Comprehensive analysis reveals potential therapeutic targets and an integrated risk stratification model for solitary fibrous tumors.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs.

A potential immunotherapy target for breast cancer: parenchymal and immune-stromal expression of the NLRP3 inflammasome pathway.

BACKGROUND: The NOD-, LRR- and pyrin domain­containing 3 (NLRP3) inflammasome is a critical component of the innate immune system. It has been known to play an important role in the carcinogenesis and prognosis of breast cancer patients. While the clinical evidence of the relationship between NLRP3 inflammasome activation and long-term survival is still limited, the possible roles of parenchymal or immune-stromal cells of breast cancer tissues in contributing to such carcinogenesis and progression still need to be clarified. This study is an analysis of patients receiving breast cancer surgery in a previous clinical trial. METHODS: Immunohistochemistry (IHC) was used to detect the expression levels of NLRP3 inflammasome pathway-related proteins, including NLRP3, caspase-1, apoptosis-associated speck-like protein (ASC), IL-1ß, and IL-18, in parenchymal and immune-stromal cells of breast cancer tissues compared to those of adjacent normal tissues, respectively. The relationship between NLRP3 inflammasome expression and clinicopathological characteristics, as well as 5-year survivals were analyzed using the Chi-square test, Kaplan-Meier survival curves, and Cox regression analysis. RESULTS: In the parenchymal cells, ASC and IL-18 protein levels were significantly up-regulated in breast cancer tissues compared with adjacent normal tissues (P<0.05). In the immune-stromal cells, all the five NLRP3 inflammasome pathway-related proteins were significantly elevated in breast cancer tissues compared with adjacent normal tissues (P < 0.05). Carcinoma cell embolus was found to significantly correlate with high NLRP3 expression in parenchymal cells of the tumor (x2=4.592, P=0.032), while the expression of caspase-1 was negatively correlated with tumor progression. Histological grades were found to have a positive correlation with IL-18 expression in immune-stromal cells of the tumor (x2=14.808, P=0.001). Kaplan-Meier survival analysis revealed that high IL-18 expression in the immune-stromal cells and the positive carcinoma cell embolus were both associated with poor survival (P < 0.05). The multivariable Cox proportional hazards regression model implied that the high IL-18 expression and positive carcinoma cell embolus were both independent risk factors for unfavorable prognosis. CONCLUSIONS: The activation of NLRP3 inflammasome pathways in immune-stromal and tumor parenchymal cells in the innate immune system was not isotropic and the main functions are somewhat different in breast cancer patients. Caspase-1 in parenchymal cells of the tumor was negatively correlated with tumor progression, and upregulation of IL-18 in immune-stromal cells of breast cancer tissues is a promising prognostic biomarker and a potential immunotherapy target. TRIAL REGISTRATION: This clinical trial has been registered at the Chictr.org.cn registry system on 21/08/2018 (ChiCTR1800017910).

Gastric cancer with repeated metastasis in the colonic lumen: a case report and multi-surgical experience.

Poorly differentiated gastric adenocarcinoma is commonly associated with lymph node metastasis, peritoneal spread, and liver metastasis but rarely with intraintestinal metastasis. Most patients with metastatic gastric carcinoma are unable to undergo surgical treatment and have a poor prognosis. A 42-year-old man with hunger-related abdominal pain was diagnosed as having gastric cancer. After the first surgery (distal partial gastrectomy) and the second surgery (gastric stump carcinoma (GSC) resection), the patient suffered repeated multiple intracolonic metastases and underwent three additional resection operations. The patient survived for 154 months after the first operation. In patients with gastric carcinoma that metastasizes to the colonic lumen, radical resection, if possible, can extend survival. Once patients develop extensive extraintestinal metastasis, radical resection cannot be performed, and patients often exhibit a poor prognosis.

Quantified MRI and 25OH-VitD3 can be used as effective biomarkers for patients with neoadjuvant chemotherapy-induced liver injury in CRCLM?

