Negative implication of C-MYC as an amplification target in esophageal cancer.

Chromosomal aberrations (amplifications and deletions) underlie the genesis or development of cancer. Amplification of 8q24 is one of the most frequent events in esophageal cancer. To define whether C-MYC is the target gene for 8q24 amplification, we performed fluorescence in situ hybridization using a MYC (8q24.12 approximately q24.13) probe in esophageal cancer from southern China. Furthermore, we detected the expression status of several genes including C-MYC, TRIB1 (alias C8FW), and FAM84B (alias NSE2) in the regions of 8q24 via reverse transcriptase-polymerase chain reaction or immunohistochemical analysis (or both). Distinct amplification of 8q24 was found in esophageal carcinomas. Only 4 of 46 cases showed obvious protein expression in part of the esophageal cancerous nest. In particular, increased protein expression of C-MYC was shown only in a small part of a cancerous nest in the four cases. Positive C-MYC staining was detected mainly in the cytoplasm of esophageal cancer cells. No expression of TRIB1 was detected in esophageal squamous cell carcinomas. Of 59 cases, 39 (66%) cases showed increased expression of FAM84B in esophageal carcinomas. The results suggest that C-MYC and TRIB1 may not be the amplification target of 8q24 in esophageal cancer. FAM84B might be involved in the genesis or development of esophageal cancer in southern China. Whether FAM84B is the amplification target of esophageal cancer awaits further investigation.

[Identification of stage Ib specific related genes in lung squamous cell cancer by oligonucleotide array].

OBJECTIVE: To establish gene expression profile of stage Ib and IIIa primary lung squamous cell cancer (SCC) within whole genome and identify genes specifically expressed in stage Ib of SCC. METHODS: Total RNA was extracted from the normal, stage Ib and IIIa lung SCC tissue. cRNA probes prepared from total RNA were hybridized with pretreatment oligonucleotide chip containing 22215 genes. The resultant data were treated with MSV 5.0 software and looked up on the affymetrix website. RT-PCR examination were used to validated the results from chip analysis. RESULTS: Comparing with the normal lung, difference genes expressed in Ib SCC are totally 1764, among which 571 were upregulated and 1193 were downregulated, and in stage IIIa, they are 554, 128 and 426 genes respectively. Genes specifically expressed in stage Ib were totally 1329, including 482 upregulation genes and 847 downregulation genes, which were classified into different category which included 480 metabolism related genes, 227 signal transduction genes, 136 cell proliferation genes, 136 immune related genes, 94 cell adhere genes, 88 transcription regulation genes, 86 cell cycle genes, 73 cytoskeleton genes, 45 differentiation genes, 42 apoptosis and 31 extracellular matrix genes. RT-PCR examination of FOXM1 and TNXB genes was consistent with the analysis of gene chip. CONCLUSION: Stage Ib and IIIa Gene expression profile of primary SCC within the whole genome were set up and genes specifically expressed in stage Ib of SCC were identified, which lay a foundation for further research on carcinogenesis mechanism and identifying new markers of early diagnosis.

Absence of evidence for HER2 amplification in nasopharyngeal carcinoma.

HER2 (c-erbB-2) has been suggested to be a prognostic factor in a variety of human cancers including breast, gastric and ovarian cancers. This study is therefore designed to identify changes of HER2 in nasopharyngeal carcinoma (NPC), an epithelia-derived malignancy with strong racial and geographic distribution. Interphase FISH and immunohistochemical (IHC) staining were used to analyze the gene copy number and protein expression of HER2 in 45 cases of NPC from Guangzhou, Southern China, an area with the highest incidence of NPC in the world. Our results, however, found no significant alterations in gene copy number for HER2, although IHC staining detected expression of HER2 oncoprotein in 33% of the 45 NPC tumors. No correlation was observed between HER2 expression and sex, age and clinical outcome of the patients, T stage, lymph node status, site and histopathological grading of the tumors. These results cast doubt on the value of HER2 as a prognostic factor for NPC.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma.

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to investigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological parameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene amplification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prognosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patients with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated significantly with tumor size and postoperative survival time of HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P=0.257), but not related to sex, age, AFP level, HBV infection, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was examined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 patients with aneuploidy (52.4%). No significant relations were observed between the HER-2 oncogene copy, patient sex, tumor size, histopathological grading, clinical staging, postoperative relapse and survival time (P>0.05); but the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P<0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromosome 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and progression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the recurrence and poor survival in patients with large HCC.

[Loss of p53 gene and amplification of HER-2 oncogene in primary hepatocellular carcinoma and their clinical significance].

