualized prognosis of OC patients. [ABSTRACT FROM AUTHOR]

Background: Texture analysis of medical images has been reported to be a reliable method for differential diagnosis of neoplasms. This study was to investigate the performance of textural features and the combined performance of textural features and morphological characteristics in the differential diagnosis of pancreatic serous and mucinous cystadenomas.Methods: We retrospectively reviewed 59 patients with pancreatic serous cystadenoma and 32 patients with pancreatic mucinous cystadenoma at our hospital. A three-dimensional region of interest (ROI) around the margin of the lesion was drawn manually in the CT images of each patient, and textural parameters were retrieved from the ROI. Textural features were extracted using the LifeX software. The least absolute shrinkage and selection operator (LASSO) method was applied to select the textural features. The differential diagnostic capabilities of morphological features, textural features, and their combination were evaluated using receiver operating characteristic (ROC) analysis, and the area under the receiver operating characteristic curve (AUC) was used as the main indicator. The diagnostic accuracy based on the AUC value is defined as follows: 0.9-1.0, excellent; 0.8-0.9, good; 0.7-0.8, moderate; 0.6-0.7, fair; 0.5-0.6, poor.Results: In the differential diagnosis of pancreatic serous and mucinous cystadenomas, the combination of morphological characteristics and textural features (AUC 0.893, 95% CI 0.816-0.970) is better than morphological characteristics (AUC 0.783, 95% CI 0.665-0.900) or textural features (AUC 0.777, 95% CI 0.673-0.880) alone.Conclusions: In conclusion, our preliminary results highlighted the potential of CT texture analysis in discriminating pancreatic serous cystadenoma from mucinous cystadenoma. Furthermore, the combination of morphological characteristics and textural features can significantly improve the diagnostic performance, which may provide a reliable method for selecting patients with surgical intervention indications in consideration of the different treatment principles of the two diseases. [ABSTRACT FROM AUTHOR]

Background: Certain markers have been identified over the last 10 years that facilitate the prediction of a patient's prognosis; these markers have been proposed to be useful for risk stratification of lymphoma patients and for the development of specific therapeutic strategies. In the present study, we assessed the potential prognostic value of SPRR1A expression in 967 patients with diffuse large B-cell lymphomas.Methods: All patients were enrolled between 2001 and 2007 (median follow-up, 53.3 months) in the Second Hospital of Dalian Medical University, First Hospital of China Medical University, and Liaoning Cancer Hospital. Immunohistochemical analysis was used to evaluate the expression of SPRR1A. Survival was analyzed using the Kaplan-Meier method. Multivariate analysis was conducted to adjust the effect of SPRR1A expression for potential, well-known, independent prognostic factors.Results: Of the 967 patients examined, SPRR1A expression was detected in 305 (31.54%) patients on immunohistochemical analysis. The 5-year survival rate was significantly lower in patients with SPRR1A expression than in those without (26.9% vs. 53.2%, P < 0.001). Multivariate analysis identified SPRR1A expression as an independent predictor of survival in addition to lactate dehydrogenase level, clinical stage, and histologic subtype.Conclusions: SPRR1A expression may be useful as a prognostic factor for diffuse large B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Background: Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC).Methods and Materials: EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues, a normal liver cell line and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were correlated with expression of EGFL8. Subsequently, the gain-and loss-of-function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)- phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory.Results: The expression of EGFL8 was significantly decreased in HCC tissues and cell lines and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment.Conclusion: The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC. [ABSTRACT FROM AUTHOR]

