Sheau-Fang Yang

Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma

Background: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established. Aim: To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development. Methods: Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival. Results: A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan–Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups. Conclusions: The results showed that p-STAT3 (tyr705) expression was closely correlated with histological grading and intratumour MVD in HCC. Thus, the potential role of p-STAT3 (tyr705) in HCC development may be through these correlations.

Potential role of leptin expression in hepatocellular carcinoma

Background: Obesity is associated with hepatocellular carcinoma (HCC). The association may result from the aberrant expression of adipokines. Aim: To explore the potential biological effect and prognostic value of leptin, one of the adipokines, in HCC. Methods: Immunohistochemistry was used to evaluate the expression of leptin in 68 patients with HCC. The expression of Ki-67 and microvessel density (MVD) of tumorous lesions in HCC were also analysed. The result of leptin expression was further correlated with Ki-67 expression, intratumour MVD, clinicopathological characteristics, overall survival and the postoperative use of medroxyprogesterone acetate (MPA). Results: High leptin expression was seen in 60.3% of patients with HCC and was significantly correlated with intratumour MVD (high v low; 59.2 (standard deviation 3.2) v 44.2 (19.5), p = 0.004), but not with Ki-67 expression. No marked correlation was seen between leptin expression and clinicopathological characteristics. However, using a multivariate Cox’s proportional hazards model, leptin expression was a predictor for improved overall survival of patients with HCC (odds ratio 0.16; 95% confidence interval 0.03 to 0.87; p = 0.033). In addition, the Kaplan–Meier survival curve showed that high leptin expression was associated with a better survival in patients with HCC, treated postoperatively with MPA (p = 0.008, log rank test). Conclusion: High leptin expression was associated with an increased intratumour MVD and thus may be associated with HCC development. In addition, high leptin expression was a predictor for improved survival of patients with HCC, treated postoperatively with MPA.

Potential prognostic value of leptin receptor in hepatocellular carcinoma

Background: Obesity is associated with several human malignancies, including hepatocellular carcinoma (HCC). This association may result from the deregulated expression of adipokines. Aims: To explore the potential role and the prognostic value of leptin receptor (Ob-R) in HCC. Methods: 66 patients with pathologically confirmed HCC were included in this study. Immunohistochemistry was used to evaluate the expression of Ob-R, microvessel density (MVD) and Ki-67 index in these patients. Eventually, the profiles of Ob-R expression, obtained by a semiquantitative scoring system, were further correlated with Ki-67 expression, intratumour MVD, clinicopathological characteristics and overall survival. Results: High Ob-R expression was seen in 53% of patients with HCC and was significantly correlated with intratumour MVD (high v low; 59.4 ?3.2) v 44.7 ?3.7); p = 0.004), but not with Ki-67 expression. In addition, Ob-R expression was inversely correlated with vascular invasion (p = 0.037), but not with other known clinicopathological characteristics. The Kaplan–Meier survival curve showed that high Ob-R expression was associated with a better overall survival (p = 0.027). Meanwhile, multivariate analysis showed that Ob-R expression was a significant determinant for HCC (odds ratio 0.02, 95% confidence interval 0.01 to 0.85; p = 0.041). Conclusion: Ob-R expression may have a potential role in the carcinogenesis of HCC. The positive association of Ob-R expression in the cancerous lesions of HCC with the survival outcome can be explained by its inverse correlation with vascular invasion, and may have prognostic value in HCC.

Head and neck extranodal lymphoma in a single institute: A 17-year retrospective analysis

The studys purposes are to identify patient characteristics, treatment response and survival rate, and to describe the important prognostic factors for our patients with extranodal head and neck lymphoma. Furthermore, no study has systemically discussed the overall figure of this disease in Taiwan and we analyzed our data on this topic. A retrospective review was performed for 86 patients with extranodal head and neck lymphoma, diagnosed in Kaohsiung Medical University Hospital, between 1990 and 2007. We evaluated the medical records and analyzed the possible factors affecting treatment outcomes, survival rate, and free‐from‐disease (FFD) survival rate. Forty‐nine male and 37 female patients were included with a male:female ratio of 1.32：1. The most frequent histologic type was diffuse large B cell lymphoma, accounting for 41.9% of the total. The most common primary site involved with extranodal head and neck non‐Hodgkins lymphoma was a tonsil with 27 cases (31.4%). Stage, international prognostic index (IPI) score, B symptoms, lactate dehydrogenase (LDH) level, and lymph node status significantly affected treatment response. The overall 5‐ and 10‐year survival rates were 68.0% and 57.8%, respectively. The FFD survival rate was 53.6% and 49.3% at 5 and 10 years, respectively. Factors including stage, lymph node status, LDH level, and IPI score produced significant differences in both overall survival and FFD survival. Our analyzed information is similar to other previously presented studies. Stage, IPI score, B symptoms, LDH level, and neck nodal status can be used to evaluate the treatment outcomes. Neck nodal status and stage are the two significant prognostic factors for overall survival.

Primary gastrointestinal follicular lymphoma: a clinicopathologic study of 13 cases from Taiwan.

