The Relationship between 67KD Laminin Receptor Expression and Metastasis of Hepatocellular Carcinoma

The 67KD laminin receptor (LN-R ) that binds laminin (LN) is involved in the metastasis cascade. Using immunohistochemical technique, in situ hybridization and reverse transcription polymerase chain reaction(RT-PCR), we studied LN-R protein and RNA levels in 30 cases of human hepatocellular carcinoma (HCC) to further understand its role in the metastasis of HCC. In our 14 cases of HCC with metastasis, its positive rates were 71. 4 %, 57. 1%, 85.7% respectively, whereas its positive expression in 16 cases without metastasis were 31.3 %, 18. 8 %, 50. 0 % respectively. The significant difference was found between these two groups. The results suggest that the 67KD LN-R expression plays a very important role in the metastasis of HCC.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma

AIM: To investigate and evaluate the change in healthrelated quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM StageⅠto Stage Ⅱ, Stage ⅢA, Stage ⅢB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage Ⅰ to Stage ⅢB (P = 0.002 vs Stage Ⅰ; P = 0.032 vs Stage Ⅱ; P = 0.033 vs Stage ⅢA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage Ⅱ; P = 0.032 vs Stage ⅢA). For the social and family well-being subscale, only Stage ⅢB scores were significantly lower as compared with Stage Ⅰ scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages ⅡΙ, ⅢA and ⅢB (P = 0.002vs StageⅠ). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.

Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma

AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.

Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.

Cycle number of neoadjuvant chemotherapy might influence survival of patients with T1-4N2-3M0 nasopharyngeal carcinoma

Objective： Stage N2-3 nasopharyngeal carcinoma（NPC） shows a high risk of distant metastasis, which will finally cause death. This study aimed to evaluate the impact of neoadjuvant chemotherapy（NACT） of various cycles before radical radiotherapy on distant metastasis and survival of patients with stage N2-3 diseases.Methods： In this study, a total of 1,164 consecutive patients with non-metastatic N2-3 NPC were recruited and prospectively observed. Then 231 patients who received NACT of 4 cycles（NACT=4 group） were matched 1：2：1 to 462 patients treated with NACT of 2 cycles（NACT=2 group） and 231 patients treated without NACT（NACT=0 group）, according to age, histological subtype, N stage and NACT regimen. Five candidate variables（sex, T stage, concurrent chemotherapy, intensity-modulated radiation therapy and cycle number of NACT） were analyzed for their association with patients＇ survival.Results： After matching, the overall survival（OS）, disease-free survival（DFS）, local-recurrence-free survival（RFS） and distant-metastasis-free survival（MFS） of the NACT=4 group（89.2%, 81.0%, 83.3% and 84.8%,respectively） were better than those of the NACT=2 group（83.3%, 72.5%, 81.2% and 77.9%, respectively） and the NACT=0 group（74.0%, 63.2%, 74.0% and 68.8%, respectively）. In multivariate analysis, the cycle number of NACT maintained statistical significance on the OS, DFS, RFS and MFS（all P〈0.05）.Conclusions： For N2-3 NPC, cycle number of NACT appeared to be an independent factor associated with an improvement of survival.

EXPRESSIONS OF ESTROGEN OCCUPIED RECEPTOR(EoR)AND PROGESTERONE OCCUPIED RECEPTOR(PoR)AND C-erbB-2 ONCOPROTEIN IN HUMAN NASOPHARYNGEAL CARCINOMAS

It is first reported here that estrogen occupied receptor(EoR)and progesterone occupied receptor (RoR)expressed in cancerous tissues (59.57% and 82.98% respectively)and morphologically normal epithlium(50 77.78% and 70-88.89%respectively) in nasoplharyngeal carcinomas(NPCs)with insignificant difference(P>0.05).Positive rates of EoR and PoR increased greatly in clinical stage Ⅲ and Ⅳ, compared with in Ⅱ(P<0.05), and exhibited insignificant difference between female cases and male ones(P>0.05).Positive rate of C-erbB-2 was 19.15% in cancerous cells, and 9.68% in stage Ⅲand 66.67% in Ⅳin NPCs(P<0.05).Significant difference of C-erbB-2expression was observed between bilateral cervical lymph node metastasis(BCLM)and unilateral ones(P<0.05)but not for EoR or PoR(P>0.05)These findings suggest that EoR or PoR may be correlated with aggravation but not genesis and node metastasis in NPCs and that C-erbB-2may be correlated with aggravation and promotion of formation of node metastasis in NPCs.

