Humans ; Biomarkers, Tumor/metabolism* ; Claudins/analysis* ; Consensus ; Immunohistochemistry/methods* ; Stomach Neoplasms/diagnosis*

BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM_2.5 and PM₁₀, carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM_2.5 (8.53 µg/m³) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM_2.5 and survival time to newly onset depressive disorder. CONCLUSION PM_2.5 is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1.
Humans ; Particulate Matter/analysis* ; Male ; Female ; Middle Aged ; Longitudinal Studies ; Aged ; Incidence ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Taiwan/epidemiology* ; Receptors, Tumor Necrosis Factor, Type I/blood* ; Proportional Hazards Models ; Biomarkers/blood* ; Depression/epidemiology* ; Aged, 80 and over ; Depressive Disorder/chemically induced* ; Risk Factors ; Air Pollution/adverse effects*

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ²=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ²=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ² =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ²=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/diagnosis* ; alpha-Fetoproteins/analysis* ; Biomarkers, Tumor ; Glypicans ; Ascites ; Venous Thromboembolism ; Peritoneal Neoplasms ; Liver Cirrhosis

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.
Male ; Humans ; Female ; Biomarkers, Tumor/analysis* ; Gastrointestinal Neoplasms/pathology* ; S100 Proteins/analysis* ; Melanoma

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Desmin/analysis* ; China ; Lipoma/pathology* ; Fibroblasts/pathology* ; S100 Proteins/analysis* ; Diagnosis, Differential ; Fibrocartilage/pathology* ; Biomarkers, Tumor/analysis*

Objective: To investigate the clinicopathological features, immunophenotype, molecular features and differential diagnosis of primary synovial sarcoma of the lung (PSSL). Methods: Twelve cases of PSSL were collected at Henan Provincial People's Hospital, during May 2010 and April 2021, and their clinicopathological parameters were summarized. SS18-SSX, H3K27Me3, and SOX2 were added to the original immunomarkers to evaluate their diagnostic value for PSSL. Results: The age of 12 patients when diagnosed ranged from 32 to 75 years (mean of 50 years). There were 7 males and 5 females, 2 left lung cases and 10 right lung cases. Of the 6 patients who underwent surgical resection, five cases were confined to lung tissue (T1), one case had mediastinal invasion (T3), two cases had regional lymph node metastasis (N1), and none had distal metastasis. Microscopically, 11 cases showed monophasic spindle cell type and one case showed biphasic type composed of mainly epithelial cells consisting of cuboidal to columnar cells with glandular and cribriform structures. It was difficult to make the diagnosis by using the biopsy specimens. Immunohistochemistry (IHC) showed CKpan expression in 8 of 12 cases; EMA expression in 11 of 12 case; TLE1 expression in 8 of 12 cases; S-100 protein expression in two of 12 cases; various expression of bcl-2 and vimentin in 12 cases, but no expression of SOX10 and CD34 in all the cases. The Ki-67 index was 15%-30%. The expression of SS18-SSX fusion antibody was diffusely and strongly positive in all 12 cases. SOX2 was partially or diffusely expressed in 8 of 12 cases, with strong expression in the epithelial component. H3K27Me3 was absent in 3 of 12 cases. SS18 gene translocation was confirmed by fluorescence in situ hybridization (FISH) test in all 12 samples. Six cases underwent surgery and postoperative chemotherapy, while the other six cases had chemotherapy alone. Ten patients were followed up after 9-114 months, with an average of 41 months and a median of 26 months. Five patients survived and five died of the disease within two years. Conclusions: PSSL is rare and has a broad morphological spectrum. IHC and molecular tests are needed for definitive diagnosis. Compared with current commonly used IHC markers, SS18-SSX fusion antibody has better sensitivity to PSSL, which could be used as an alternative for FISH, reverse transcription-polymerase chain reaction or next generation sequencing in the diagnosis of PSSL.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Biomarkers, Tumor/analysis* ; Sarcoma, Synovial/diagnosis* ; In Situ Hybridization, Fluorescence ; Histones/genetics* ; Proto-Oncogene Proteins/metabolism* ; Oncogene Proteins, Fusion/genetics* ; Repressor Proteins/metabolism* ; Lung/pathology* ; Lung Neoplasms

