[Breast cancer subtypes based on ER/PR and Her2 expression: comparison of MR imaging features].

OBJECTIVE: To evaluate the magnetic resonance (MR) imaging findings of breast cancer subtypes based on the profiles of ER/PR and Her2. METHODS: A retrospective study was conducted for 267 breast cancer subjects between February 2007 and January 2011. Clinicopathologic features and MR imaging findings of four subtypes were compared. The Chi-square (χ(2)) test, Fisher's exact test and χ(2) section method were employed for categorical variables. RESULTS: MR imaging findings:Patients with segment or linear enhancement type accounted for 25.6% in ER/PR(+), Her2(+) subtype group and 36.1% in ER/PR(-), Her2(+) subtype, no significant difference existed between them (χ(2) = 1.112, P = 0.641). But they were significantly higher than ER/PR(+), Her2(-) subtype group and ER/PR(-), Her2(-) subtype group (χ(2) = 32.793, P < 0.001; χ(2) = 14.565, P < 0.001). ER/PR(-), Her2(-) subtype patients accounted for 14.6% of the total breast cancer patients (39/267). Subjects with ER/PR(-), Her2(-) subtype were more likely to present unifocal (91.7%, 33/36) and mass type lesion (92.3%, 36/39). The mass type lesions in ER/PR(-), Her2(-) subtype group were more likely to showed smooth margin [58.3% (21/36), P < 0.001], very high intratumoral signal and peripheral hyperintense pattern on fat suppression T2-weighted imaging (P < 0.001) and early rim enhancement [81.5% (29/36), P < 0.001]. No significantly difference of four subtypes were found on number of mass, mass shape and pattern at dynamic enhancement imaging (χ(2) = 1.413, P = 0.713; χ(2) = 8.423, P = 0.204; χ(2) = 4.657, P = 0.540). CONCLUSION: Segment or linear enhancement type is characterized by MR imaging. Early rim enhanced mass is ER/PR(-), Her2(-) breast cancer. The most important characteristics of MR imaging include a smooth edge of breast mass, very high intratumoral signal on fat suppression T2-weighted imaging and peripheral hyperintense pattern.

Identification of CDT1 as a prognostic marker in human lung adenocarcinoma using bioinformatics approaches.

Background: Lung cancer has the highest cancer-related mortality worldwide. Lung adenocarcinoma (LUAD) is the most common histological subtype of non-small cell lung cancer (NSCLC). Chromatin licensing and DNA replication factor 1 (CDT1), a key regulator of cell cycle control and replication in eukaryotic cells, has been implicated in various cancer-related processes. Given its significant role in cancer, the focus on CDT1 in this study is justified as it holds promise as a potential biomarker or therapeutic target for cancer treatment. However, its prognostic value in lung adenocarcinoma (LUAD) remains unclear. Methods: Bioinformatics analysis was conducted using data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to predict biological processes and signaling pathways, respectively. The LinkedOmics database was employed to identify differentially expressed genes (DEGs) associated with CDT1. Nomograms and Kaplan-Meier plots were generated to assess the survival rates of patients with lung adenocarcinoma (LUAD). To determine the RNA and protein expression levels of CDT1 in LUAD and adjacent normal tissues, quantitative polymerase chain reaction (qPCR) and immunohistochemistry techniques were employed, respectively. Results: CDT1 was upregulated in the vast majority of cancer tissues, based on pan-cancer analysis in TCGA and GEO datasets, as to lung cancer, the level of CDT1 expression was much higher in LUAD tissue than in healthy lung tissue. Our clinical data supported these findings. In our study, we used a specific cutoff value to dichotomize the patient samples into high and low CDT1 expression groups. The Kaplan-Meier survival curve revealed poor survival rates in CDT1 high expression group than the low expression group. To determine if CDT1 expression was an independent risk factor in LUAD patients, univariate and multivariate Cox regression analyses were performed. The result showed that CDT1 was a potential novel prognosis factor for LUAD patients, whose prognosis was poorer when CDT1 expression was higher. Based on functional enrichment analysis, highly expressed DEGs of CDT1-high patients were predicted to be involved in the cell cycle. According to our analysis of immune infiltration, CDT1 exhibited a strong correlation with specific immune cell subsets and was found to be a significant predictor of poor survival in patients with LUAD. Conclusions: Our research found that CDT1 was upregulated in LUAD and that high CDT1 expression predicted poor prognosis. We comprehensively and systematically analyzed the expression level in the datasets as well as in our own clinical samples, we also evaluated the prognostic and diagnostic value of CDT1, and finally, the potential mechanisms of CDT1 in the progression of LUAD. These results suggested that CDT1 may be a prognostic marker and therapeutic target for LUAD.

Long-Term Survival of a Lynch Syndrome Patient With Eight Primary Tumors: A Case Report.

