Analysis of immunohistochemical characteristics and recurrence after complete remission with fertility preservation treatment in patients with endometrial carcinoma and endometrial atypical hyperplasia.

OBJECTIVE: To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). METHODS: The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. RESULTS: (1) The expression rate of ER in group 1 was lower than that in group 2, (P < 0.05). The expression rate of Ki-67 in group 1 was significantly higher than that in group 2, (P < 0.01). The expression rates of PR, P16, P53, and PTEN were not significantly different between the two groups (P > 0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. CONCLUSIONS: The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment.

Morphological, immunohistochemical, and genetic analyses of epithelioid gastrointestinal stromal tumors.

Epithelioid gastrointestinal stromal tumors (GISTs) are rare and may be confused with other tumors with epithelioid morphology. Therefore, herein, we collected 12 epithelioid GIST samples and summarized their morphological and immunohistochemical characteristics. Through genetic testing, we explored the correlation between morphology and gene mutations. The results showed that eight tumors showed focal or diffuse myxoid stromal changes with less cohesively arranged rhabdoid tumor cells; among these, five showed platelet-derived growth factor receptor alpha gene (PDGFRA) mutations. Signet ring cells with sclerosing stroma and receptor tyrosine kinase type III gene (KIT) mutations were present in two cases, which might be a KIT mutation-associated growth pattern in epithelioid GISTs. Succinate dehydrogenase gene (SDH) mutations were detected in three cases. Simultaneously, PDGFRA mutations were detected in two cases, and the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation was detected in another case. SDH-subunit B (SDHB) expression was partially weak and strongly diffuse in two cases with concurrent PDGFRA and SDHD mutations, respectively. The coexistence of PDGFRA and SDHD mutations may have affected SDHB expression. Altogether, we concluded that PDGFRA mutations may play an important role in co-mutant GIST pathogenesis.

Clinical features of IgG4-related retroperitoneal fibrosis among 407 patients with IgG4-related disease: a retrospective study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is recently recognized as a fibro-inflammatory condition featured by tumefactive lesions in multiple organs, and the retroperitoneum is one of the common involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with retroperitoneum lesion (IgG4-RD RPF+) and retroperitoneum free IgG4-RD (IgG4-RD RPF-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 407 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2009 and May 2019. RESULTS: Among 407 patients, 58 had retroperitoneum affected. As compared with IgG4-RD RPF- patients, IgG4-RD RPF+ patients showed older age at disease onset and diagnosis. IgG4-RD RPF+ group involved more male patients. In terms of organ involvement, IgG4-RD RPF+ group was more frequently presented with kidney involvement, while salivary gland, lacrimal gland and pancreas were more prominent in the IgG4-RD RPF- group. In addition, the CRP, ESR level and creatinine level were significantly higher in IgG4-RD RPF+ patients, and hypocomplementemia were more common in this group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD RPF+ and RPF- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.

Interleukin 17E associates with haematologic involvement and autoantibody production in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most prevalent systemic autoimmune diseases characterised by inflammation and tissue damage of exocrine glands, especially salivary or lacrimal gland. IL-17 related immune response is pathogenic with proinflammatory feature in pSS. However, whether IL-17E, an IL-17 family member, is involved in pSS pathogenesis or not, has not been determined. METHODS: Serum levels of IL-17E and IL-17A as comparison in 107 patients with pSS and 42 healthy controls were determined with multiplex cytokine assays. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was calculated. Laboratory parameters were measured by standard laboratory techniques. The inflammatory infiltration of minor labial gland biopsies was graded based on numbers of lymphocyte and quantified by Focus Score (FS). Expression of IL-17E and IL-17A in the biopsy was evaluated with immunohistochemistry. RESULTS: Significantly elevated IL-17E in pSS patients associated with ESSDAI, haematologic disorders and autoantibody production, including anti-nuclear antibodies (ANA), rheumatoid factor (RF) and anti-SSA antibodies were found. Histopathological features showed that expression of IL-17E was found in labial salivary gland and correlated with lymphocytic infiltration. CONCLUSIONS: IL-17E expression in pSS patients was increased and associated with haematologic disorders, autoantibody production and lymphocytic infiltration in salivary gland. This finding indicated that IL-17E is involved in pSS pathogenesis.

