An analysis of HER-2/neu gene status in invasive ductal carcinomas using immunohistochemistry and fluorescence in situ hybridization
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Abstract:
To determine the concordance rates between results from immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays for the HER-2/neu gene in cases of invasive ductal carcinoma. IHC and FISH are 2 of the most frequently used methods to determine HER-2/neu gene status in invasive breast carcinomas. Materials and methods: The present study includes 59 female patients with invasive ductal carcinoma. The mean age was 57.8 years. Axillary lymph node status could be evaluated in 30 patients with axillary dissection. HER-2/neu gene overexpression and amplification were analyzed in primary tumor tissues by IHC and FISH assays, respectively. The evaluation of the IHC assay was performed using a score of 0, 1+, 2+, or 3+, while a HER-2/neu-to-CEP17 ratio greater than 2 was accepted as positive for HER-2/neu gene amplification. Results: The overall rate of HER-2/neu gene amplification was 28.8% (17 cases) among all members of the study group, while this rate was 48% (12 cases) in the group with axillary lymph node metastasis. The rate of HER-2/neu overexpression (score of 3+) was 11.9% (7 cases). HER-2/neu gene amplification was associated with tumor grade (P < 0.05). There was a significant relationship between the results of the IHC and FISH assays (P < 0.001). All of the cases with a score of 3+ were FISH-positive, while 97% of cases with a score of 0 and 44% of cases with a score of 1+ were FISH-negative. HER-2/neu gene amplification was determined in 80% of the cases with a score of 2+. Among cases with positive lymph node status, the concordance rates were 100% in cases with scores of 0, 2+, and 3+, while this rate was found to be 29% in cases with a score of 1+. Conclusion: Our found rate (11.9%) of HER-2/neu overexpression was lower than the rates reported in the literature, while our HER-2/neu gene amplification rate (28.8%) was compatible with the reported rates. HER-2/neu gene amplification was associated with tumor grade. Although high rates of concordance between HER-2/neu gene overexpression and amplification in cases with scores of 2+ and 3+ were obtained, the discordance rate in cases with a score of 1+ was higher than those of other studies. The discordance rate in cases with a score of 1+ and positive lymph node status was higher than that of the total study group. According to our results, a score of 1+ indicated less conclusive immunostaining for the HER-2/neu gene, and cases with scores of 1+ in the metastatic group had a higher rate of HER-2/neu gene amplification than that of the total study group. Our results show that FISH analysis for HER-2/neu gene status should be performed in cases with an immunostaining score of 1+, especially in those cases with positive axillary lymph node results.Keywords:
Concordance
Breast carcinoma
HER2/neu
Objective To study the routine methods that can be easily used in clinics to detect the Charcot Marie Tooth (CMT) disease gene duplication. Method Polymerase chain reaction(PCR) combined with restriction enzyme digestion and amplification of short tandem repeat (STR) sequence were used to detect gene duplication on chromosome 17p11.2～12 in 30 CMT1 patients and 10 CMT2 patients coming from unrelated families. 40 controls were also detected. Results 46.7%(14/30) of CMT1 patients were identified to have specific junction fragments. 53.3%(16/30)of them were identified as duplication by STR analysis. 70.0%(21/30) of CMT1 patients were identified to have gene duplication using both methods. Duplication was not identified in 10 unrelated CMT2 patients and 40 controls. Conclusion The PCR combined with restriction enzyme digestion represented a relatively sensitive and accurate method for detecting gene duplication in CMT1A cases for clinical diagnosis. The detecting rate of duplication can be increased using both restriction enzyme digestion of PCR products and STR methods.
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Aspergillus nidulans
Chromosome instability
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HER2/neu
Adeno-associated virus
Oral immunotherapy
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We present a 16-month-old boy with developmental delay, minor anomalies, small penis, and lymphedema of the upper limbs. Routine cytogenetic analysis suspected a duplication of 5q. Fluorescent in situ hybridization (FISH) with a cosmid probe (MCC at the 5q22 APC region) showed tandemly duplicated fluorescent signals on one of chromosomes 5, whereas FISH with three YAC probes (TYAC12 at 5q35, HTY3182 at 5q34, and TYAC139 at 5q31) did not give duplicated signals. These findings indicate a duplication of 5q22 band in one chromosome 5. The boy we describe here is the first case of a pure partial duplication of 5q to be proven by FISH techniques. A review of previously reported cases of putative partial 5q duplication showed no consistent phenotype. Am. J. Med. Genet. 83:361–364, 1999. © 1999 Wiley-Liss, Inc.