With the modern technological developments in the diagnosis and treatment of cancer, the survival rate of cancer patients has increased. On the other hand, the incidence of multiple primary tumors is increasing annually. Lynch syndrome (LS), an autosomal dominant disorder with germline mutations in DNA mismatch repair genes, increases the risk of cancer in patients carrying those mutations. In this report, we present an extremely rare case of an 81-year-old male patient with eight primary malignancies and LS. The patient is still alive having survived for more than 41 years since the initial discovery of the first tumor. The eighth and most recently diagnosed primary cancer was a malignant peripheral nerve sheath tumor. Although there have been numerous reports of malignancies in LS, malignant peripheral nerve sheath tumors have not been reported previously with LS. Here, we report, to the best of our knowledge, the first case of a malignant peripheral nerve sheath tumor with LS.

[Clinicopathologic study on 61 cases of uterine papillary serous carcinoma with or without adjuvant therapy].

OBJECTIVE: To study the clinicopathologic features of uterine papillary serous carcinoma (UPSC) and the roles of adjuvant therapy. METHODS: Sixty-one cases of UPSC with operation done and followed up for a period of 4 to 9 years were enrolled into the study. The histology of slides specimens were reviewed and immunohistochemical study was performed. The follow-up and survival data were analyzed. RESULTS: All of the 61 patients were post-menopausal, with a median age of 68 years. The clinical presentations included abnormal vaginal bleeding, abdominal symptoms and abnormal Pap smears. The median size of the tumors was 7.5 cm (range=1.2 to 14.8 cm). There were 27.9% cases in FIGO stage I (8.2% in stage IA, 14.8% in stage IB and 4.9% in stage IC), 9.8% in stage II, 32.8% in stage III and 29.5% in FIGO stage IV. The histologic features were similar to those of the ovarian counterpart, with tumor cells containing the high-grade nuclei and arranged in complex papillae. Psammoma bodies were identified in 24.6% of the cases. Immunohistochemical study showed that the tumor cells demonstrated diffuse and strong nuclear staining for p53 and Ki-67. They were negative for estrogen receptor and progesterone receptor. Fifteen of the 61 cases (24.6%) showed no evidence of myometrial invasion. However, ten of the 15 cases had extrauterine disease, with peritoneal (6/15) and nodal (9/15) involvement. Tumors with deep myometrial invasion, lymphovascular permeation and nodal metastasis were associated with worse prognosis by univariate analysis. Fifty-six patients received adjuvant therapy. The number of patients receiving adjuvant chemotherapy alone, adjuvant radiotherapy alone and combined adjuvant chemotherapy/radiotherapy were 42, 24 and 10, respectively. The median survivals of the chemotherapy group and non-chemotherapy group (with or without radiotherapy) were 66.4 months and 32.8 months, respectively. CONCLUSIONS: UPSC has distinctive clinical and pathologic features. The tumor stage, lymph node status, lymphovascular permeation and depth of myometrial invasion were important prognostic factors. Adjuvant chemotherapy for stage III/IV tumors or recurrent UPSC may have survival benefit.

Paraffin-embedded Tissue Fragment Suspension (PETFS): A Novel Method for Quality Control Preparation in Immunohistochemistry.

Immunohistochemistry (IHC) is one of the most important adjunctive techniques in surgical pathology. Quality controls are essential for staining interpretation. The most common controls are cut from the formalin-fixed, paraffin-embedded tissue blocks in advance. In contrast, we developed paraffin-embedded tissue fragment suspension (PETFS), a novel method in liquid form, for quality control preparation. The liquid form controls were cut from the donor formalin-fixed, paraffin-embedded paraffin blocks, stored in the 4°C fridge easily, and added to the top and bottom of the test slide directly by pipetting. The tissue fragments from the PETFS had a comparable IHC staining pattern to that of the control sections from the original donor blocks. Over a 180-day testing period, the IHC staining pattern and intensity remained strong and specific. The clinical value of PETFS method was further validated by their successful application as controls for the expression of estrogen receptor, progesterone receptor, and C-erbB-2 in 240 breast invasive ductal carcinomas. We concluded that PETFS is a fast, low-cost, and less donor tissue consumption robust technique as quality controls for routine IHC staining in surgical pathologic practice.

Role of high mobility group A1 and body mass index in the prognosis of patients with breast cancer.

The high mobility group A1 (HMGA1) protein is associated with poor prognosis in patients with a wide range of cancers. However, the affect of HMGA1 on the risk of mortality from breast cancer (BC) has not been fully characterized. In the present retrospective multiple center study, the HMGA1 expression level was determined by performing immunohistochemistry on surgical tissue samples of 273 BC specimens from the Second Affiliated Hospital of Zhejiang University (Zhejiang, China) and 310 BCs from the National Engineering Center for Biochip (Shanghai, China). Kaplan-Meier analysis and Cox proportional hazard model were employed to analyze the survivability. HMGA1 expression was significantly associated with tumor histological degree and body mass index (BMI). However, HMGA1 expression showed no prognostic value in patients with BC. Combined evaluation of HMGA1 expression and high BMI (≥24 kg/m2) predicted worse overall survival of BC. Therefore, HMGA1 and BMI were considered to serve synergistic roles in the development and progression of BC, and combined evaluation of HMGA1 expression and high BMI may be an effective marker in predicting poor prognosis of BC patients.

Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer.

High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage II-III, low pathological grade and non-triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors.

Features of intestinal T-cell lymphomas in Chinese population without evidence of celiac disease and their close association with Epstein-Barr virus infection.

BACKGROUND: Intestinal T-cell lymphoma (ITCL) is a heterogeneous lymphoid neoplastic group with variable clinical and pathological features. ITCL in oriental countries is different from enteropathy-type intestinal T-cell lymphoma (ETCL) in relation to celiac disease and Epstein-Barr virus (EBV). The objective of this study was to investigate the clinicopathological features, immunophenotype, expression of cytotoxic molecule (TIA-1), T-cell receptor (TCR)-gamma gene rearrangement, and Epstein-Barr virus (EBV) latent infection in primary ITCL without celiac disease in Chinese. METHODS: The clinical data of 42 patients were analyzed, and the patients were followed up. Compared with human reactive lymphoid tissues, in situ hybridization for EBER1/2, polymerase chain reaction for TCR-gamma gene rearrangement, and immunohistochemical staining for immunophenotypes, TIA-1 and EBV latent membrane proteins (LMP-1) were investigated. Survival curves of different clinicopathological features, immuno-phenotypes, expression of LMP1, TCR-gamma gene rearrangement and therapy were analyzed. RESULTS: Three fourths of the patients suffered from ITCL in China were men with a peak age incidence in the 4th decade. Common presenting features included fever and hemotochezia. The prognosis was poor with a median survival of 3.0 months. The lesions were mostly localized in the ileocecum and colon. About 38/42 (90.5%) patients demonstrated pleomorphic medium-sized on large cells. Histological features of celiac disease were rarely seen. All 42 patients with ITCL revealed CD45RO positive. Neoplastic cells partially expressed T-cell differentiated antigens (CD3epsilon, CD4, CD8) and NK cell associated antigen (CD56). The positive frequency of CD3epsilon, CD4, CD8 and CD56 was 28/42 (66.7%), 7/42 (16.7%), 10/42 (23.8%) and 12/42 (28.6%) respectively. Thirty-nine cells (92.9%) expressed TIA-1, but none expressed CD20 and CD68. More than half of the patients (64.3%, 64.3% and 59.5%) revealed TCR-gamma gene rearrangement by three different TCR-gamma primers respectively. EBER1/2 was detected in 41 (97.6%) of the 42 patients. The expression frequency of LMP-1 was 38.1% (16/42). CONCLUSIONS: Primary ITCL without celiac disease in Chinese is a special highly EBV-associated clinicopathological entity. There are few similarities in patients with celiac disease in western countries. A small proportion of primary ITCLs in Chinese and extranodal NK/T-cell lymphoma of nasal type belong to the same spectrum.

Influence of N,N'-diacetyl-L-cystine on D-galactosamine/lipopolysaccharide induced immunological liver failure in mice.

AIM: To study the therapeutic effects of N,N'-diacetyl-L-cystine (DiNAC) on immunological liver failure. METHODS: Serum ALT, AST and T cell subsets in peripheral blood of the experimental animals during the trial period were analyzed by an automatic serum analyzer and a flow cytometer, respectively. The sectioned liver specimens were examined under a light microscope. And 24 h after the injection of Gal/LPS, the survival rate of rats was calculated. RESULTS: DiNAC (50, 200, 800 mg x kg(-1), i.p.) suppressed the elevation of serum levels of ALT and AST, markedly enhanced proliferation and differentiation of T cell subsets (CD4+, CD8+ and Th1, Th2), and improved all the histopathological features. In mice of fulminant hepatic failure (FHF), the survival time significantly prolonged and the survival rate increased 24 h after i.p. DiNAC. These effects were obviously dose-dependent. CONCLUSION: DiNAC on mice with FHF has an inhibitory action which is related to immune mechanism.

[Analyzing of prognosis of intestinal T-cell lymphoma].

OBJECTIVE: To investigate the roles of different clinicopathological features and expression of EBV genome in prognosis of intestinal T-cell lymphoma (ITCL). METHODS: Polymerase chain reaction for TCR-gamma gene rearrangement, in situ hybridization for EBER1/2 and immunohistochemical staining for CD4, CD8, CD45RO, CD56, TIA-1 were investigated and all patients followed-up. The LMP-1 expression was determined in forty-two ITCLs cases. The relationship between clinical data, different clinicopathological features, expression of EBV genome and prognosis were analyzed by SPSS10.0 program. RESULTS: (1) All 42 cases of ITCL had an extremely poor prognosis with a median survival of 3.0 months, of which the one year survival rate and two year survival rate being 30% and 22% respectively. (2) The patients without TCR-gamma gene rearrangements showed poorer prognosis than those with TCR-gamma gene rearrangements, and the patients who received operation and chemotherapy showed better prognosis than those who only received operation (P < 0.05). (3) No significant prognostic factor for ITCLs was determined. CONCLUSION: The special clinicopathological features of ITCL could be due to the cytotoxic function and the role of EBV infection in the pathogenesis of ITCL.