Significance of serum and pathological biomarkers in fertility-sparing treatment for endometrial cancer or atypical hyperplasia: a retrospective cohort study.

BACKGROUND: This study analyzed the changes of serum and pathological biomarkers during fertility-sparing therapy of endometrial cancer (EC) or endometrial atypical hyperplasia (EAH), to investigate their implications for early prediction of treatment efficacy. METHODS: A retrospective analysis of EC or EAH patients who received fertility-sparing therapy between 2012 and 2016 was performed. Serum and endometrium sampling were obtained for each patient at three time points: at baseline, at 3-6 months' treatment and at the end of conservative treatment. Serum biomarkers including insulin resistance (HbA1c, HOMA-IR), sex hormones and thyroid hormones were measured. Meanwhile expression of endometrial pathological biomarkers including ER, PR, PRB and Ki-67 was also assessed by immunohistochemistry. RESULTS: For the 53 recruited patients, overall complete response, recurrence and pregnancy rates were 94%, 26% and 36.4%. During the treatment, the serum biomarkers of HOMA-IR remained stable, while pathological markers including PR, PRB and Ki67 diminished significantly. Patients who achieved remission faster had significant lower HOMA-IR level and higher PRB expression at baseline. We also found a more remarkable down-regulation of PRB related with faster remission. Further multivariate analysis confirmed that baseline HOMA-IR ≥ 2.5 negatively affected treatment time to remission (OR 0.206; p = 0.017). While marked reduction of PRB (≥ 30%) at 3-6 months' treatment correlated with faster remission (OR 5.788; p = 0.010). CONCLUSION: For EC and EAH patients who received fertility-sparing therapy, baseline status of insulin resistance predicted poor response to progestin, while marked reduction of PRB following the initial 3-6 months' treatment predicted fast remission.

Use of high-resolution full-field optical coherence tomography and dynamic cell imaging for rapid intraoperative diagnosis during breast cancer surgery.

BACKGROUND: Although traditional intraoperative assessments (ie, frozen sections) may lower reoperation rates in patients with breast cancer, time/tissue limitations and accuracy concerns have discouraged their routine clinical use. Full-field optical coherence tomography (FFOCT) and dynamic cell imaging (DCI) are novel optical imaging techniques offering rapid histologic approximations that are unfettered by requisite handling steps. This study was conducted to determine the feasibility and diagnostic utility of FFOCT and DCI in examining breast and lymph node specimens during breast cancer surgery. METHODS: FFOCT and DCI were applied to normal and cancerous breast tissue, benign breast lesions, and resected axillary lymph nodes. The tissues were then subjected to conventional processing and staining (hematoxylin-eosin) for purposes of comparison. RESULTS: A total of 314 specimens, including 173 breast biopsies (malignant, 132; benign/normal, 41) and 141 resected lymph nodes (tumor-positive, 48; tumor-negative, 93), were obtained from 158 patients during breast surgery for prospective imaging evaluations. In breast cancer diagnosis, the minimum sensitivities (FFOCT, 85.6%; DCI, 88.6%) and specificities of optical imaging (FFOCT, 85.4%; DCI, 95.1%) were high, although they diverged somewhat in nodal assessments (FFOCT sensitivity, 66.7%; FFOCT specificity, 79.6%; DCI sensitivity, 83.3%; DCI specificity, 98.9%). CONCLUSIONS: These timely and tissue-sparing optical imaging techniques proved highly accurate in diagnosing breast cancer and nodal metastasis. They compare favorably with routine histologic sections and demonstrate their promise in this setting.

Efficacy and Safety of Complete Mesocolic Excision in Patients With Colon Cancer: Three-year Results From a Prospective, Nonrandomized, Double-blind, Controlled Trial.