Cosmid
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Abstract BACKGROUND HER‐2/ neu is a valuable prognostic marker in primary breast carcinoma. Controversy surrounds the correlation between HER‐2/ neu expression and other prognostic markers, as has been discussed in preclinical and clinical studies. The objective of the current study was to investigate the probability, calculated using parameters that are assessed routinely in clinical practice, that patients with breast carcinoma had positive HER‐2/ neu status. METHODS The authors evaluated HER‐2/ neu status in 923 consecutive patients with breast carcinoma by immunohistochemical methods. Correlations involving HER‐2/ neu status, estrogen receptor (ER) and progesterone receptor (PR) status, tumor grade, patient age, lymph node involvement, and tumor size were evaluated using the Mantel–Haenszel chi‐square test and the Spearman correlation. The authors created a simple scoring system (i.e., the diagnostic instrument for validation of HER‐2/ neu score) to define subgroups of patients with breast carcinoma and to determine the likelihood of HER‐2/ neu positivity. RESULTS HER‐2/ neu overexpression was correlated significantly with negative ER ( P = 0.0001) and PR status ( P = 0.0001), Grade 3 (G3) lesions ( P = 0.0001), and young age ( P = 0.006). The likelihood of HER‐2/ neu positivity in a patient with positive ER and PR status and G1/G2 disease was approximately 6.1%. CONCLUSIONS The authors demonstrated in a large patient series that HER‐2/ neu overexpression was associated with negative hormone receptor status, G3, and young age. In a subgroup of patients presenting with hormone‐responsive and G1/G2 tumors, the likelihood of HER‐2/ neu overexpression was very small. Therefore, the assessment of HER‐2/ neu status in this subgroup of patients with breast carcinoma may be considered unnecessary, unless the role of HER‐2/ neu status in adjuvant treatment has been proven. Cancer 2003;98:2547–53. © 2003 American Cancer Society.
Breast carcinoma
HER2/neu
Progesterone receptor
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Abstract Duplication of all genes associated with X‐linked intellectual disability (XLID) have been reported but the majority of the duplications include more than one XLID gene. It is exceptional for whole XLID gene duplications to cause the same phenotype as sequence variants or deletions of the same gene. Duplication of PLP1 , the gene associated with Pelizaeus‐Merzbacher syndrome, is the most notable duplication of this type. More commonly, duplication of XLID genes results in very different phenotypes than sequence alterations or deletions. Duplication of MECP2 is widely recognized as a duplication of this type, but a number of others exist. The phenotypes associated with gene duplications are often milder than those caused by deletions and sequence variants. Among some duplications that are clinically significant, marked skewing of X‐inactivation in female carriers has been observed. This report describes the phenotypic consequences of duplication of 22 individual XLID genes, of which 10 are described for the first time.
Segmental duplication
Sequence (biology)
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ABSTRACT Salmonella typhimurium strains containing a duplication of nearly a third of the genome have been isolated by a simple procedure involving selection for improved utilization of L-malate as sole carbon source. The duplication occurs at a very high spontaneous frequency. Strains containing the duplication can be isolated selectively on malate medium, or by a non-selective procedure involving Hfr conjugation. When strains containing the duplication are maintained on non-selective medium, the duplication is readily lost. Genetic evidence suggests that the duplication is chromosomal and tandem. The fact that the recA gene is included in the duplication has been used to obtain evidence that the recA1 marker is recessive to its wild-type allele. Unlike tandem duplications previously described in E. coli, the duplication described in this report appears to have unique endpoints
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HER2/neu
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The C4 gene duplication has been studied among 78 families with 366 members in Chinese.
This study allowed the detection of 7 groups of C4 gene duplication or triplication in the family
material rlpresenting an overall frequency of 9.0%.The total members with duplicated of tripli-
cated C4 genes were 17,which representsa frequency of 6.4%.The duplicated C4 gnes all be-
long to the C4B genes.The kinds of C4B gene duplication and the number each are:①)C4B(1,
2)×2,②B(1,12)×6,③B(1,1)×5,④B(1,96,96)×2 and ⑤B(2,2)×2.
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Duplication is thought to be one of the main processes providing a substrate on which the effects of evolution are visible. The mechanisms underlying this chromosomal rearrangement were investigated here in the yeast Saccharomyces cerevisiae. Spontaneous revertants containing a duplication event were selected and analyzed. In addition to the single gene duplication described in a previous study, we demonstrated here that direct tandem duplicated regions ranging from 5 to 90 kb in size can also occur spontaneously. To further investigate the mechanisms in the duplication events, we examined whether homologous recombination contributes to these processes. The results obtained show that the mechanisms involved in segmental duplication are RAD52-independent, contrary to those involved in single gene duplication. Moreover, this study shows that the duplication of a given gene can occur in S.cerevisiae haploid strains via at least two ways: single gene or segmental duplication.
RAD52
Gene conversion
Gene dosage
Segmental duplication
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