BACKGROUND: To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS). METHODS: 63 patients with pathologically confirmed colorectal adenocarcinoma received 4-6 courses of NC before liver resection and underwent magnetic resonance imaging (MRI) with iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification and IVIM sequences. Blood samples were analyzed using CTCAE. Pathological changes of liver tissues outside the metastases were assessed as the gold standard, and receiver operating characteristic (ROC) curves were analyzed. RESULTS: 16 cases had CASH liver injury, 14 cases had SOS changes, and 4 cases had CASH and SOS, and 7 showed no significant changes. Consistency between biochemical indices and pathological findings was poor (kappa = 0.246, p = 0.005). The areas under the ROC curve (AUCs) of ALT, AST, ALP, GGT, and TBIL were 0.571-0.691. AUCs of D, FF, and 25OH-VitD3 exceeded 0.8; when considering these markers together, sensitivity was 85.29% and specificity was 93.13%. ANOVA showed statistically significant differences among D, FF, and 25OH-VitD3 for different grades of liver injury (F = 4.64-26.5, p = 0.000-0.016). CONCLUSIONS: D, FF, and 25OH-VitD3 are biomarkers for accurate prediction of NC-induced liver injury in patients with CRCLM, while FF and 25OH-VitD3 might be beneficial to distinguish liver injury grades. TRIAL REGISTRATION: Current Trials was retrospectively registered as ChiCTR1800015242 at Chinese Clinical Trial Registry on March 16, 2018.

MicroRNA-429 inhibits bone metastasis in breast cancer by regulating CrkL and MMP-9.

Bone metastasis is common in late-stage breast cancer patients and leads to skeletal-related events that affect the quality of life and decrease survival. Numerous miRNAs have been confirmed to be involved in metastatic breast cancer, such as the miR200 family. Our previous study identified microRNA-429 (miR-429) as a regulatory molecule in breast cancer bone metastasis. However, the effects of miR-429 and its regulatory axis in the metastatic breast cancer bone microenvironment have not been thoroughly investigated. We observed a positive correlation between miR-429 expression in clinical tissues and the bone metastasis-free interval and a negative correlation between miR-429 expression and the degree of bone metastasis. We cultured bone metastatic MDA-MB-231 cells and used conditioned medium (CM) to detect the effect of miR-429 on osteoblast and osteoclast cells in vitro. We constructed an orthotopic bone destruction model and a left ventricle implantation model to examine the effect of miR-429 on the metastatic bone environment in vivo. The transfection experiments showed that the expression levels of V-crk sarcoma virus CT10 oncogene homolog-like (CrkL) and MMP-9 were negatively regulated by miR-429. The in vitro coculture experiments showed that miR-429 promoted osteoblast differentiation and that CrkL promoted osteoclast differentiation. The two animal models showed that miR-429 diminished local bone destruction and distant bone metastasis but CrkL enhanced these effects. Furthermore, CrkL and MMP-9 expression decreased simultaneously in response to increased miR-429 expression. These findings further reveal the possible mechanism and effect of the miR-429/CrkL/MMP-9 regulatory axis in the bone microenvironment in breast cancer bone metastasis.

Quantitative features of dual-energy spectral computed tomography for solid lung adenocarcinoma with EGFR and KRAS mutations, and ALK rearrangement: a preliminary study.

BACKGROUND: The present work aimed to evaluate radio-genomic associations of quantitative parameters obtained by dual-energy spectral computed tomography (DESCT) for solid lung adenocarcinoma with epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, as well as anaplastic lymphoma kinase (ALK) rearrangement. METHODS: Ninety-six cases of solid lung cancer were selected and assessed for EGFR and KRAS mutations, and ALK rearrangement. Then, they underwent chest DESCT, and quantitative parameters, including water concentration (WC), iodine concentration (IC), CT value at 70 keV, effective atomic number (Effective-Z) and spectral Hounsfield unit curve slope (λHU slope) were measured. Finally, the associations of quantitative radiological features with various gene alterations were evaluated. RESULTS: The positive rates were 51.0% (49/96) for EGFR, 13.5% (13/96) for KRAS and 16.7% (16/96) for ALK. In univariate analysis, EGFR mutation was associated with smoking status, CT value at 70 keV, IC, Effective-Z, and λHU slope; KRAS mutation was associated with CT value at 70 keV, IC, Effective-Z, and λHU slope, and ALK rearrangement was correlated with age and WC. In multivariate analysis, smoking status (OR =2.924, P=0.019) and CT value at 70 keV (OR =1.036, P=0.006) were significantly associated with EGFR mutation; Effective-Z and age were significantly associated with KRAS mutation (OR =0.047, P=0.032) and ALK rearrangement (OR =0.933, P=0.008), respectively. CONCLUSIONS: Quantitative analysis of DESCT could help detect solid lung adenocarcinoma harboring EGFR or KRAS mutation, or ALK rearrangement.