OBJECTIVE: The aim of the study was to evaluate the oncological outcomes of complete mesocolic excision (CME) in colon cancer patients. SUMMARY BACKGROUND DATA: CME is considered a standard procedure for colon cancer patients. However, previous evidence regarding the effect of CME on prognosis has fundamental limitations that prevent it from being fully accepted. METHODS: Patients who underwent radical resection for colon cancer were enrolled between November 2012 and March 2016. According to the principles of CME, patients were stratified into 2 groups based on intraoperative surgical fields and specimen photographs. The primary outcome was local recurrence-free survival (LRFS). The clinicopathological data and follow-up information were collected and recorded. The final follow-up date was April 2016. The trial was registered in ClinicalTrials.gov (identifier: NCT01724775). RESULTS: There were 220 patients in the CME group and 110 patients in the noncomplete mesocolic excision (NCME) group. Baseline characteristics were well balanced. Compared with NCME, CME was associated with a greater number of total lymph nodes (24 vs 20, P = 0.002). Postoperative complications did not differ between the 2 groups. CME had a positive effect on LRFS compared with NCME (100.0% vs 90.2%, log-rank P < 0.001). Mesocolic dissection (100.0% vs 87.9%, log-rank P < 0.001) and nontumor deposits (97.2% vs 91.6%, log-rank P < 0.022) were also associated with improved LRFS. CONCLUSIONS: Our findings demonstrate that, compared with NCME, CME improves 3-year LRFS without increasing surgical risks.

Genomic characterisation of pulmonary subsolid nodules: mutational landscape and radiological features.

BACKGROUND: Lung adenocarcinomas (LUADs) that display radiologically as subsolid nodules (SSNs) exhibit more indolent biological behaviour than solid LUADs. SSNs, commonly encompassing pre-invasive and invasive yet early-stage adenocarcinomas, can be categorised as pure ground-glass nodules and part-solid nodules. The genomic characteristics of SSNs remain poorly understood. METHODS: We subjected 154 SSN samples from 120 treatment-naïve Chinese patients to whole-exome sequencing. Clinical parameters and radiological features of these SSNs were collected. The genomic landscape of SSNs and differences from that of advanced-stage LUADs were defined. In addition, we investigated the intratumour heterogeneity and clonal relationship of multifocal SSNs and conducted radiogenomic analysis to link imaging and molecular characteristics of SSNs. Fisher's exact and Wilcoxon rank sum tests were used in the statistical analysis. RESULTS: The median somatic mutation rate across the SSN cohort was 1.12 mutations per Mb. Mutations in EGFR were the most prominent and significant variation, followed by those in RBM10, TP53, STK11 and KRAS. The differences between SSNs and advanced-stage LUADs at a genomic level were unravelled. Branched evolution and remarkable genomic heterogeneity were demonstrated in SSNs. Although multicentric origin was predominant, we also detected early metastatic events among multifocal SSNs. Using radiogenomic analysis, we found that higher ratios of solid components in SSNs were accompanied by significantly higher mutation frequencies in EGFR, TP53, RBM10 and ARID1B, suggesting that these genes play roles in the progression of LUADs. CONCLUSIONS: Our study provides the first comprehensive description of the mutational landscape and radiogenomic mapping of SSNs.

Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients.

OBJECTIVES: IgG4-related disease (IgG4-RD) has recently been recognized as a fibro-inflammatory condition featuring tumefactive lesions in multiple organs, and the salivary gland is one of the most commonly involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with salivary gland lesions (IgG4-RD SG+) and salivary-gland-free IgG4-RD (IgG4-RD SG-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 428 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2006 and May 2018. RESULTS: Among 428 patients, 249 had salivary glands that were affected. IgG4-RD SG+ patients showed younger age at disease onset and diagnosis, and a longer interval between symptom onset and diagnosis. The IgG4-RD SG+ group involved more female patients, and allergic diseases were more common in this group. In terms of organ involvement, the IgG4-RD SG+ group were more frequently presented with lacrimal gland involvement, while lymph node, retroperitoneal fibrosis, pancreas, biliary system, kidney and aorta were more prominent in the IgG4-RD SG- group. In addition, the serum IgG4 level, IgG4/IgG ratio and IgE level were significantly higher in IgG4-RD SG+ patients. Patients with eosinophilia were more common in the IgG4-RD SG+ group, while elevated ESR, CRP and positive ANA were more common in the IgG4-RD SG- group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD SG+ and SG- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.

Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort.

OBJECTIVES: Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition. METHODS: We performed a retrospective study of 277 IgG4-RD patients at Peking University People's Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition. RESULTS: The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different. CONCLUSION: The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.

Enhanced Rim on MDCT of Colorectal Liver Metastases: Assessment of Ability to Predict Progression-Free Survival and Response to Bevacizumab-Based Chemotherapy.

OBJECTIVE. The purpose of this article is to evaluate the enhanced rim on the portal venous phase (PVP) on MDCT as a predictor of 1-year progression-free survival (PFS) and response to bevacizumab-based chemotherapy in patients with colorectal liver metastases (CRLM). MATERIALS AND METHODS. We retrospectively identified 111 patients with primary unresectable CRLM treated with bevacizumab-based chemotherapy at two institutions between 2012 and 2018. Pretreatment contrast-enhanced MDCT images were reviewed and data on clinical characteristics were collected from the electronic medical records. Univariable and multivariable analyses were conducted to assess several imaging features and clinical characteristics as potential predictors of 1-year PFS and objective response rate (ORR). RESULTS. After 1 year of follow-up, liver metastatic tumor progression was detected in 52 patients (46.8%) after bevacizumab-based chemotherapy. A log-rank test showed that enhanced rim on PVP (chi-square test, 5.862; p = 0.015) and the occurrence of liver resection surgery (chi-square test, 7.836; p = 0.005) were significant predictors of 1-year PFS. Multivariable analysis showed that enhanced rim on PVP images was an independent predictor of 1-year PFS (hazard ratio, 0.510; 95% CI, 0.282-0.926; p = 0.027) and ORR (odds ratio, 4.694; p < 0.001). CONCLUSION. The presence of an enhanced rim on PVP MDCT is an independent predictor of survival and response to bevacizumab-based chemotherapy among patients with CRLM.

Identification of ampullary carcinoma mixed subtype using a panel of six antibodies and its clinical significance.

OBJECTIVES: To investigate the function of immunomarkers CK7, CK20, CK17, CDX2, MUC1, and MUC2 in the identification of primary ampullary carcinoma mixed subtype. METHODS: Forty-two cases of primary ampullary carcinoma were performed by immunohistochemical studies. The correlation between the mixed subtype and the other two subtypes and patient survival data was analyzed using the SPSS 16.0 statistical software. RESULTS: Among 42 cases, 12 (28.6%) cases were classified as mixed subtype, which showed variable expression patterns: 91.7% (11/12) for CK7, 83.3% (10/12) for CK20; 66.7% (8/12) for CK17, CDX2, and MUC1; and 50% (6/12) for MUC2. Ten (83.3%) mixed types coexpressed four or more immunomarkers. Eight (19%) intestinal subtypes mainly showed a positive expression of CK20, CDX2, and MUC2. Twenty-two (52.4%) pancreaticobiliary subtypes showed a positive expression of CK7, MUC1, and CK17. Stages III and IV diseases in mixed subtype (25%) and intestinal subtype (25%) were less than pancreaticobiliary subtype(63.6%) (p = 0.039). Follow-up data appeared to show a better survival rate for patients with mixed subtype than those with pancreaticobiliary subtypes. CONCLUSION: Immunohistochemical staining provided a more reliable means of diagnosing mixed ampulla carcinoma. Accurate subtyping of ampullary carcinoma is clinically important to select effective chemotherapy regimens and to assess disease prognosis.

MRI for Restaging Locally Advanced Rectal Cancer: Detailed Analysis of Discrepancies With the Pathologic Reference Standard.