OBJECTIVE: To investigate the deletion of p53 gene and amplification of HER-2 oncogene at chromosome 17 in primary hepatocellular carcinoma (HCC) and the clinical significance. METHODS: Interphase dual fluorescence in situ hybridization (FISH) was applied to detect the ratio of the number of p53 gene copy or HER-2 oncogene copy to that of chromosome 17 copy, to determine the p53 gene deletion and HER-2 oncogene amplification in nuclei prepared from 42 surgical specimens of HCC. Statistical analysis for their clinical significance was performed. RESULTS: Loss of p53 gene and amplification of HER-2 oncogene were detected in 27 (64.3%) and 9 (21.4%) of the 42 HCC respectively including 4 cases with low and 5 with high copy amplification. Six (14.3%) of 42 HCC showed simultaneously p53 gene deletion and HER-2 oncogene amplification. 61.9% (26/42) of HCC were polysomy 17, which correlated positively with p53 gene deletion (chi(2) = 12.286, P < 0.001). No close correlation between p53 gene loss and HER-2 oncogene amplification was found (chi(2) = 0.00, P = 1.00). Loss of p53 gene was related to the serum alpha-fetoprotein (AFP) level and the tumor size (P < 0.05). The postoperative 2-year survival rate (18.5%) of HCC patients with p53 gene deletion was significantly lower than postoperative 2-year survival rate (60.0%) of those without p53 gene loss (chi(2) = 7.467, P = 0.006). Meanwhile, HER-2 oncogene amplification showed a tendency of correlation with the tumor size (chi(2) = 2.973, P = 0.085), and the postoperative 2-year survival rate (0/9) of HCC patients with HER-2 oncogene amplification was significantly lower than those (42.4%) without HER-2 oncogene amplification (chi(2) = 3.977, P = 0.046). CONCLUSION: There were a high frequency of p53 gene deletion and a low frequency of HER-2 oncogene amplification in primary HCC, which might be involved in initiation and development of a subset of primary HCC.

[Chromosomal imbalance in primary lung squamous cell carcinoma and their relationship with smoking].

BACKGROUND & OBJECTIVE: Chromosomal imbalance plays an important role in tumorigenesis of lung cancer, and may be influenced by different carcinogens. This study was to examine chromosomal imbalance in primary lung squamous cell carcinoma (LSCC), and their association with smoking. METHODS: Chromosomal gains and losses in 39 specimens of LSCC were identified by comparative genomic hybridization (CGH), the association between chromosomal imbalances in LSCC and smoking was analyzed. RESULTS: The most frequent chromosomal gains of LSCC were detected on chromosomal arms 3q (74.4%, 29/39), 5p (66.7%, 26/39), 1q (43.6%, 17/39), 8q (41.0%, 16/39), 12p (42.6%, 18/39), 2p (38.5%, 15/39), and 18p (33.3%, 13/39), with minimal amplified regions (MAR) at 3q26.2-29 (74.4%, 29/39), 5p14.3-15.3 (66.7%, 26/39), 1q41-44(41.0%, 16/39), 8q23 (41.0%, 16/39), 12p13 (41.0%, 16/39), and 18p11.2 (33.3%, 13/39)u high-copy-number amplification at chromosomal arms 3q, and 5p were found in 15 (38.5%), and 6 (15.4%) patients. Chromosomal losses mainly involved chromosomal arms 3p (56.4%, 22/39), 5q (53.8%, 21/39), 13q (51.3%, 20/39), 8p (46.1%, 18/39), 4p (43.6%, 17/39), 4q (43.6%, 17/39), 1p (41.0%, 16/39), 2q (38.5%, 15/39), 9q (35.9%, 14/39), 13p (35.9%, 14/39), 16p (35.9%, 14/39) ,6p (33.3%, 13/39), and 6q (30.7%, 12/39), with minimal deleted regions (MDR) at 3p14.2-21.2 (51.3%, 20/39), 5q15-22 (51.3%, 20/39), 13q14.2-21.2 (48.7%, 19/39), 8p21.1-22 (43.6%, 17/39), 2q32 (35.9%, 14/39), and 16p12-13.1 (33.3%, 13/39). Amplification rates of chromosomal arms 3q, and 8q in smoking LSCC patients were significantly higher than those in non-smoking LSCC patients (P=0.002,P=0.031). While high incidences of gains at chromosomal arms 5p and 12p, and of losses at chromosomal arms 3p, 4q, and 5q were the common feature of chromosomal changes of smoking and non-smoking LSCC patients. CONCLUSION: 3q, 5p, 1q, 8q, 12p, 2p, 18p gains and 3p, 5q, 13q, 8p, 4p, 4q, 1p, 2q, 9q, 13p,16p, 6p, 6q loses might be involved in tumorigenesis and/or progression of LSCC, smoking-induced lung cancer may be associated with 3q, 8q gains.