Prediction for early recurrence of intrahepatic mass-forming cholangiocarcinoma: quantitative magnetic resonance imaging combined with prognostic immunohistochemical markers.

BACKGROUND: Partial hepatectomy is the first option for intrahepatic mass-forming cholangiocarcinoma (IMCC) treatment, which would prolong survival. The main reason for the poor outcome after curative resection is the high incidence of early recurrence (ER). The aim of this study was to investigate the combined predictive performance of qualitative and quantitative magnetic resonance imaging (MRI) features and prognostic immunohistochemical markers for the ER of IMCC. METHODS: Forty-seven patients with pathologically proven IMCC were enrolled in this retrospective study. Preoperative contrast-enhanced MRI and post-operative immunohistochemical staining of epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptor (VEGFR), P53 and Ki67 were performed. Univariate analysis identified clinic-radiologic and pathological risk factors of ER. Radiomics analysis was performed based on four MRI sequences including fat suppression T2-weighted imaging (T2WI/FS), arterial phase (AP), portal venous phase (PVP), and delayed phase (DP) contrast enhanced imaging. A clinicoradiologic-pathological (CRP) model, radiomics model, and combined model were developed. And ROC curves were used to explore their predictive performance for ER stratification. RESULTS: Enhancement patterns and VEGFR showed significant differences between the ER group and non-ER group (P = 0.001 and 0.034, respectively). The radiomics model based on AP, PVP and DP images presented superior AUC (0.889, 95% confidence interval (CI): 0.783-0.996) among seven radiomics models with a sensitivity of 0.938 and specificity of 0.839. The combined model, containing enhancement patterns, VEGFR and radiomics features, showed a preferable ER predictive performance compared to the radiomics model or CRP model alone, with AUC, sensitivity and specificity of 0.949, 0.875 and 0.774, respectively. CONCLUSIONS: The combined model was the superior predictive model of ER. Combining qualitative and quantitative MRI features and VEGFR enables ER prediction, thus facilitating personalized treatment for patients with IMCC.

Erratum: Spread through air spaces predicts a worse survival in patients with stage I adenocarcinomas >2 cm after radical lobectomy.

[This corrects the article DOI: 10.21037/jtd.2018.09.22.].

Quantitative magnetic resonance imaging evaluation of hepatic fat content with iron deposition: will it be disturbed?

OBJECTIVE: To explore noninvasive assessment of liver fat content with iron deposition using magnetic resonance (MR) quantitative technology. METHODS: A water-fat phantom with iron deposition containing 63 vials with predetermined fat percentages and iron concentrations was constructed. Thirty-three patients underwent fat quantitative MR examinations. The fat fraction (FF) was determined by three Dixon techniques. Pathological evaluation findings and the steatosis area rate (SAR) were used as the gold standards. RESULTS: FFIOP and FFLAVA-Flex significantly differed from FFTEST for iron concentrations of 1 to 30 µg/mL and fat components of 10% to 80%. Using the three Dixon techniques, FFIOP was 15.76% ± 6.98%, FFLAVA-Flex was 16.71% ± 6.77%, and FFIDEAL IQ was 13.18% ± 6.42% in patients without liver cirrhosis; these values in patients with liver cirrhosis were 20.35% ± 6.11%, 20.89% ± 8.49%, and 12.86% ± 4.00%, respectively. The SAR in patients without and with liver cirrhosis was 11.31% ± 5.89% and 9.84% ± 4.17%, respectively. There were significant positive correlations between FFIDEAL IQ and SAR with or without liver cirrhosis. CONCLUSION: Iron deposition must be considered when using quantitative MR techniques to evaluate the hepatic fat content. Compared with the IOP and LAVA-Flex techniques, the IDEAL IQ technique has more stability and accuracy in measurement of the hepatic fat content, free from iron deposition.

Generalized linear model (GLM) analysis: Multivariables of microcalcification specimens obtained via X-ray guided by stereotactic wire localization biopsy.

