HER2 Status and Its Heterogeneity in Gastric Carcinoma of Vietnamese Patient

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is related to the pathogenesis and poor outcome of numerous types of carcinomas, including gastric carcinoma. Gastric cancer patients with HER2 positivity have become potential candidates for targeted therapy with trastuzumab. METHODS: We investigated 208 gastric cancer specimens using immunohistochemistry (IHC), fluorescence in situ hybridization and dual in situ hybridization (ISH). We also investigated the concordance between IHC and ISH. The correlation between HER2 status and various clinicopathological findings was also investigated. RESULTS: In total, 15.9% (33/208) and 24.5% (51/208) of gastric cancers showed HER2 gene amplification and protein overexpression, respectively. A high level of concordance between ISH and IHC analyses (91.3%, κ = 0.76) was found. A significant correlation between HER2 status and intestinal-type (p < .05) and differentiated carcinomas (p < .05) was also noted. The HER2 heterogeneity was high in gastric cancers; we found 68.8% phenotypic heterogeneity and 57.6% genotypic heterogeneity. Heterogeneity in HER2 protein expression and gene amplification showed a close association with diffuse histologic type and IHC 2+. CONCLUSIONS: HER2 protein overexpression and gene amplification were detected in 24.5% and 15.9% of gastric cancer specimens, respectively. Intestinal-type showed a higher level of HER2 protein overexpression and gene amplification than diffuse type. HER2 status also showed a significant relationship with well- and moderately-differentiated carcinomas. The ratio of phenotypic and genotypic heterogeneity of HER2 was high in gastric carcinomas and was associated with HER2 IHC 2+ and diffuse histologic type.

Chromosome 7 aneuploidy in clear cell and papillary renal cell carcinoma: Detection using silver in situ hybridization technique.

Background: Chromosome 7 aberrations in renal cell carcinoma (RCC) have been reported in papillary renal cell carcinoma (pRCC) and clear cell renal cell carcinoma (ccRCC). However, the implication of these anomalies on prognosis and survival is still unclear. RCC Chromosome 7 aberrations have commonly been detected by fl uorescent in situ hybridization and chromogenic in situ hybridization but not silver in situ hybridization (SISH). Aim: The purpose was to report chromosome 7 aberrations in ccRCC and pRCC using SISH in paraffi nembedded tissues and determine the association between the anomalies with clinical and pathological features. Materials and Methods: Cases of ccRCC and pRCC from University Malaya Medical Centre (2001-2009) were analyzed. Chromosome 7 staining was performed using an automated SISH method and association tests between chromosomal anomalies, clinical features and survival were performed. Results: SISH is a feasible technique to detect chromosome 7 aberration in RCC. Chromosome 7 aberrations with nuclear grading, staging and survival yielded no signifi cant correlation. Surprisingly, there was a signifi cant association between gender and chromosome 7 expressions. Though grade did not reach statistical signifi cance for survival in our RCC cases, there was a signifi cant correlation between overall survival with race and stage. Conclusion: Chromosome 7 aberrations in ccRCC showed no prognostic signifi cance. Nevertheless, staging and grading systems that include prognostic variables could hold better promise.

The Comparison of Automated Silver in situ Hybridization and Fluorescence in situ Hybridization for Evaluating HER2 Gene Amplification in Breast Carcinoma / 한국유방암학회지

PURPOSE: We want to validate the use of the silver-enhanced in situ hybridization (SISH) technique as comparised with fluorescence in situ hybridization (FISH) technique for assessing the HER2 gene amplification of breast carcinoma. METHODS: Tissue microarray (TMA) blocks from 58 breast cancer specimens were prepared and the concordance between HER2 gene amplification in breast cancer was determined by the FISH (PathVysion(R), Abbott/Vysis) technique and the automated silver in situ hybridization (SISH, INFORMtrade mark, Ventana) technique. For comparison, all the specimens were stained by immunohistochemistry (Ventana-PATHWAY(R)4B5). Evaluation was performed by two pathologists and with following the instructions of the manufacturers and the guidelines of the American Society of Clinical Oncology/College of American Pathologists. RESULTS: The results of SISH and FISH were identical in all 58 cases; 17 cases showed HER2 amplification, and on the other hand, 41 cases didn't show HER2 amplification. Five weakly positive (2+) cases in immunohistochemistry staining revealed one HER2 amplification and four no HER2 amplification on both SISH and FISH. The SISH results of the HER2/CEP17 ratio were well correlated with the FISH results of the HER2/CEP17 ratio (correlation coefficient r=0.745, Linear regression r2=0.555, p<0.001). CONCLUSION: The results of the SISH technique for assessing the HER2 status of excised breast carcinoma is comparable to the result obtained by FISH. However, SISH has the advantage of having permanent end result that can be visualized by an ordinary light microscope and less laborious preparation and time is needed than is required by FISH. SISH seems to be more feasible than FISH for assessing HER2 amplification of breast cancer.