Recent progress in the effect of ferroptosis of HSCs on the development of liver fibrosis.

Fibrosis is a common pathological process that must take place for multiple chronic liver diseases to develop into cirrhosis and liver cancer. Liver fibrosis (LF) is regulated by various cytokines and signaling pathways in its occurrence and development. Ferroptosis is an important mode of cell death caused by iron-dependent oxidative damage and is regulated by iron metabolism and lipid peroxidation signaling pathways. In recent years, numerous studies have shown that ferroptosis is closely related to LF. As the main material secreted by the extracellular matrix, hepatic stellate cells (HSCs) are a general concern in the development of LF. Therefore, targeting HSC ferroptosis against LF is crucial. This review describes the current status of treating LF by inducing HSC ferroptosis that would aid studies in better understanding the current knowledge on ferroptosis in HSCs and the future research direction in this field.

Highly Invasive and Metastatic High-grade Endometrial Stromal Sarcoma With BCOR Gene Alterations: A Case Report.

BACKGROUND: The coexistence of a uterine leiomyosarcoma and a high-grade endometrial stromal sarcoma (HGESS) is extremely rare, especially when one of the components causes metastasis. CASE REPORT: A 46-year-old female with aggravated abdominal pain for more than 4 months was diagnosed with uterine malignant mesenchymal tumor composed of predominantly a leiomyosarcoma (99%) and a minor component of HGESS with BCL6 corepressor (BCOR) gene alterations (1%), with ovarian and pelvic metastases. RESULTS: The volume of HGESS with BCOR gene alterations accounted for less than 1% of the tumor mass but caused ovarian and pelvic metastases. CONCLUSION: HGESS with BCOR gene alterations is extremely aggressive. We suggest that when both components of HGESS with BCOR gene alterations and uterine leiomyosarcoma are present in one patient, the HGESS with BCOR gene alterations needs to be highlighted in the pathological report, even if it accounts for less than 1% of the tumor volume.

Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas.

BACKGROUND AND OBJECTIVE: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood. METHODS: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II-IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry. RESULTS: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis. CONCLUSION: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.

Combined large cell neuroendocrine carcinoma of the lung associated with low-grade fetal adenocarcinoma without ß-catenin mutation: a case report.

We report a case of combined large cell neuroendocrine carcinoma of the lung associated with low-grade fetal adenocarcinoma (L-FLAC) without ß-catenin mutation in exon 3. A 33-year-old man presented at the hospital with a more than 5-month history of cough with no obvious cause. Computed tomography revealed a large, solid, round mass located in the upper lobe of the right lung. Microscopic examination showed two tumor components: large cell neuroendocrine carcinoma and low-grade fetal adenocarcinoma. Immunohistochemistry ofthe fetal adenocarcinoma showed abnormal nuclear/cytoplasmic expression of ß-catenin, but no exon 3 mutation in ß-catenin. Our findings provide further insight into the pathologic mechanism of FLAC.

Dendritic fibromyxolipoma of the parotid gland: a case report and review of the literature.

Dendritic fibromyxolipoma, a rare subtype of lipoma, mainly occurs in the neck, back, and chest wall. Here, we describe the first reported case located in the parotid gland. It happened in a 24-year-old woman with a well-demarcated painless mass. Pathologically, the tumor was characterized by small spindle and stellate cells, an unequal number of mature fat cells, plentiful myxoid stroma, and collagenous fiber bundles. Immunochemistry demonstrated that the tumor cells were positive for vimentin, CD34, Bcl-2, and desmin, but not for keratin, EMA, SMA, or S-100. The tumor was successfully removed without complications. This report will bring to the attention of clinicians the clinical features and differential diagnosis of this unusual tumor.

HER-2 status and its clinicopathologic significance in breast cancer in patients from southwest China: re-evaluation of correlation between results from FISH and IHC.

This study aimed to re-evaluate the concordance between FISH and IHC for HER-2 status, and evaluate its clinicopathologic significance in breast cancer by the new guideline (2014) in China. We determined the HER-2 status in 589 cases of invasive breast cancer, the concordance and correlation between these two results and their relationship to cliniopathological characteristics were evaluated. The rate of HER-2 gene amplification identified by FISH was 31.07% (183/589). Concordance was detected in 93.67% with IHC 0/+, 32.26% in IHC 2+, and 61.16% in IHC 3+. The concordance of 54.67% was observed with a Kappa coefficient of 0.189 (P = 0.000), and a positive correlation was found between IHC and FISH (r = 0.427, P = 0.000). Moreover, the expression of ER was negatively correlated with HER-2 gene amplification and the expression of Her-2/neu protein (r = -0.419, P < 0.001; r = -0.144, P < 0.001; respectively), and the PR expression and ER/PR status was negatively correlated with HER-2 gene amplification (r = -0.226, P < 0.001; r = -0.258, P < 0.001), but not significantly with Her-2/neu expression. Interestingly, the tumor size and histological grade were positive correlation with HER-2/neu protein expression. The coincidently positive rate between FISH and IHC in breast cancer is very high, IHC score 0/+ is strongly consistent with HER-2 gene amplification, IHC score 2+~3+ is a preferred method to detect the HER-2 gene status, FISH still remains a standard method of evaluation of the HER-2 gene amplification.

HLJ1 is a novel biomarker for colorectal carcinoma progression and overall patient survival.

The implication of HLJ1, a member of the heat shock protein-40 chaperone family, in colorectal carcinoma (CRC) remains unclear. The aim of this study was to determine the dynamic changes of HLJ1 in CRC both in vitro and in vivo, and the relationship between its level and the survival rate of CRC patients. Both real-time RT-PCR and Western blot were used to detect the expression of HLJ1 in CRC cells, while the distribution of HLJ1 in CRC and its adjacent normal mucosa tissues from CRC patients was determined with immunohistochemistry. Moreover, MTT and in vitro invasive assays were performed to determine the effect of HLJ1 overexpression on cell proliferation and invasion of CRC cells. The results indicated that in highly metastatic CRC cells, the HLJ1 expression was lower than that in lowly metastatic ones, and that the overexpression of HLJ1 significantly inhibited CRC cell proliferation and invasion in vitro. Interestingly, the HLJ1 expression was significantly down-regulated in CRC or lymphatic metastatic tissues from patient, compared to that in the normal mucosa (P<0.05), and the HLJ1 expression was correlated strongly with lymph metastasis, Dukes' stage, and remote metastasis (P<0.05). Most surprisingly, patients with a higher HLJ1 level had a better overall survival rate, compared to that in patients with lower HLJ1 level (P<0.05). Based on all these findings, we conclude that HLJ1 is a strong tumor suppressor for CRC, and thus the down-regulation of the HLJ1 expression may be used as a biomarker to predict clinical outcome of patients with CRC.