OBJECTIVE: To retrospectively explore correlation of the resected specimen volume of breast microcalcification lesions and endogenous and exogenous factors of stereotactic needle localization biopsy (SNLB). MATERIALS AND METHODS: Totally 214 patients underwent SNLB for non-palpable breast lesion with microcalcification lesions. Of 211 patients, 198 patients underwent single needle localization and 13 patients underwent multi-needle localization (26 lesions). Lesion sizes, distribution characteristics, lesion localization accuracy and resected specimen volumes were recorded and analyzed using a generalized linear model (GLM). RESULTS: The average lesion diameter is 2.63±1.73 cm. The localization accuracy of 187 lesions were moderate, 26 were too deep and 11 were too superficial. The mean resected specimen volume (V) was 17.51±5.14 cm3. One-way ANOVA analysis showed that 3 factors, including lesion sizes, distribution characteristics and the localization accuracy were associated with resected specimen volume (F = 67.56-112.78, P < 0.001). GLM revealed that lesion sizes, single clustered distribution and accurate localization were significant factors for resected specimen volume (F = -4.82-11.36, P < 0.05). The ratio (%) of the resected specimen volume to the involved breast volume (V0) was defined as the degree of breast defect. The mean breast defect of 125 benign patients (V/V0) was 27.5% ranging from 10.1% to 42.3%. CONCLUSION: Average lesion diameter and localization accuracy are highly significant variables for the resected specimen volume. Localization accuracy as a subjective controllable variable is one of the important factors that determine the volume of lesion resection. Single clustered distribution was more susceptible localization accuracy than other characteristic distributions. Improving localization accuracy can reduce resected specimen volume, which can reduce breast defect to a certain extent.

Spread through air spaces predicts a worse survival in patients with stage I adenocarcinomas >2 cm after radical lobectomy.

BACKGROUND: The aim of this study was to evaluate the significance of spread through air spaces (STAS) in early lung adenocarcinomas after radical lobectomy and lymphadenectomy. METHODS: A total of 242 patients with lung adenocarcinomas less than 4 cm (8th pStage I) were selected from the lung cancer patients surgically treated from January, 2009 to September, 2011. Pathological review focused on STAS as well as histological subtypes, blood vessel & neural invasion, pathological tumor size etc. Recurrence or disease-free survival (DFS) and overall survival (OS) were compared between patients as stratified by STAS and tumor size. RESULTS: STAS was observed in 33.47% (81/242) patients, which was significantly correlated with histological predominant subtype (χ2=25.903, P=0.093×10-3) and differentiation grade (χ2=23.986, P=0.025×10-3). Patients with STAS (+) showed a comparable PFS (P=0.268) and OS rates (P=0.100) in all stage I cases, but a significant lower PFS (P=0.029) and OS (P=0.013) in tumors within 2< tumors ≤4 cm. Multivariate analysis revealed STAS to be an independent worse prognostic factor in lung adenocarcinomas within 2< tumors ≤4 cm, both for PFS (P=0.004) and OS (P=0.002), while no significant difference was found in patients with tumors ≤2 cm (PFS, P=0.537; OS, P=0.448), after adjusting by other clinicopathological parameters as age, gender, smoking etc. CONCLUSIONS: Presence of STAS was a significant worse predictor for pStage I patients with lung adenocarcinoma >2 cm who underwent radical lobectomy, while it is not significant in patients with tumor ≤2 cm. These findings may be helpful in assessing postoperative therapy stratified by tumor size and STAS status.

Genetic Features of Aflatoxin-Associated Hepatocellular Carcinoma.

