The Prognostic Value of Pathological and Molecular Margins Marked by p53 and eIF4E in Laryngeal Carcinoma

Objective: To study the prognostic value of the pathological margin and molecular margin marked by eIF4E and P53 protein in laryngeal carcinoma. Methods: The prognostic value of pathological and molecular margin was studied in 253 cases and 67 cases respectively, the latter were pathological negative margin chosen from the former. Immunohistochemisty was used to detect the expression of eIF4E and p53 proteins. Results: The rate of pathological, p53 and eIF4E positive margins was 20.2%, 19.4% and 32.8% respectively. The recurrent rate of those with positive margins was higher than that of negative margins, which including pathological margin (70.6% vs 35.1%, P =0.0000), p53 margin (69.2% vs 33.3%, P =0.018) and eIF4E margin (63.6% vs 28.9%, P =0.018); The survival rate of those with negative margins was higher than those with positive margins, including pathological margin (the 5-year cumulative survival rate was 37.52% and 64.37% respectively, P =0.0023), p53 margin (the 5-year cumulative survival rate was 24.62% and 75.69% respectively, P =0.0012) and eIF4E margin (the 5-year cumulative survival rate was 43.31% and 77.52% respectively, P =0.0006). Conclusion: The prognosis of those with both pathological and molecular positive margins was worse than that of the negative margins; Both the eIF4E and p53 were useful markers to pick out the poor prognostic patients from those with pathological negative margin, and the former seemed to be more potential.

Liver transplantation for hepatocellular carcinoma： is zero recurrence theoretically possible？

BACKGROUND： Hepatocellular carcinoma（HCC） recurrence remains a key issue after liver transplantation. This study aimed to determine a subgroup of HCC patients within the Milan criteria who could achieve a theoretical goal of zero recurrence rates after liver transplantation.METHODS： Between 1999 and 2009, 179 patients who received liver transplantation for HCC within the Milan criteria were retrospectively included. Analysis of the factors associated with HCC recurrence was performed to determine the subgroup of patients at the lowest risk of recurrence.RESULTS： Seventy-two percent of the patients received a bridging therapy, including 54 liver resections. Eleven（6.1%） patients recurred within a delay of 19±22 months and ultimately died. Factors associated with recurrence were serum alpha-fetoprotein level 〉400 ng/m L, satellite nodules, poor differentiation, microvascular invasion and cholangiocarcinoma component. Recurrence rates decreased from 6.1% to 3.1% in patients without any of these factors.CONCLUSIONS： Among HCC patients within the Milan criteria, selecting patients with factors based on histology would allow tending towards zero recurrence, and prior histological assessment by liver biopsy or resection may be essential to rule out poorly differentiated tumors, microvascular invasion,and cholangiocarcinoma component.

Clinical use of hepatic carcinoma associated membrane protein antigen (HAg18-1) as reagent of enzyme linked immunosorbent assay for detection of primary hepatocellular carcinoma

AIMS To evaluate the sensitivity,specificity and clinical value of hepatic carcinoma associated mem- brane protein antigen (HAg18-1) used as a reagent of serum quick enzyme linked immunosorbent assay (ELISA) for the detection of primary hepatocellular car- cinoma (PHCC). METHODS Serum quick enzyme linked immunosor- bent assay (ELISA) with HAg18-1 as reagent,which was prepared by monoclonal antibody against human hepatic carcinoma,was performed on 100 cases of pri- mary hepatocellular carcinoma (PHCC),5 cases of hepatic biliary carcinoma (HBC),10 cases of metastatic hepatic carcinoma (MHC),20 cases of hep- atitis B (HB),20 cases of liver cirrhosis (LC),20 cas- es of gastrointestinal malignant tumours and 20 cases of gastronintestinal inflammatory diseases (including ulcers). Alpha-fetoprotein (AFP) detection concurrent- ly for each case. Twenty samples of bank blood were tested as controls. RESULTS Positive rate of HAg18-1 ELISA and AFP detection were 81% and 68% in PHCC,20% and 40% in HBC,19% and 20% in MHC,10% and 20% in BH, 10% and 20% in LC,10% and 15% in gastrointestinal malignant tumors,and 5% and 10% in gastrointestinal inflammatory diseases. No positive result of HAg18-1 ELISA and AFP detection occurred in any sample of bank blood. CONCLUSIONS HAg18-1 ELISA has high sensitivity and specificity in the detection of PHCC. HAg18-1 ELISA and AFP detection,if used together,may be complementary to each other in the diagnosis of PHCC.