Correlation between Central and Lateral Neck Dissection in Differentiated Thyroid Carcinoma

Objective: To determine the histopathological correlation between central and lateral neck metastasis in differentiated thyroid carcinoma, and its potential therapeutic impact. Although the central neck dissection (CND) is recommended in differentiated thyroid carcinoma, the indication for lateral neck dissection (LND) remains controversial. Design: Retrospective study. Methods and Main Outcome Measures: Pathological analysis of systematic ipsilateral central neck dissection (CND) and LND performed with total thyroidectomy in differentiated thyroid carcinoma was retrospectively reviewed according to “side” and to “patient”. Results: A total of 56 sides (46 patients) were suitable for analysis. Analysis by “side” revealed that CND and LND dissection samples were both negative in 15 cases, both positive in 32, CND was positive and LND was negative for 8 cases and CND was negative and LND was positive in 1 case. The combined presence of positive LND and positive CND was therefore observed in 32/40 “sides” and 26/46 “patients”. Analysis by “side” of the impact of the treatment decision to perform ipsilateral LND only in patients with positive CND and vice versa demonstrated a sensitivity, specificity, and accuracy of 97%, 65%, and 84%, respectively. Conclusions: In most cases, the presence of positive LND was associated with positive ipsilateral CND. The very low prevalence of positive LND in patients with negative CND may justify LND as a second step procedure only in patients with positive CND, except in the case of documented lateral neck metastasis.

Pathological clavicular fracture as first presentation of renal cell carcinoma: a case report and literature review

Renal cell carcinoma(RCC) accounts for approximately 3% of all cancer cases. RCCs usually metastasize to the lungs, bones, liver, or brain. Only <1% of patients with bone metastases manifested clavicular RCC metastases. Thus, clavicular metastasis as the initial presentation of RCC is extremely rare. We report a patient with RCC metastasis to the left clavicle, which was first presented with pain caused by a pathological fracture. Magnetic resonance image revealed a renal tumor, and technetium-99m–methylene diphosphonate bone scintigraphy showed multiple osseous metastases. The patient eventually underwent surgery to remove the lateral end of the left clavicle and right kidney. Histopathology revealed renal tumor and clear cell carcinoma in the clavicle. Finally, we review 17 cases of clavicular metastases originating from different malignancies.

HLA-A*02-B*46 Haplotype: an Adverse Prognostic Factor in Han Patients with Nasopharyngeal Carcinoma

Epidemiological studies have shown that human leukocyte antigen（HLA） allelic polymorphisms are closely correlated to susceptibility to nasopharyngeal carcinoma（NPC）, and in a previous study, we showed that HLA-B＊46 and HLA-A＊02-B＊46 haplotypes were strongly associated with NPC susceptibility. In this retrospective study, we investigated the phenotype of the HLA-A and HLA-B alleles and haplotypes and correlated these data to the clinical and pathological parameters of NPC to understand the role of HLA alleles and haplotypes in NPC prognosis. The cohort comprised 117 NPC patients from a Han population in Xinjiang. The local recurrence-free survival（LRFS）, distant metastasis-free survival（DMFS）, disease-free survival（DFS）, and overall survival（OS） were analyzed. The 5-year DMFS of the HLA-A＊02-B＊46 haplotype carriers and non-carriers was 66.4% and 90.3%, respectively. In addition, age was found to be a prognostic factor for LRFS, DFS, and OS（P=0.032, 0.040, and 0.013, respectively）. We found that the HLA-A＊02-B＊46 haplotype might be a prognostic marker in addition to the traditional TNM staging in patients with NPC.