Background: Advances in oncology led to a substantial increase in the number of patients requiring admission to the ICU. It is significant to confirm which cancer critical patients can benefit from the ICU care like noncancer patients.Methods: An observational retrospective cohort study using intensive care unit (ICU) admissions of Medical Information Mart for Intensive Care III from the Beth Israel Deaconess Medical Center in Boston, MA, USA between 2001 and 2012 was conducted. Propensity score matching was used to reduce the imbalance between two matched cohorts. ICU patients with cancer were compared with those without cancer in terms of patients' characteristics and survival.Results: There were 38,508 adult patients admitted to ICUs during the period. The median age was 65 years (IQR, 52-77) and 8308 (21.6%) had an underlying malignancy diagnosis. The noncancer group had a significant survive advantage at the point of 28-day, 90-day, 365-day and 1095-day after ICU admission compared with cancer group (P < 0.001 for all) after PSM. Subgroup analysis showed that the diagnosis of malignancy didn't decrease 28-day and 90-day survive when patients' age ≥ 65-year, patients in surgical intensive care unit or cardiac surgery recovery unit or traumatic surgical intensive care unit, elective admissions, patients with renal replacement therapy or vasopressor support (P > 0.05 for all).Conclusions: Malignancy is a common diagnosis among ICU patients. Patients without cancer have a survive advantage compared with patients with cancer in the short- and medium-term. However, in selected groups, cancer critical patients can benefit from the ICU care service like noncancer patients in the short-term. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with progressive or recurrent high-grade gliomas (HGGs) after surgery remains poor. Iodine-125 brachytherapy is emerging as a salvage method for the treatment of gliomas. This study aimed to investigate whether permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection.Methods: Between March 2004 and August 2016, 58 patients with progressive or recurrent HGG after gross total resection were included in this study. Twenty-nine patients underwent radiotherapy and/or chemotherapy and then permanent iodine-125 brachytherapy (SRCI group). Twenty-nine patients underwent permanent iodine-125 brachytherapy alone (SI group). Follow-up was carried out at 1, 3, and 6 months and then at 1, 2, 3, and 5 years after iodine-125 implantation. The median overall survival (OS) and progression-free survival (PFS), procedure-related complications and clinical outcomes were evaluated.Results: No procedure-related fatal events happened. The temporary morbidity rate was 11.9%. The median OS and PFS for patients in the SI group were 22 and 8 months compared with 21 and 7 months in the SRCI group. No significant differences were found. Age and Karnofsky Performance Status (KPS) were independent prognostic factors for OS. Age, KPS and histology were independent prognostic factors for PFS.Conclusions: Permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection. [ABSTRACT FROM AUTHOR]

Background: Cancer patients' survival time has obviously improved, with the development of systemic treatment techniques. However, the probability of metastases to the vertebrae has also been increased which makes some adverse effects on patients' quality of life. The prediction of survival plays a key role in choosing therapeutic modality, and Tokuhashi Score was established as one of the most commonly used predictive systems for spinal metastases. Thus, this study was conducted to identify the prognostic effect of factors involved in revised Tokuhashi Score (RTS).Methods: Two investigators independently retrieved relevant literature on platforms of PubMed, Embase and Cochrane Library. We identified eligible studies through title/abstract and full-text perusing. Data was extracted including general information of studies, participants' characteristics, therapeutic modality, overall survival and prognostic effect of factors. Hazard ratio (HR) for each factor was synthesized if available through fixed- or random-effect models as appropriate.Results: A total of 63 eligible studies with 10,411 participants were identified. Overall, cases with thyroid cancer had the highest survival rate, while the ones with non-small cell lung cancer and hepatocellular carcinoma lived for the shorted survival time. Performance status, bone metastasis, number of involved vertebrae, visceral metastasis, primary tumor and neurological status were regarded as significant predictors in 71.4, 40.0, 18.2, 63.4, 73.1 and 44.7% of the involved studies respectively. Thirty-eight articles were included in meta-analysis, and prognostic effects of five factors (apart from primary tumor) were analyzed. Factors were all proved to be significant except comparisons between KPS (Karnofsky Performance Status) 10-40 VS. 50-70 and single VS. multiple spinal metastases.Conclusion: All factors of RTS were significant on prognosis predicting and should be considered when choosing therapeutic modality for spinal metastases. What's more, we believe that more accurate prognosis may be obtained after removal of the cut-offs for KPS 10-40 VS. 50-70 and single VS. multiple involved vertebrae. [ABSTRACT FROM AUTHOR]