Goals Follicular lymphoma (FL) is a common nodal lymphoma. Primary gastrointestinal follicular lymphoma (GIFL) is rare and most commonly occurs in the elder women with indolent clinical course, mainly in the duodenum and terminal ileum. We conducted this study to characterize GIFL in Taiwan. Study A total of 13 cases were retrospectively collected in 4 hospitals in southern and eastern Taiwan up to 2006. Pathology review and immunohistochemistry were performed and the clinical data were obtained from chart review. Results There were 5 men and 8 women with a median age of 58 years (range, 31 to 74; mean, 55). The most frequent site was ileum (7/13, 54%) with 4 tumors in the terminal ileum and the most common symptom was abdominal pain (8/13, 62%). Multiple lymphomatous polyposis was present in 6 patients (46%). Five (45%) of 11 tumors with surgical resection showed transmural involvement. Most of the cases revealed a predominantly follicular pattern (7/13, 54%) and low-grade disease (grades 1 and 2; 10/13, 77%). The tumors expressed CD10 (62%), Bcl-2 (77%), Bcl-6 (77%), and MUM1 (38%). Five patients (38%) were at stage IE and 8 (62%) at stage IIE. Treatment included surgery with or without chemotherapy. All patients achieved complete remission and relapse occurred in 3 patients. At a median follow-up time of 51 months (range, 3 to 180; mean, 63), 11 patients (85%) were disease free and no patient died of lymphoma. Conclusions We characterized the clinicopathologic features of the first series of GIFL in Taiwan. These tumors frequently involved ileum with a favorable prognosis.

Perforation predicts poor prognosis in patients with primary intestinal diffuse large B‐cell lymphoma

Aims: To elucidate the clinicopathological features and prognostic factors of primary intestinal diffuse large B‐cell lymphoma (PI‐DLBL).

Involvement of DNA Damage Response Pathways in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) has been known as one of the most lethal human malignancies, due to the difficulty of early detection, chemoresistance, and radioresistance, and is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. Its development has been closely associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Genetic alterations and genomic instability, probably resulted from unrepaired DNA lesions, are increasingly recognized as a common feature of human HCC. Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. It has been demonstrated that various HCC-associated risk factors are able to promote DNA damages, formation of DNA adducts, and chromosomal aberrations. Hence, alterations in the DDR pathways may accumulate these lesions to trigger hepatocarcinogenesis and also to facilitate advanced HCC progression. This review collects some of the most known information about the link between HCC-associated risk factors and DDR pathways in HCC. Hopefully, the review will remind the researchers and clinicians of further characterizing and validating the roles of these DDR pathways in HCC.

Cavernous Hemangioma of the Pancreas : Report of a Case

Nonepithelial tumors of the pancreas, including malignant lymphoma and benign and malignant soft tissue tumors, account for only 1–2% of all pancreatic tumors (1). Vascular tumors, classified as benign soft-tissue tumors, are even more uncommon; most have been reported in isolated cases. One-hundred

Increased caveolin-1 expression associated with prolonged overall survival rate in hepatocellular carcinoma.

Aims: Recent study indicates that the binding of caveolin‐1 (CAV1), the essential constituent of caveolae, to endothelial nitric oxide synthase (eNOS) prevents nitric oxide (NO) production in cirrhotic human liver. However, their interplay in hepatocellular carcinoma (HCC) remains undetermined. Methods: Paraffin‐embedded sections from 73 HCC patients were included in this study. The expression patterns of CAV1 and eNOS determined by immunohistochemistry were correlated with the clinicopathological characteristics and overall survival. Results: Although CAV1 expression did not correlate with any clinicopathological characteristic, increased CAV1 expression was associated with prolonged overall survival (p = 0.021), even when using the multivariate Coxs regression model (OR = 0.25, 95%CI = 0.08–0.72, p = 0.011). eNOS expression was correlated with an increased histological grade (p = 0.002) and intriguingly, the patients had a decreased overall survival when their lesions presented with high eNOS but low CAV1 expression concomitantly (p = 0.003). Meanwhile, the increased CAV1/eNOS merged level determined by immunofluorescence was significantly associated with a decreased histological grade and better overall survival (p = 0.023 and 0.001, respectively). Conclusions: Our results suggest CAV1 may play a tumour‐suppressive role and can serve as a predictive biomarker in HCC. The impacts of CAV1 on hepatocarcinogenesis may occur partly through its modulation of eNOS.

SOCS-3 is associated with vascular invasion and overall survival in hepatocellular carcinoma

Aims: Alteration of the suppressor of cytokine signalling‐3 (SOCS‐3) has been observed in certain human cancers. However, the clinical role of this short‐lived protein in hepatocellular carcinoma (HCC) is not well established. Therefore, we aimed to explore the potential role of SOCS‐3 proteins in HCC. Methods: Paraffin embedded sections from 87 HCC patients were included in this study. The expression patterns of SOCS‐3 proteins were analysed using immunohistochemistry and the results were correlated with clinicopathological characteristics and overall survival of the HCC patients. Results: The SOCS‐3 expression of HCC lesions and the adjacent non‐tumourous liver tissues was significantly correlated (p = 0.035), while the SOCS‐3 expression in HCC lesions was significantly and positively correlated with vascular invasion and histological grading (p = 0.034 and 0.032, respectively). The Kaplan–Meier survival curve showed that the HCC patients with high SOCS‐3 expression were associated with a poor overall survival rate in the HCC subgroup with positive vascular invasion (p = 0.014). Furthermore, a multivariate Cox regression model showed that SOCS‐3 expression was also a significant determinant of the overall survival for HCC (p = 0.006). Conclusions: Our results indicate that altered SOCS‐3 expression is associated with the overall survival in a subset of HCC patients with positive vascular invasion. Constitutive and altered SOCS‐3 expression may have potential roles in a subset of HCC patients.