Positive association of RhoC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma

Worldwide estimates establish gastric carcinoma as the second most frequent cause of cancer deaths. Tumour invasion and metastasis is the biggest impediment to gastric carcinoma cure. Active migration of tumour cells is now considered as the pivotal step in cancer invasion and metastasis. RhoC is a member of the Ras-superfamily of small guanosine triphosphatases that can regulate many cellular functions, especially cytoskeletal organization and cell locomotion. Overexpressing RhoC in vitro in the poorly metastatic cell line from human melanoma may induce a highly metastatic phenotype.~1 The recent development of laser capture microdissection (LCM) affords the opportunity to further evaluate the role RhoC plays in the invasion and metastasis of gastric carcinoma cells in their native tissue environment.

Role of surgical resection for non-colorectal non-neuroendocrine liver metastases

It is widely accepted that the indications for hepatectomy in colorectal cancer liver metastases and liver metastases of neuro-endocrine tumors result in relatively better prognoses, whereas, the indications and prognoses of hepatectomy for non-colorectal non-neuroendocrine liver metastases(NCNNLM) remain controversial owing to the limited number of cases and the heterogeneity of the primary diseases. There have been many publications on NCNNLM; however, its background heterogeneity makes it difficult to reach a specific conclusion. This heterogeneous disease group should be discussed in the order from its general to specific aspect. The present review paper describes the general prognosis and risk factors associated with NCNNLM while specifically focusing on the liver metastases of each primary disease. A multidisciplinary approach that takes into consideration appropriate timing for hepatectomy combined with chemotherapy may prolong survival and/or contribute to the improvement of the quality of life while giving respite from systemic chemotherapy.

Sentinel lymph node detection by combined dye-isotope technique and its predictive value for cervical lymph node metastasis in patients with lingual carcinoma

Objectives To investigate the clinical value of combined dye-isotope technique in detecting sentinel lymph node (SLN) and to examine whether the characteristics of SLN accurately predict cervical lymph node metastasis in lingual carcinoma. Methods Thirty patients with lingual carcinoma without lymph metastasis were injected with a dose of about 18.5 MBq of 99m Tc-SC (sulfur colloid), around the tumor tissues before surgery,and lymphoscintigraphy was performed 5,10,30,60 minutes,and 6 hours after injection. In the following day,all patients were injected with isosulfan blue dye around the primary tumor during surgery to trace SLN and underwent standard cervical lymph node dissection after SLN dissection. The pathological results of SLN were compared with standard lymph node dissection for their ability to accurately predict the final pathological status of the cervical lymph nodes.Results SLN was successfully identified in 100% of the patients. Both positive and negative predictive values of SLN were 100%. The accuracy rate was 100%,and there were no false negatives. Conclusions The detection of SLN using combined dye-isotope technique could accurately predict cervical lymph node metastasis in lingual carcinoma.

Foxp3 Expression in CD4＋CD25＋Foxp3＋ Regulatory T Cells Promotes Development of Colorectal Cancer by Inhibiting Tumor Immunity

The mechanism underlying CD4~＋CD25~＋Foxp3~＋ regulatory T cells（Tregs） promoting the development of colorectal cancer（CRC） was elucidated in the present study. Forty-eight cases of colorectal carcinomas, 22 cases of colon polyps and 21 cases of normal colorectal tissues were collected. The correlation among Foxp3, IL-10 and Stat3, and the clinical relevance of these three indexes were analyzed. The results showed that the levels of Foxp3 expressed in infiltrating CD4~＋CD25~＋Foxp3~＋Tregs, and IL-10 and Stat3 in CRC tissues were all significantly higher than those in polypus tissues and normal colon tissues（P〈0.01）. Pearson correlation analysis indicated that the expression level of Foxp3 was positively correlated with Stat3 at m RNA level（r=0.526, P=0.036）, and was positively correlated with IL-10 at protein level（r=0.314, P=0.030）. The Foxp3 expressed in CD4~＋CD25~＋Foxp3~＋Tregs was correlated with the histological grade, lymph node metastasis and TNM stage of CRC（P〈0.05 for all）. The IL-10 expression was correlated with the histological grade and TNM stage（both P〈0.05）. The Stat3 expression was correlated with the lymph node metastasis and TNM stage（both P〈0.05）. It was concluded that CD4~＋CD25~＋Foxp3~＋Tregs can inhibit tumor immunity in combination with some other related inhibitory cytokines and that Foxp3 expression in CD4~＋CD25~＋Foxp3~＋Tregs correlates with CRC progression.

