Genomic characteristics of pancreatic squamous cell carcinoma, an investigation by using high throughput sequencing after in-solution hybrid capture.

Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC. To verify the genomic characteristics of pancreatic SCC, we employed in-solution hybrid capture targeting 137 cancer-related genes accompanied by high throughput sequencing (HTS) to compare the different genetic variants in SCC and AC of pancreas. We compared the genetic alterations of known biomarkers of pancreatic adenocarcinoma in different pancreatic cancer tissues, and identified nine mutated genes in SCC of pancreas: C7orf70, DNHD1, KPRP, MDM4, MUC6, OR51Q1, PTPRD, TCF4, TET2, and nine genes (ABCB1, CSF1R, CYP2C18, FBXW7, ITPA, KIAA0748, SOD2, SULT1A2, ZNF142) that are mutated in pancreatic AC. This study may have taken one step forward on the discovery of potential biomarkers for the targeted treatment of SCC of the pancreas.

Efficacy and prognosis of neoadjuvant chemotherapy is correlated with breast cancer molecular classification.

Breast cancer is one of the most common cancers affecting women globally. Recent studies have begun to investigate the possibility of customized treatment options for individuals based on the specific cancer type. Here, we sought to analyze the relationship between the molecular classification of breast cancer and the efficacy and prognosis of neoadjuvant chemotherapy (NCT). The study included 100 breast cancer patients treated with an NCT regimen of epirubicin and docetaxel (ET) who were divided into groups based on cancer subtype (luminal, HER2 over-expression, and basal-like subtype). The nuclear classification, number of NCT cycles, pathological remission rate, and clinical curative effect, as well as the disease-free survival time (DFS) and the overall survival (OS), were compared across groups. The nuclear grade of participants in the basal-like group was significantly higher than those in the other groups but this group had fewer preoperative NCT cycles and lower pathological remission and clinical efficacy (Z=53.245, 50.077, 62.467, χ2=16.082, p<0.05). The OS and DFS of participants in the luminal subtype group were significantly higher than those in other groups while those in the basal-like subtype group were the lowest. The OS and DFS of participants who achieved pathological complete remission (pCR) through NCT treatment were significantly higher than those of the patients who had not achieved pCR through NCT treatment (χ2=9.558, 10.139, p<0.05). Therefore, we conclude that when NCT (ET regimen) is used in the treatment of breast cancer, the curative effects and prognosis appear to be correlated with the molecular classification of the tumor. Based on these results, clinicians should consider the molecular classification of the individual tumor to design the most effective treatment option.

Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer.

AIM: To evaluate the expression of galectin-1 and vascular endothelial growth factor (VEGF) in gastric cancer and investigate their relationships with clinicopathologic factors and prognostic significance. METHODS: Galectin-1 and VEGF were immunohistochemically investigated in tumor samples obtained from 214 gastric cancer patients with all tumor stages. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on formalin-fixed, paraffin-embedded sections of surgical specimens. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathologic variables, and patient survival were analyzed. All patients underwent follow-up until cancer-related death or more than five years after tumor resection. P values < 0.05 were considered statistically significant. RESULTS: Immunohistochemical staining demonstrated that 138 of 214 gastric cancer samples (64.5%) were positive for galectin-1, and 116 out of 214 gastric cancer samples (54.2%) were positive for VEGF. There was a significant association between galectin-1 and VEGF expression; VEGF was detected in 60.1% of galectin-1-positive samples and 43.4% of galectin-1-negative samples (P < 0.05). Galectin-1 expression was associated with tumor size, tumor location, stage, lymph node metastases, and VEGF expression (all P < 0.05). VEGF expression was related to tumor size, stage, and lymph node metastases (all P < 0.05). The 5-year survival rate was 56.6% for galectin-1-positive patients and 69.2% for galectin-1-negative patients, and the prognosis for galectin-1-positive patients was significantly poorer compared with galectin-1-negative patients (χ² = 13.880, P = 0.000). The 5-year survival rates for VEGF-positive and VEGF-negative patients were 53.4% and 70.5%, respectively (χ² = 4.619, P = 0.032). The overall survival rate of patients with both galectin-1 and VEGF overexpression in gastric cancer tissue samples was significantly poorer than other groups (both P < 0.05). CONCLUSION: Galectin-1 expression was positively associated with VEGF expression. Both galectin-1 and VEGF can serve as independent prognostic indicators of poor survival for gastric cancer after gastrectomy.