BACKGROUND & AIMS: Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC). However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure. We investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen. METHODS: We obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China-a high-risk region for aflatoxin exposure (38.2% of food samples test positive for aflatoxin contamination). Somatic variants were identified using GATK Best Practices Pipeline. We validated part of the mutations from whole-genome sequencing and whole-exome sequencing by Sanger sequencing. We also analyzed genomes of 1072 HCCs, obtained from 5 datasets from China, the United States, France, and Japan. Mutations in 49 aflatoxin-associated HCCs and 1072 HCCs from other regions were analyzed using the Wellcome Trust Sanger Institute mutational signatures framework with non-negative matrix factorization. The mutation landscape and mutational signatures from the aflatoxin-associated HCC and HCC samples from general population were compared. We identified genetic features of aflatoxin-associated HCC, and used these to identify aflatoxin-associated HCCs in datasets from other regions. Tumor samples were analyzed by immunohistochemistry to determine microvessel density and levels of CD34 and CD274 (PD-L1). RESULTS: Aflatoxin-associated HCCs frequently contained C>A transversions, the sequence motif GCN, and strand bias. In addition to previously reported mutations in TP53, we found frequent mutations in the adhesion G protein-coupled receptor B1 gene (ADGRB1), which were associated with increased capillary density of tumor tissue. Aflatoxin-associated HCC tissues contained high-level potential mutation-associated neoantigens, and many infiltrating lymphocytes and tumors cells that expressed PD-L1, compared to HCCs not associated with aflatoxin. Of the HCCs from China, 9.8% contained the aflatoxin-associated genetic features, whereas 0.4%-3.5% of HCCs from other regions contained these genetic features. CONCLUSIONS: We identified specific genetic and mutation features of HCCs associated with aflatoxin exposure, including mutations in ADGRB1, compared to HCCs from general populations. We associated these mutations with increased vascularization and expression of PD-L1 in HCC tissues. These findings might be used to identify patients with HCC due to aflatoxin exposure, and select therapies.

A new prognostic histopathologic classification of nasopharyngeal carcinoma.

BACKGROUND: The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response. METHODS: We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS). RESULTS: The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P < 0.001). In multivariate models, patients with MSEC had a shorter OS than patients with EC (HR = 1.44, 95% CI = 1.27-1.62), SC (HR = 2.00, 95% CI = 1.76-2.28), or SCC (HR = 4.23, 95% CI = 3.34-5.38). Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC (HR = 0.67, 95% CI = 0.56-0.80), MSEC (HR = 0.58, 95% CI = 0.49-0.75), and possibly for those with SCC (HR = 0.63; 95% CI = 0.40-0.98), but not for patients with SC (HR = 0.97, 95% CI = 0.74-1.28). CONCLUSIONS: The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associated with a poor prognosis.

Overexpression of the DEC1 protein induces senescence in vitro and is related to better survival in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death in China and has limited effective therapeutic options except for early surgery, since the underlying molecular mechanism driving its precursor lesions towards invasive ESCC is not fully understood. Cellular senescence is the state of the permanent growth arrest of a cell, and is considered as the initial barrier of tumor development. Human differentiated embryo chondrocyte expressed gene 1 (Dec1) is an important transcription factor that related to senescence. In this study, DEC1 immunohistochemical analysis was performed on tissue microarray blocks constructed from ESCC combined with adjacent precursor tissues of 241 patients. Compared with normal epithelia, DEC1 expression was significantly increased in intraepithelial neoplasia and DEC1 expression was significantly decreased in ESCC in comparison with intraepithelial neoplasia. In vitro, DEC1 overexpression induced cellular senescence, and it inhibited cell growth and colony formation in ESCC cell line EC9706. Fresh esophagectomy tissue sections from five ESCC patients were detected by immunohistochemistry of DEC1 and senescence-associated ß-galactosidase (SA-ß-Gal) activity, and strongly positive expression of DEC1 was correlated to more senescent cells in these fresh tissue sections. Kaplan-Meier method analysis of the 241 patients revealed that DEC1 expression levels were significantly correlated with the survival of ESCC patients after surgery. The expression levels of DEC1 were also correlated with age, tumor embolus, depth of invasion of ESCC, lymph metastasis status and pTNMs. These results suggest that DEC1 overexpression in precursor lesions of ESCC is a protective mechanism by inducing cellular senescence in ESCC initiation, and DEC1 may be a potential prognostic marker of ESCC.

[Expression of intrahepatic CD4+ CD25+ regulatory T cells in patients with chronic hepatitis B].

OBJECTIVE: To investigate the expression and distribution of intrahepatic CD4+ CD25+ regulatory T cells in immuno-tolerant and immuno-clearance phase of patients with chronic hepatitis B. METHODS: The expression of FoxP3 was detected in 19 cases of immuno-tolerant phase and 12 cases of immuno-clearance phase by immunohistochemistry. The relation between the intrahepatic expression of FoxP3 and the clinicopathological features were analyzed. RESULTS: The positive signal of FoxP3 is located in nuclear of lymphocyte and mainly aggregated in portal areas as well as occasionally scattered in hepatic sinusoids. The expression of intrahepatic FoxP3 in the group of immuno-tolerant phase was significantly increased than those in normal control (P < 0.01), and greatly decreased than those in immuno-clearance phase (P < 0.01). No correlation was observed among the expression of intrahepatic FoxP3, ALT, levels of HBV DNA, HBeAg positive, in patients of immuno-clearance phase, respectively. There were significant differences between immuno-tolerant phase and immuno-clearance phase age, ALT, TBIL, PTA, HBV-DNA and detection of HBeAg but not in sex and family history of HBV infection. CONCLUSION: CD4+ CD25+ regulatory T cells may play important roles in the clearance of HBV as well as in liver inflammation and injury during chronic HBV infection.