Background: The Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification is a key gastric cancer prognosis system. This study aimed to create a new TNM system to provide a reference for the clinical diagnosis and treatment of gastric cancer.Methods: A review of gastric cancer patients' records was conducted in The First Hospital of China Medical University and the Liaoning Cancer Hospital and Institute. Based on patients' prognoses data, computer-aided unsupervised clustering was performed for all possible TNM staging situations to create a new staging division system.Results: The primary outcome measure was 5-year survival, analyzed according to TNM classifications. Computer-aided unsupervised clustering for all TNM staging situations was used to create TNM division criteria that were more consistent with clinical situations. Furthermore, unsupervised clustering for the number of lymph node metastasis in the N stage led to the formulation of a classification method that differs from the existing N stage criteria, and unsupervised clustering for tumor size provided an additional reference for prognosis estimates.Conclusions: Finally, we developed a TNM staging system based on the computer-aided unsupervised clustering method; this system was more in line with clinical prognosis data when compared with the 7th edition of UICC gastric cancer TNM classification. [ABSTRACT FROM AUTHOR]

Background: Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it's stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients.Methods: We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients.Results: In three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R 2 = 0.688, p < 0.001), additionally, plasma D-dimer represent a better survival predictor than CTCs.Conclusions: Plasma D-dimer is an essential accompaniment of CTCs in GC that is easy to measure and lower in cost, and can be used in the detection of hematogenous metastasis. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: The risk of lymph node positivity in early-stage colon cancer is a parameter that impacts therapeutic recommendations. However, little is known about the effect of age on lymph node positivity in colon cancer with mucosal invasion. In this study, we aimed to quantify the effect of younger age on lymph node positivity in colon cancer with mucosal invasion.Methods: All patients were identified between 2004 and 2014 in the Surveillance, Epidemiology, and End Results database. Patients were stage T1-T2, did not undergo preoperative radiotherapy, had at least one lymph node examined, and underwent a standard colon cancer operation. Demographics and pathological data were compared between different age ranges. A nomogram model was built to estimate the probability of nodal involvement according to different characteristics. Decision curve analysis was performed by calculating the net benefits for a range of threshold probabilities.Results: This study identified 41,490 patients who met the eligibility criteria for our study. 1.4% (n = 620) of patients were under 40 years old; 5.9% (n = 2571) were between 40 and 49 years old. Within each T stage, positive lymph node rates decreased with increasing age. In univariate analyses, the positive lymph node rates for patients 20 to 39 years of age were significantly higher than in patients in the reference group for stages T1 and T2. After dividing the colon into the left and right parts, these trends remained. The lymph node metastatic rate was higher in the right colon than in the left colon in terms of different age ranges. The nomogram prediction system represents a novel model with which to estimate lymph node metastasis in early T stage colon adenocarcinomas based on four risk factors with a C-index of 0.657 (95% CI: 0.658-0666).Conclusions: Our study demonstrates that the risk of lymph node metastasis was higher in young (< 40 years) patients with early-stage colon adenocarcinomas. Therefore, more aggressive screening and therapeutic strategies should be considered for young patients with colon adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance.Methods: Immunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n =89) and nodular thyroid goiter (NTG; n =30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed.Results: The positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18-45 years old; n =50) than age-matched female NTG patients (n =30), while ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n =39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERβ1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases.Conclusions: The differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful immunohistochemical marker for differential diagnosis of PTC. The associations of ER subtype expression with Ki-67, mutant P53, VEGF expression and ETE in female PTC patients of reproductive age suggest that estrogen-activated ERα may mediate stimulatory effects on PTC growth and progression whereas ERβ1 has some inhibitory actions. [ABSTRACT FROM AUTHOR]