Expression and Clinical Significance of CD44vin Hum an Gastric Cancers

Expression of CD44v mRNA in 20 patients with gastric tumor was investigated to identify the correlation of the CD44 gene splice and abnormal expression with the clinicopathological changes. The results showed that CD44v mRNA was expressed in 16 of 20 gastric cancers. In 5 out of the 10 mucosa tissues adjacent to gastric cancer, However, no expression of CD44v mRNA was found in all 10 normal mucosa specimens; Positive expression was found in 15 of 16 patients with lymph node metastasis, and 1 out of 4 patients without lymph node metastasis, as well as 5 cases with distant metastasis (P<0.05). Positive expression of CD44v was found in 2 out of 5 well differentiated type gastric cancers, and 14 out of 15 poorly differentiated gastric cancers. Differences were found in the expression between the two types of gastric mucosa (P<0.05). All the mucosa samples including normal gastric mucosa, gastric cancer and its adjacent tissues presented the standard CD44v mRNA. The conclusion was that the abnormal expression of CD44v is a universal significance in gastric cancer, which might serve as an early marker of gastric cancer and metastasis.

THE SIGNIFICANCE OF IMMUNO-STAIN WITH HLC_3-AB IN CEREBRAL METASTATIC TUMOR

By using the immunohistochemical technique(ABCmethod), 186 cases of cerebral metastatic tumors labeled with McAb against human lung carcinoma are reported. They were divided into two groups: primary site determined group and undetermined group. In determined group(59 cases) . 33/36 cases( 91. 6 % ) of lung carcinomas showed HLC3 positive reactions, but among 23 cases of other cancers, only two cases showed weak positive reactions.This result indicated that the HLC3 have strong specific reaction to the lung carcinomas. In undetermined group( 127 cases), 68 cases of metastatic tumors reacted to HLC3 positively. In all 186 cases of cerebral metastatic tumor, there were 101 cases( 53. 5%) showing positive reaction to HLC3- AB. Among 125 cases of cerebral metastatic adenocarcinoma, 76 cases( 61 %) showed positive reactions with HLC3-AB. The result in this paper proved that the lung carcinoma was the important primary site of the cerebral metastatic tumor operated neurosurggically. The specifity of McAb HLC3- AB, the incidance of the cerebral metastatic lung carcinoma and its metastatic course were discaussed.

Metachronous contralateral testicular and bilateral adrenal metastasis of chromophobe renal cell carcinoma:a case report and review of the literature

Chromophobe renal cell carcinoma(ChRCC) metastatic to the testis has not,to the best of our knowledge,been reported in the literature.Nor have there been reports of delayed bilateral adrenal metastasis of ChRCC.Here we report a case of metachronous contralateral testicular and bilateral adrenal metastasis of ChRCC in a 70-year-old man who underwent right radical nephrectomy for RCC six years ago.He was admitted to the hospital because of left intrascrotal enlargement of two-month duration.Ultrasonography revealed a mass in the upper pole of the left testis.Computed tomography(CT) showed irregular masses in the bilateral adrenal area.Left radical orchiectomy and laparoscopic bilateral adrenalectomy were performed.The pathologic examination showed metastatic ChRCC in the left testis and bilateral adrenal gland.Postoperative follow-up showed that the patient had survived for at least 56 months without recurrence.The case highlights the unique behavior of RCC with an unusual site of metastasis and favorable survival after multiple metastasectomy.

Risk analysis of lymph node metastasis in 285 patients with superficial esophageal squamous cell carcinoma

Objective To identify risk factors of lymph node metastasis in superficial esophageal squamous cell carcinoma(ESCC),and to provide evidence for treatment choice under endoscope.Methods From January 2007 to December 2011,285 patients with pathologically diagnosed ESCC who received surgery and had clear record of lymph nodes resection were enrolled.The clinical pathological data of these patients were analyzed。