[Detection of CD4+CD25+ regulatory T cells in liver tissues of fibrosing cholestatic hepatitis after liver and kidney transplantation].

OBJECTIVES: To study the expression and distribution of CD4+CD25+ regulatory T cells (Treg) in liver tissues of patients with fibrosing cholestatic hepatitis (FCH) after liver and kidney transplantation and to investigate their roles in the pathogenesis of FCH. METHODS: Liver biopsy specimens from five patients with FCH were studied histopathologically. A specific marker for CD4+CD25+ regulatory T cells in those specimens was detected with anti-FOXP3 monoclonal antibody by immunohistochemistry. Apoptoses of hepatocytes were detected with in situ apoptosis detection TUNEL kit. RESULTS: Fibrosis in portal and around portal areas, cholestasis in some of the hepatocytes and canaliculi, widespread ballooning and ground-glass appearance of liver cells, and positivity of HBsAg and HBcAg and Pre-S1 protein were seen in the livers of all cases. The positive signal of FOXP3 was located in the cytoplasm of lymphocytes and the positive cells were mainly aggregated in the portal areas as well as occasionally appearing in the hepatic sinusoids. There were many more apoptotic hepatocytes near the portal areas. CONCLUSION: Fibrosing cholestatic hepatitis has specific pathological characteristics which might be caused by high expressions of FOXP3 in liver tissues.

[Pathology of AIDS-related lymphadenopathy and its relationship to expression of CD4 + CD25 + regulatory T cells in lymphoid node tissue].

OBJECTIVE: To observe the pathology of AIDS-related lymphadenopathy and its relationship to the expression and distribution of CD4 + CD25 + regulatory T cells in lymphoid node tissue. METHODS: Totally 22 biopsy and 13 autopsy lymphoid node tissues from HIV-positive patients were examined under microscopy and pathological staging was performed. Specific marker for CD4 + CD25 + regulatory T cells in lymphoid node tissue was detected with anti-Foxp3 monoclonal antibody by immunohistochemistry. RESULTS: Among all the 35 specimens, 5, 4, 14, and 12 specimens were histopathologically staged from 1 to 4, respectively. FoxP3 were detected in all lymphoid node tissues. The distribution of FoxP3-positive lymphocytes were mainly in intermediate zone of follicle and cortical area in stages 1 and 2. The counts of FoxP3-positive lymphocytes remarkably decreased in stages 3 and 4, following depletion of lymphocytes. CONCLUSIONS: CD4 + CD25 + regulatory T cells exist in lymphoid node tissue of patients with HIV infection. Their amounts decrease or deplete along with the progression of AIDS-related lymphadenopathy.

[A pathological study on liver tissues of patients with HIV infection].

OBJECTIVE: To study the pathological changes of the liver tissues of patients with HIV infection. METHODS: 14 biopsy and 12 autopsy liver tissues were examined histologically. HIV-1 related antigen of outer membrane protein gp120 and capsid protein p24 were examined with their corresponding monoclonal antibodies by immunohistochemistry. RESULTS: In the biopsy group, cytomegalic virus (CMV) infection was found in one (1/14) case, outer membrane protein gp120 and/or capsid protein p24 antigen were detected in Kupffer cells and in some of the lymphocytes in 11 cases. All the hepatocytes were negative for outer membrane protein gp120 and capsid protein p24 antigens. In the autopsy group, there were 5 (5/12) cases of liver tissues with CMV infection and 5 cases each with mycobacterium and Toxoplasma gondii infection. Capsid protein p24 was detected in liver tissues in 3 cases. CONCLUSION: There is HIV infection in liver tissue of patients with HIV. The rate of opportunistic infections in liver biopsy samples was lower than that in the autopsy liver tissues of patients with HIV.