Comparison between analysis of HER2 gene and chromosome 17 in breast cancer by dual-probe chromogenic in situ hybridization and fluorescence in situ hybridization / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the application of dual-probe chromogenic in situ hybridization (dual-probe CISH) in analysis of HER2 gene status of breast cancer patients by comparison with fluorescence in situ hybridization (FISH). The potential impact of chromosome 17 polysomy in the determination of HER2 status was also studied.</p><p><b>METHODS</b>One hundred and forty-six cases of paraffin-embedded breast cancer tissues were retrieved. Analysis of HER2 gene and chromosome 17 copy numbers using CE-approved commercial kits of dual-probe FISH (for 146 cases) and dual-probe CISH (for 73 cases) were carried out. The results were interpreted according to ASCO/CAP, 2007 either HER2 gene copy number or the ratio of HER2/centromere 17 (CEN17).</p><p><b>RESULTS</b>Of the 73 cases analyzed by both FISH and dual-probe CISH, the concordance rates for negative and positive results was 91.7% (33/36) and 97.4% (37/38) respectively, while the overall concordance rate between the two methods was 95.9% (70/73). Of the 146 cases analyzed by FISH, 13 cases were interpreted as equivocal if only HER2 copies were counted, compared with 8 equivocal cases by calculating the ratio of HER2/CEN 17. Moreover, 3 cases (4.8%) of the 63 HER2-positive cases determined by HER2 copies turned out to be HER2-negative when determined by the ratio of HER2/CEN 17; while using dual-probe CISH, 1 (3.0%) of the 33 positive cases turned out to be negative. In addition, when using FISH, there were more chromosome 17 polysomy cases (63.5%, 40/63) in the HER2-positive subgroup than HER2-negative subgroup (37.3%, 28/75) (P = 0.002).</p><p><b>CONCLUSIONS</b>Dual-probe CISH can achieve similar results as compared to FISH, indicating that this technology is a reliable alternative to FISH in HER2 testing. The accuracy can further be improved when HER2 and chromosome 17 are simultaneously tested and counted.</p>

Relationship between the protein expression of P53, c-erbB-2, vascular endothelial growth factor and CD44 and the survival rates of stage II( colorectal cancer patients without radiochemotherapy after radical resection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relation between protein expression of 4 genes [P53,c-erbB-2,vascular endothelial factors(VEGF) and CD44]and survival rate in stage II( colorectal cancer(CRC) patients without radiochemotherapy after radical resection.</p><p><b>METHODS</b>One hundred and fifty-nine cases of stage II(CRC without radiochemotherapy were enrolled in this study. The clinicopathological date and 5-year follow-up data were reviewed. Streptavidin-peroxidase immunohistochemical technique was used to detect the expression of P53, c-erbB-2, VEGF and CD44 in formalin-fixed, paraffin embedded sections of CRC tissues from above 159 patients.</p><p><b>RESULTS</b>The 5-year survival rate was 82.4%. The rates of positive expression of P53, c-erbB-2, VEGF and CD44 were 58.5%(93/159), 26.4%(42/159), 57.9%(92/159) and 40.0%(54/159) respectively. The 5-year survival rates of positive expression patients were not significantly different with those of negative expression. chi(2) analysis showed that the positive expressions of 4 genes had no relationships with the prognosis.</p><p><b>CONCLUSION</b>The expression of 4 gene proteins has no relationship with the prognosis of stage II( CRC patients without radiochemotherapy after radical resection.</p>

Multifocal papillary thyroid carcinoma: clinical analysis of 168 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and treatment of multifocal papillary thyroid carcinoma (PTC).</p><p><b>METHODS</b>A retrospective survey was carried out in 648 patients with PTC who underwent surgery from January 1997 to December 2006. One hundred and sixty-eight cases of the patients presented with multiple tumor masses (> or = 2). The risk factors, including sex of the patients, age at diagnosis, family history of thyroid tumor, multiplicity and bilaterality of tumor, extra-thyroidal extension, lymph node involvement and other were analyzed between solitary PTC and multifocal PTC group.</p><p><b>RESULTS</b>The mean age of the patients was 42 years (range, 14 - 78 years), included 49 male and 119 female. Tumor foci were found in both thyroid lobes in 117 cases (69.6%). Patients with multifocal PTC were characterized by a higher ratio of male (P = 0.004), family history of thyroid tumor (P = 0.031), neck lymph node metastasis (P = 0.008) and extra-thyroidal extension (P = 0.001). However, solitary PTC tended to be with a higher rate of benign goiters in pathologic examination. In multifocal PTC group, male, neck lymphadenectasis, > or = 3 tumor masses or bilaterality of tumor tended to presented with larger tumor, more neck lymph node metastasis and extra-thyroidal extension; And a less malignant tumor in the cases detected with benign goiters in histological examination. By the end of 2007, 164 cases (97.6%) completed follow-up with a mean period of 46.1 months (range, 2 - 127 months), 5 died in the meantime. One patient has been followed-up for 16 months for suspect of lung metastases by chest X-ray. Recurrence occurred in 8 patients and were re-resected, 2 in remnant thyroid and 6 in neck lymph nodes. The overall 1-, 2-, 5-, and 10-year survival rate was 98.2%, 97.4%, 96.5% and 96.5%, respectively. American Joint Committee on Cancer (AJCC) stage was associated with prognosis significantly (chi(2) = 168.832, P = 0.000).</p><p><b>CONCLUSIONS</b>Multifocus is one of the clinical features of PTC and is more malignant than solitary PTC. Total thyroidectomy with central compartment neck dissection could be standard treatment. Lateral nodal dissection is not necessary except for the cases with lymph node metastasis. AJCC stage is still the best prognostic factor.</p>