Objective: To investigate the clinicopathological features of perivascular epithelioid cell tumor (PEComa) of the lung. Methods: Eight PEComa cases of the lung diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China from July 2008 to December 2021 were collected and subject to immunohistochemical staining, fluorescence in situ hybridization and next generation sequencing. The relevant literature was reviewed and the clinicopathological features were analyzed. Results: There were 5 males and 3 females, aged from 18 to 70 years (mean 39 years). There were 3 cases of the right upper lung, 3 cases of the left lower lung, 1 case of the left upper lung and 1 case of the right middle lung. Seven cases were solitary and 1 case was multifocal (4 lesions). Seven cases were benign while one was malignant. The tumors were all located in the peripheral part of the lung, with a maximum diameter of 0.2-4.0 cm. Grossly, they were oval and well circumscribed. Microscopically, the tumor cells were oval, short spindle-shaped, arranged in solid nests, acinar or hemangiopericytoma-like patterns, with clear or eosinophilic cytoplasm. The stroma was rich in blood vessels with hyalinization. Coagulated necrosis and high-grade nuclei were seen in the malignant case, and calcification was seen in 2 cases. Immunohistochemically, the tumor cells were positive for Melan A (8/8), HMB45 (7/8), CD34 (6/8), TFE3 (4/7), and SMA (3/8). All cases were negative for CKpan and S-100. TFE3 (Xp11.2) gene fusion was examined using the TFE3 break-apart fluorescence in situ hybridization in 5 cases, in which only the malignant case was positive. The next generation sequencing revealed the SFPQ-TFE3 [t(X;1)(p11.2;p34)] fusion. Follow-up of the patients ranged from 12 to 173 months while one patient was lost to the follow-up. The malignant case had tumor metastasis to the brain 4 years after the operation and then received radiotherapy. Other 6 cases had no recurrence and metastasis, and all the 7 patients survived. Conclusions: Most of the PEComas of the lung are benign. When there are malignant morphological features such as necrosis, high-grade nuclei or SFPQ-TFE3 gene fusion, close follow-up seems necessary.
Male ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Perivascular Epithelioid Cell Neoplasms/pathology* ; Lung/pathology* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Necrosis ; Biomarkers, Tumor/analysis*

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.
Female ; Humans ; Middle Aged ; Adult ; Aged ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections ; China ; Adenocarcinoma/pathology* ; Endometrium/pathology* ; Gastrointestinal Neoplasms/pathology* ; Biomarkers, Tumor/analysis*

Objective: To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma (PCAS), and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS. Methods: Thirteen cases of PCAS were collected at Beijing Anzhen Hospital, Capital Medical University from January 2007 to December 2021. The clinicopathological features, diagnosis, differential diagnosis and outcome were retrospectively analyzed. KDR mutation was detected by next-generation sequencing (NGS) and then the expression of KDR (VEGFR2) was determined by immunohistochemistry (IHC), with review of relevant literatures. Results: There were eight males and five females with a mean age of 45 years. The primary tumor was in the right atrium in 10 cases, left atrium in two cases and right ventricle in one case. The histomorphology was mainly poorly differentiated angiosarcoma (11 cases), with highly pleomorphic spindle or round cells in solid sheets, brisk mitotic activity and extensive necrosis. Vascular lumen formation was observed in two cases of high to moderate differentiation, and biphenotypic differentiation was seen in five cases. IHC staining showed CD34, CD31, Fli1, ERG and vimentin were diffusely positive, pan-cytokeratin was positive, Ki-67 index ranged from 3% to 90%, which was positively correlated with the differentiation degree and grade of the PCASs (P<0.05). At the end of follow-up period, one patient was alive, two patients were lost to follow-up, and the remaining 10 patients had an average survival time of 4.6 months. Finally, NGS sequencing was performed on seven samples after screening, and the results showed that KDR and NF1 mutations were both present in three cases. VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS (P>0.05), and it was not related to KDR mutation. Conclusions: PCASs mainly occur in the right atrium, and are mainly poorly differentiated. Ki-67 index is helpful to assess the degree and grade of tumor differentiation. The occurrence and development of PCAS may be related to the pathway involved in KDR mutation, but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS, and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.
Male ; Female ; Humans ; Middle Aged ; Hemangiosarcoma/genetics* ; Retrospective Studies ; Ki-67 Antigen ; Immunohistochemistry ; Molecular Biology ; Biomarkers, Tumor/analysis*

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.
Humans ; Male ; Female ; Aged ; Adult ; Middle Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/pathology* ; B7-H1 Antigen/metabolism* ; Lung Neoplasms/pathology* ; Retrospective Studies ; China ; Prognosis ; Biomarkers, Tumor/analysis* ; DNA Helicases/genetics* ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*