[Significance and expression of p53, p21(Cip1/WAF1) and Gadd45α in breast neoplasm tissues].

OBJECTIVE: To explore the expression and significance of p53, p21(Cip1/WAF1) and Gadd45α protein in breast cancer and their correlations with clinicopathologic features and prognosis in breast cancer. METHODS: The expressions of p53, p21(Cip1/WAF1) and Gadd45α proteins were determined by immunohistochemical staining. The relationship between these three proteins and clinicopathologic features in breast cancer was analyzed by χ(2) test and Spearman's rank correlation analysis. And the survival analyses were performed with the Kaplan-Meier method and Cox regression. The differences between the curves were examined with the two-tailed Log-rank test. RESULTS: In 133 cases of invasive breast cancer, the positive rates of p53, p21(Cip1/WAF1) and Gadd45α protein were 58.6%, 47.4% and 41.4% respectively. The expressions of p21(Cip1/WAF1) and p53 in cancer were significantly higher than those in the adjacent mammary gland tissue (P < 0.05) while the expression of Gadd45α was lower than that in the control mammary gland tissue (P < 0.05). The positive rate of p21(Cip1/WAF1) was correlated with the histological stage, local recurrence and positive C-erbB-2. And the positive rate of Gadd45α was correlated with the histological stage, lymph node metastasis, metastasis and positive estrogen receptor/progesterone receptor (ER/PR). The positive rate of p53 was correlated with the lymph node metastasis and TNM stage. Spearman's rank correlation analysis showed that p21(Cip1/WAF1) was correlated positively with p53, p53 negatively with Gadd45α while p21(Cip1/WAF1) had no correlation with Gadd45α. With the follow-up data, Kaplan-Meier analysis showed that p21(Cip1/WAF1), Gadd45α, p53, lymph node metastasis, C-erbB-2 positive and TMN stage were associated with prognosis. Furthermore, Cox stepwise hazard analysis shows that p21(Cip1/WAF1), Gadd45α, C-erbB-2 and TMN stage were correlated with prognosis of breast cancer. Also the Kaplan-Meier analysis showed that p53(+)Gadd45α(-) and p53(+)p21(Cip1/WAF1)(+) were correlated with a poor prognosis of breast cancer. CONCLUSIONS: The expressions of p21(Cip1/WAF1), Gadd45α and p53 are associated with the clinicopathologic features and prognosis in breast cancer. Indicating a poor prognosis of breast cancer, p53(+)Gadd45α(-) and p53(+)p21(Cip1/WAF1)(+) may become independent indices for prognostic evaluations.

Carcinoma of the right side colon accompanied by Sister Mary Joseph's nodule and inguinal nodal metastases: a case report and literature review.

Umbilical metastases from intraperitoneal malignancies are universally referred to Sister Mary Joseph's nodule (SMJN). The most frequent primary tumor sites include the stomach and ovaries. SMJN caused by colon cancer is uncommon. Likewise, carcinoma of the right side colon metastasizing to inguinal lymph nodes is considered almost impossible. To the best of our knowledge, there is no report of right side colon cancer synchronously involving both the umbilicus and inguinal lymph nodes in the literature. We present a case of right side colon cancer (RSCC) metastasizing to the umbilicus and inguinal lymph nodes, which was confirmed by routine pathological evaluation and immuohistochemistry.

Clinical significance of immunohistochemical expression of hypoxia-inducible factor-1alpha as a prognostic marker in rectal adenocarcinoma.

BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha), a subunit of hypoxia-inducible factor-1 (HIF-1), furnishes tumor cells with the means of adapting to stress parameters, such as tumor hypoxia, and promotes critical steps in tumor progression and aggressiveness by inducing angiogenesis and regulating energy metabolism. In this study, we investigated the relationship between HIF-1alpha and vascular endothelial growth factor (VEGF) and clinicopathologic characteristics, and evaluated the role of HIF-1alpha expression in patients with rectal adenocarcinoma. PATIENTS AND METHODS: The immunohistochemical expression of HIF-1alpha and VEGF was evaluated in 30 formalin-fixed, paraffin-embedded postoperative rectal adenocarcinoma tissue samples. Correlations with clinicopathologic characteristics were determined by cross-tabulations. The impact of the immunoreactivity of HIF-1alpha with regard to the overall survival and local control endpoints was determined by univariate analyses. RESULTS: Increased HIF-1alpha expression was strongly associated with VEGF positivity (P = 0.002), Dukes stage (P = 0.017), and lymph node metastasis (P = 0.001). No correlation was found between the level of HIF-1alpha expression and histologic grade (P = 0.63). The Kaplan-Meier curves showed a significantly shorter overall survival (P = 0.0087) and local control (P = 0.0438) for patients with high HIF-1alpha expression. CONCLUSION: These results show that HIF-1alpha might represent an important biologic marker evaluating the prognosis of patients with rectal adenocarcinoma.

Immunosuppressive therapy for 54 children patients with acquired severe aplastic anemia / 中华儿科杂志

<p><b>OBJECTIVE</b>Aplastic anemia is characterized by bone marrow failure and marked reduction of white blood cells, red blood cells and platelets in peripheral blood. Clinical studies have shown that immunosuppressive therapy greatly prolonged the long-term survival of some patients with aplastic anemia. But in severe aplastic anemia (SAA) patients whose ANC was < 0.5 x 10(9)/L, platelets were < 20 x 10(9)/L, very low bone marrow proliferation and high death rate were observed. The present study aimed to evaluate the efficacy of immunosuppressive treatments with cyclosporine A (CSA) alone or CSA combined with antithymocyte globin (ATG) in children with acquired SAA.</p><p><b>METHODS</b>Fifty-four cases with SAA were treated with immunosuppressive agents mentioned above in our department from Jan. 1997 to June 2003, 31 of the cases had treated with CSA combined with ATG. There were 18 cases with SAA type I and 13 cases with SAA type II in CSA combined with ATG group, and 13 cases had very severe aplastic anemia. The other 23 cases were treated with CSA alone (CSA group), 10 of these cases had SAA-I and 13 had SAA-II, and 5 cases had very severe aplastic anemia. The responsive rate, relapse, adverse reactions and event free survival (EFS) were compared between CSA combined with ATG group and CSA group.</p><p><b>RESULTS</b>The proportions of patients with different types of the disease and severity were comparable between the two groups. The responsive time of the CSA combined with ATG group and CSA group was 2.5 months and 3.5 months, respectively (P < 0.05), the responsive rate in two groups was 81% (25/31) and 52% (12/23), respectively (chi(2) = 4.962, P < 0.05). In 37 cases who were responsive to therapy, the relapse rate was 8% (2/25) and 50% (6/12) respectively (chi(C)(2) = 6.143, P < 0.05). There were no significant differences in adverse reactions to the immunosuppressive agents. All cases were followed-up for more than 1 year, and the event-free survival over one year in these two groups was 81% (25/31) and 52% (12/23), respectively. Forty-seven cases were followed-up for more than two years, and the event-free survival was 74% (20/27) and 50% (10/20), respectively (P < 0.01). Twelve cases were followed-up for over 5 years. There were no secondary tumor, myelodysplastic syndrome and other colony diseases.</p><p><b>CONCLUSION</b>The immunosuppressive therapies for acquired severe aplastic anemia in childhood were effective. The effect of CSA combined with ATG was better than that of CSA alone, and the relapse rate was lower with the combined treatment. However, the long-term effect needs longer follow-up studies to evaluate.</p>

[Expression and significance of CD44v6, bcl-2, and vascular endothelial growth factor(VEGF) in endometrial adenocarcinoma].