OBJECTIVE. The purpose of this study was to analyze causes of discrepancies between restaging MRI and pathologic findings in the assessment of morphologic indicators of tumor response in patients with rectal cancer who have undergone neoadjuvant treatment. MATERIALS AND METHODS. MRI and pathologic data from 57 consecutively registered patients who underwent neoadjuvant treatment and total mesorectal excision between August 2015 and July 2018 were retrospectively analyzed. The sensitivity and specificity of restaging MRI in determining tumor regression grade, T category, N category, circumferential resection margin, and extramural vascular invasion were calculated with pathologic results as the reference standard. One-by-one comparisons between MRI and pathologic findings were conducted to identify causes of discrepancies. RESULTS. The sensitivity of MRI in determining tumor regression grades 3-5 was 77.1%; T3 and T4 category, 100.0%; node-positive disease, 75.0%; circumferential resection margin, 87.5%; and extramural vascular invasion, 91.7%. The specificity values were 72.7%, 62.5%, 70.7%, 85.7%, and 64.4%. Overstaging was mainly caused by misinterpretation of fibrotic areas as residual tumor. Inflammatory cell infiltration could appear as high signal intensity in fibrotic areas on DW images, an appearance similar to that of residual tumor. Edematous mucosa and submucosa adjacent to the tumor and muscularis propria could also be mistaken for residual tumor because of their intermediate signal intensity on T2-weighted MR images. CONCLUSION. MRI was prone to overstaging of disease. Discrepancies between MRI and pathologic findings were mainly caused by misinterpretation of fibrosis. Inflammatory cell infiltration, pure mucin, edematous mucosa and submucosa adjacent to the tumor, and muscularis propria could also be misinterpreted as residual tumor.

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. METHODS: A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. RESULTS: A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). CONCLUSIONS: Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival.

OBJECTIVE: Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown. METHODS: To investigate the clinical significance of BMPR2 and HIF1-α in osteosarcoma, we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry. Meanwhile, we conducted a follow-up to examine the metastatic behavior and overall survival (OS) of osteosarcoma patients. RESULTS: Among 103 tissues, 61 cases had BMPR2-positive expression and 57 cases had HIF1-α positive expression. A significant correlation was noticed between BMPR2 and HIF1-α expression in osteosarcoma specimens (P=0.035). Receiver-operating characteristic (ROC) curves were calculated to investigate the predictive value of the two markers in tumor metastasis. By means of univariate and multivariate analysis, BMPR2 and HIF1-α expression, as well as higher tumor grade, were identified as significant risk factors for OS in patients with osteosarcoma. Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-α positive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining. CONCLUSIONS: It can be concluded that BMPR2 and HIF1-α expression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

Ca2+ channel subunit α 1D promotes proliferation and migration of endometrial cancer cells mediated by 17ß-estradiol via the G protein-coupled estrogen receptor.

Calcium and calcium channels are closely related to the estrogen-induced nongenomic effect of endometrial carcinoma, but the specific role of calcium channels is unknown. This study aimed to explore the expression and the biologic effect of the L-type calcium channel in endometrial carcinoma cells and to clarify the molecular mechanism of the relationship between L-type calcium channels and estrogen. The immunohistochemical results showed that Ca(2+) channel subunit α 1D (Cav1.3) expression was high in atypical hyperplasia (1.90 ± 0.35) and endometrial carcinoma tissues (2.05 ± 0.82) but weak (0.80 ± 0.15) in benign endometrial tissues (P < 0.05). Treatment with 17ß-estradiol rapidly increased Cav1.3 expression in a dose- and time-dependent manner, and 100 nM cell-impermeable ß-estradiol-6-(O-carboxymethyl)oxime:bovine serum albumin also promoted Cav1.3 expression. Transfection with small interfering RNA against G protein-coupled estrogen receptor (GPER) suppressed estrogen-induced up-regulation of Cav1.3 compared with control cells and markedly reduced the estrogen-induced phosphorylation of ERK1/2 and CREB. Knocking down the Cav1.3 significantly suppressed estrogen-stimulated Ca(2+) influx, cell proliferation, and migration in endometrial cancer cells. Taken together, Cav1.3 was overexpressed in atypical hyperplasia and endometrial carcinoma, and the estrogen-induced phosphorylation of downstream molecular ERK1/2 and CREB is the result of activation of the GPER pathway. L-type channel Cav1.3 is required for estrogen-stimulated Ca(2+) influx and contributes broadly to the development of endometrial cancer. The Cav1.3 channel may be a new target for endometrial carcinoma treatment.