Expression of β-catenin in renal cell carcinoma

Objective To investigate the expression of β-catenin and its mRNA in renal cell carcinoma.Methods Twenty-six cases with renal cell carcinoma (RCC) were studied by immunohistochemistry, Western blot and RT-PCR.Results We found the expression of β-catenis is higher in cancer tissues than in normal kidney tissues and the level of β-catenin is associated with the tumor stage. Its expression in tumor of pT3 and pT4 is obviously higher than pT1 and pT2 (P<0.01). That is to say, there was an overexpression of β-catenin protein in RCC and its level was related to the tumor stage, but the expression of β-catenin mRNA had no difference between tumor tissue and normal tissue.Conclusion β-catenin may be related to the occurrence and progress of RCC.

Suppression subtractive hybridization for identifying differentially expressed genes in renal cell carcinoma

Objective To construct a renal cell carcinoma (RCC) cDNA subtractive library using suppression subtractive hybridization.Methods Polyadenylated RNA ［Poly (A)+ RNA］ was isolated from tissues of RCC and normal kidney, and single-strand cDNAs and double-strand cDNAs were synthesized in turn. RCC cDNAs were divided into two groups and ligated to the specific adaptors l and 2, and then hybridized with normal kidney cDNA twice with two rounds of suppression PCR. Second round PCR products were cloned to T/A plasmid vectors to set up the subtractive library. One hundred clones were randomly picked to perform enzyme digest analysis, and some underwent sequence analysis and Northern blot to identify RCC specifically expressed genes. SMART RACE procedure was operated to clone full length novel RCC specifically expressed genes.Results A human RCC subtractive library with high subtractive efficiency was successfully set up. The amplified library contains 350 positive clones. Random analysis of 100 clones with enzyme restriction showed that 85 plasmids in the clones contained 50-400?bp inserts. Sequence analysis was performed for 10 clones. All the 10 sequences were unknown before and derived from 6 unique, novel genes among which the cDNA insert RCC18 had five copies. Northern blot analysis showed that RCC18 cDNA was highly expressed in RCC, but no signal could be detected in normal kidney. Using SMART RACE technique, we obtained the full length of the novel gene RCC18.Conclusions The constructed cDNA subtractive library of human RCC is a highly efficient one and lays a solid foundation for large scale screening and cloning new and specific oncogenes or tumor suppressor genes of RCC. The novel specifically expressed genes provided an important clue for studying the mechanisms of occurrence and development of RCC.

Detailed deletion mapping of loss of heterozygosity on 9p13-23 in laryngeal squamous cell carcinoma by microsatellite analysis

Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters Methods Tumor tissues were obtained from paraffin embedded sections with microdissection Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23 The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx KH*2/5DResults Of the 42 laryngeal cancers, 41 (97 6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23 The most frequently deleted marker was D9S162 in 17 of the 19 (89 5%) informative samples The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80 0%) LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50 0%) Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23 Multiple LOH (≥4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis ( P <0 01 or 0 01, 0 05, respectively) On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx Conclusions These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal SCC Multiple genetic alterations are probably implicated in supraglottic SCC with cervical lymph node metastasis in younger patients

Iressa治疗头颈部鳞状细胞癌

头颈部鳞状细胞癌由于解剖结构的限制，导致局部区域晚期、复发或转移的患者存在治疗上的困境，需要积极探索新的治疗方式。近年来以表皮生长因子受体为靶点的药物Iressa治疗头颈部鳞状细胞癌的研究不断增多，本文对此进行综述。