BACKGROUND & OBJECTIVE: The pathogenesis of endometrial carcinoma has not been clear yet. The aim of this study was to investigate the influence of expression of CD44v6, bcl-2, and vascular endothelial growth factor (VEGF) on oncogenesis and progression in endometrial carcinoma. METHODS: The expression levels of CD44v6, bcl-2, and VEGF were determined using immunohistochemistry in 55 cases with endometrial adenocarcinoma, 10 cases each of normal proliferative endometrium, simple hyperplasia, and atypical hyperplasia, respectively. RESULTS: (1)The expression of CD44v6 and VEGF increased gradually from normal proliferative endometrium to simple hyperplasia, atypical hyperplasia,and adenocarcinoma, which showed highly significant difference (P< 0.001, P< 0.001), whose ratios were 10%, 40%, 60%, 78.18% and 0%, 0%, 10%, 83.64%,respectively. While the expression of bcl-2 showed no significant difference among the above different tissues. (2)The CD44v6 expression in endometrial carcinoma was inversely associated with surgical stages and lymph node metastasis(P< 0.05, P< 0.01). The bcl-2 expression was found to be significantly related to histologic grades of the tumor (P< 0.05). The VEGF expression was significantly associated with surgical stages, myometrial invasion, and lymph node status. (3)There was statistically significant correlation between bcl-2 and CD44v6, bcl-2 and VEGF expression (P< 0.05, P< 0.05). (4)The univariate analysis revealed that the expression of CD44v6 and bcl-2 were significantly related to the prognosis of the patients (P< 0.01, P< 0.05). Cox proportional hazards model analysis showed that the prognosis was independently affected by age, surgical stage, and CD44v6 expression. CONCLUSION: CD44v6, bcl-2, and VEGF play roles in oncogenesis and progression of endometrial adenocarcinoma. Detection of these gene proteins may be helpful for early diagnosis, prognosis prediction, and treatment of endometrial carcinoma.

Diagnostic values of serum levels of HA, PC III, C IV and LN to the liver fibrosis in children with beta-thalassemia major / 中华儿科杂志

<p><b>OBJECTIVE</b>The presence of liver fibrosis in patients with beta-thalassemia major has been demonstrated to be an important negative prognostic factor. Identification of liver fibrosis in early stage would be of great value. Hyaluronic acid (HA), type III pre-collagen (PC III), collagen IV (C IV) and laminin (LN) as serum markers were widely used in the diagnosis of liver fibrosis in patients with chronic viral infections or alcoholic liver diseases. However, their values in thalassemic liver fibrosis have not been studied. This work was to determine the serum HA, PC III, C IV and LN levels in children with beta-thalassemia major and evaluate the diagnostic utility.</p><p><b>METHOD</b>Serum HA, PC III, C IV and LN in 49 hospitalized children with beta-thalassemia major (aged 1 - 15 years with the media age of 6.27 years) and 41 healthy children served as controls (aged 1 - 13 years with media age of 6.40 years) were detected by radioimmunoassay (RIA). Forty-five of 49 cases were performed percutaneous liver biopsies, and the histopathological fibrosis was compared with the four serum markers. The correlation and discriminate analysis were used.</p><p><b>RESULTS</b>All the serum levels of HA, PC III, C IV and LN in beta-thalassemia were significantly higher than those in controls (P < 0.01). In 36 of 45 cases, the histopathology showed liver fibrosis including stage I and stage II by biopsies with a positive rate of 80%. The serum levels of four markers increased successively with the aggravation of liver fibrosis from stage 0 to stage II, and significant correlation was observed between the level of HA or PC III and the stage of fibrosis (HA, r = 0.379, P = 0.017; PC III, r = 0.455, P = 0.04). While there was no difference between the level of C IV or LN and fibrosis (C IV, r = 0.312, P = 0.053; LN, r = 0.310, P = 0.055). Using discriminate analysis, the discriminate function of co-detection of the four markers for the diagnosis of fibrosis was 0.002 HA + 0.003 PC III + 0.002 C IV + 0.006 LN-1.859, which had a sensitivity of 93.88%, specificity of 68.29%, predictive value of positive test and negative test of 77.97% and 90.32%, respectively. Moreover, there was a significant correlation between the serum level of HA or PC III and the liver iron concentration (HA, r = 0.318, P = 0.035; PC III, r = 0.305, P = 0.044).</p><p><b>CONCLUSION</b>The results suggest that, in beta-thalassemia major with chronic liver disease, HA and PC III showed more practical value in diagnosing liver fibrosis than the levels of C IV and LN. The combination of the four serum markers could improve the accuracy and reliability of the diagnosis. A validation study is necessary before introducing into the prediction function during the clinical practice.</p>