Prior Tubal Ligation Might Influence Metastatic Spread of Nonendometrioid Endometrial Carcinoma.

OBJECTIVE: The exfoliation of endometrial carcinoma might intraperitoneally spread through the fallopian tube. We analyzed the influence of prior tubal ligation (TL) in endometrial carcinoma to evaluate whether it can prevent the process and improve patients' survival. METHODS: A total of 562 patients with a diagnosis of endometrial carcinoma at the Peking University People's Hospital between July 1995 and June 2012 were enrolled in this study. The patients were divided into 2 groups based on the presence or absence of prior TL. International Federation of Gynecology and Obstetrics stage distributions, recurrence rates, survival status, and histopathological findings were compared between the 2 groups. Kaplan-Meier estimates and log-rank tests were used to compare the survival status based on TL in the overall population and stratified by histopathological subtypes and International Federation of Gynecology and Obstetrics stages. Cox models analysis was used to estimate the hazard ratios and 95% confidence intervals for associations between TL and carcinoma-specific mortality. All statistical tests were 2-sided. RESULTS: Of the 562 patients, 482 (85.7%) had a diagnosis of endometrioid and 80 patients (14.2%) with nonendometrioid carcinoma. Tubal ligation was associated with negative peritoneal cytology in the total population (P = 0.015) and in patients with endometrioid carcinomas (P = 0.02) but not help to reduce carcinoma-specific mortality (P = 0.095 and P = 0.277, respectively). In the nonendometrioid group, TL was not only associated with negative peritoneal cytology (P = 0.004) but also with lower stage (P < 0.001) and lower recurrence rate(P < 0.005), resulting in improved prognosis (P = 0.022). In Cox models analysis adjusted for covariates, TL was inversely associated with lower endometrial carcinoma-specific mortality (hazard ratio, 0.47; 95% confidence interval, 0.14-2.6). CONCLUSION: Tubal ligation was associated with lower positive peritoneal cytology, stages, and recurrence rate, and improved prognosis among patients with nonendometrioid carcinoma. Tubal ligation might influence metastatic spread of nonendometrioid endometrial carcinoma. It could also help to reduce positive peritoneal cytology among patients with endometrioid carcinoma, but lacked prognostic significance.

[Pathologic features of fallopian tubal fimbriae in patients with endometrial serous carcinoma].

OBJECTIVE: To discuss the potential relationship between endometrial serous carcinoma (ESC) and tubal epithelial lesions by pathologic examination of fallopian tubes with ESC. METHODS: A total of 30 cases of typical ESC were reexamined and chosen by the pathologist. In each case, bilateral fallopian tubes were submitted to examination of pathologic morphology and immunostaining for p53, annexin IV (ANX-IV), human epidermal growth factor receptor 2 (HER2)/neu, and high-mobility group protein A2 (HMGA2). RESULTS: Fallopian tubal epithelial lesions were found in 15 cases, including 9 cases tubal serous carcinoma, 2 cases serous tubal intraepithelial carcinoma (STIC) and 2 cases epithelial hyperplasia. Both sides of tubal serous carcinoma and STIC were found in 1 case. The results showed the positive expression for p53 in 26 (87%) out of 30 endometrial malignant specimens tissues and 9 (30%) tubal tissues samples (P > 0.05). Twenty-five (83%) endometrial malignant specimens tissues and 6 (20%) tubal tissues samples showed the positive expression of ANX-IV. Twenty-one (70%) endometrial malignant tissues and 7 (23%) tubal tissues showed the positive expression of HER2/neu. Twenty-five (83%) endometrial malignant tissues and 6 (20%) tubal tissues showed the positive expression of HMGA2. While, there were significant differences among the expression of three proteins between endometrium and the fallopian tube site (all P < 0.05). CONCLUSIONS: STIC may be associated with the occurrence of ESC. The expression of p53 was positively correlated between the fallopian tube and the endometrium. ANX-IV, HER2/neu and HMGA2 were extensively expressed in ESC.