Estrogen receptor alpha variant ERalpha46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17beta-oestradiol / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors alpha and beta (ERalpha, ERbeta). The recently identified ERalpha46 resulted from exon 1-deletion from the 66-kDa full length form of ERalpha66 is devoid of the transactivation domain AF-1, whose function remains largely unknown.</p><p><b>METHODS</b>In this study, we compared the expression of ERalpha46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction (PCR). Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERalpha46, was transfected with ERalpha46-expression vector; methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17beta-oestradiol.</p><p><b>RESULTS</b>Higher ERalpha46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERalpha46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G(0/1) phase and a reduced proportion of cells in G(2)/M phase after exposed to 10(-8) mol/L 17beta-oestradiol. There were also more positive TUNEL stained cells in ERalpha46-transfected cells than the control cells in the presence of 17beta-oestradiol (P < 0.05).</p><p><b>CONCLUSIONS</b>These data suggest that ERalpha46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17beta-oestradiol.</p>

BRCA1/2 associated hereditary breast cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes, focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial; further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

Study on the prognostic value of hepatocyte growth factor and c-met for patients with hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the prognostic value of hepatocyte growth factor (HGF) and c-met for patients with hepatocellular carcinoma (HCC) after hepatectomy.</p><p><b>METHODS</b>Twenty-five patients undergoing partial hepatectomy for HCC were studied. Serum HGF level was determined using ELISA kit before and after operation respectively. c-met protein and mRNA expression in cancerous and paracancerous tissues were detected by immunohistochemical and RT-PCR methods respectively. The correlations of clinical-pathologic parameters with the HGF level in serum and c-met expression in cancerous tissue were analyzed respectively.</p><p><b>RESULTS</b>HCC patients had a significantly higher concentration of serum HGF than normal controls and chronic hepatitis B respectively [(1.03 +/- 0.09) ng/ml vs (0.69 +/- 0.02) ng/ml and (0.74 +/- 0.09) ng/ml]. No significant difference in serum HGF was observed between HCC and cirrhosis patients with Child-Pugh score B/C [(1.03 +/- 0.09) ng/ml vs (1.04 +/- 0.11) ng/ml]. Serum HGF concentrations were positively correlated with tumor size (> 5 cm), node cirrhosis, portal vein tumor thrombi (PVTT) and preoperative alpha-fetoprotein (AFP) level (> or = 400 microg/L). After the resection of tumor, serum HGF concentration had a peak on the third postoperative day (POD), and then declined, but did not return to normal level on the tenth POD. From preoperative day to third POD, HGF concentration had a higher elevation in patients with major resection than with local resection. Moderately or strongly positive expression of c-met protein was observed in 21 cancerous regions (21/25), and only in 5 paracancerous regions. The intensive expression of c-met mRNA was 100% (25/25) detectable in the cancerous tissues, but only 24% (6/25) in the paracancerous tissues. The expression extent of c-met protein was correlated with portal vein tumor thrombi (PVTT). In paracancerous tissues, the expression of c-met protein was more intense in patients with cirrhosis than those without cirrhosis. The patients with recurrence or metastases after operation had a higher level of serum HGF and more intensive expression of c-met than other patients. No significant association was observed between HGF in serum and c-met expression in cancerous tissue.</p><p><b>CONCLUSIONS</b>The over-expression of HGF and its receptor c-met indicate an adverse prognosis for HCC patients. The sustained high level of serum HGF after hepatectomy may be a factor related to early tumor recurrence and metastasis.</p>

Prognostic factors influencing postoperative survival in patients with

<p><b>OBJECTIVE</b>To summarize the experience of surgical resection, and to analyze the prognostic factors that can influence the postoperative survival in patients with small hepatocellular carcinoma (small HCC) of </= 3 cm in diameter.</p><p><b>METHODS</b>The clinicopathologic data of 105 cases with small HCC after resection between 1986 and 2003 were analyzed, all of which had been followed up for more than half a year (median time, 33 months). Nine clinicopathologic factors including preoperative alpha-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (> 2 cm vs. </= 2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method were analyzed through the way of Log-rank and Cox Regression tests.</p><p><b>RESULTS</b>Postoperatively, the cumulative survival rate of 1, 3 and 5-year were 86.5%, 70.3% and 55.2% respectively, and the disease-free survival rate of 1, 3 and 5-year were 78.0%, 58.9% and 45.6% respectively. One patient died from esophagogastric variceal hemorrhage in 2 weeks after re-operation. Up to the time of following up, 36 had intrahepatic recurrence or metastases postoperatively. Thirty-four patients died, of which, 4 died from variceal hemorrhage, 1 from liver failure, 1 died of pneumonia and 2 from distant metastases, while the others died from intrahepatic recurrences or metastases. Kaplan-Meier and multivariate Cox Regression tests indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. Multivariate Cox Regression tests indicated that tumor size, PVTT and multiple lesions were the factors affecting postoperative disease-free survival.</p><p><b>CONCLUSIONS</b>Limited hepatectomy with a margin no less than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are main factors leading to the death of patients with small HCC.</p>