[Age correlates with Gleason score in patients with prostate adenocarcinoma].

OBJECTIVE: To investigate the correlation between age and Gleason score (GS) in patients with prostate adenocarcinoma. METHODS: This study included 674 patients with pathologically confirmed prostate adenocarcinoma. We determined the GS, primary grade, and secondary grade of the cases, and compared them among different age groups. RESULTS: The mean age of the patients was (70.22 ± 8.26) yr, ranging from 25 to 96 years, (69.06 ± 8.35) yr in those with GS 6, (70.55 ± 8.16) yr in GS 7, (70.99 ± 6.54) yr in GS 8, (71.56 ± 9.18) yr in GS 9, and (72.79 ± 11.36) in GS 10. The mean GS, primary grade, and secondary grade were 7.08 ± 1.09, 3.54 ± 0.72, and 3.53 ± 0.66, respectively, and the mean GSs in the < 60 yr, 60-69 yr, 70-79 yr, and ≥ 80 yr groups were 6.86 ± 1.10, 6.99 ± 1.10, 7.08 ± 1.04, and 7.38 ± 1.23, respectively. Those with GS 6, 7, and ≥ 8 accounted for 37.7%, 34.3%, and 28.0%, respectively. The patients aged < 60, 60-69, 70-79, and ≥ 80 years constituted 10.5% (71/674), 30.6% (206/674), 47.6% (321/674), and 11.3% (76/674), respectively. The age of the patients was significantly correlated with GS (r2 = 0.013, P = 0.003) and the primary grade (r2 = 0.014, P = 0.002), but not the secondary grade (r2 = 0.005, P = 0.055). CONCLUSION: Of the prostate adenocarcinoma patients, those aged ≥ 70 years form a larger proportion, and those with GS ≥ 7 comprise a higher percentage. The age of the patient is correlated with Gleason score but has a limited value in its prediction.

[Influence of sampling satisfaction using endometrial sampling device and related factors for pathology diagnostic accordance rate].

OBJECTIVE: To observe the satisfaction of obtaining endometrial tissue in using endometrial sampling device and explore the influence for pathology diagnostic accordance rate, and to discuss the problem needs to focus in obtaining endometrial tissue with endometrial sampling device for endometrial cancer and precancerous lesion screening. METHODS: Totally 204 cases using endometrial sampling device with the subsequent diagnostic curettage, hysteroscopy, or hysterectomy were collected. A comparison of pathological diagnosis between two methods was made. The relationship among specimen quantity, proficiency, pathological types and diagnostic accordance rate were analyzed. RESULTS: The diagnostic accordance rate of endometrial cancer and precancerous lesion of two methods was 67% (20/30). 92.2% (188/204) cases successfully got the endometrial glands, 77.0% (157/204) cases got ≥ 5 specimens of glands and 62.3% (127/204) cases got ≥ 10 specimens of glands. When obtaining ≥ 5 but < 10 endometrial glands, the diagnostic accordance rate was 76.7% (23/30); however, obtaining ≥ 10 endometrial glands, the diagnostic accordance rate was 92.9% (118/127). The degree of specimen satisfaction of the first phase was lower than the second phase. CONCLUSIONS: Obtaining ≥ 5 endometrial glands in using endometrial sampling device could satisfy the requirement of the basic pathological diagnosis. The proficiency of sampling and the pathological types could influence the degree of specimen satisfaction, and then influence the diagnostic accordance rate.