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J Korean Cancer Assoc > Volume 28(6); 1996 > Article
Journal of the Korean Cancer Association 1996;28(6): 996-1010.
유방암 조직에서 In Situ Hybridization 을 이용한 Epidermal Growth Factor Receptor mRNA 의 발현
이원종, 이수정, 김동석, 권굉보, 심민철
Expression of Epidermal Growht Factor Receptor mRNA by In Situ Hybridization in Breast Cancer
Won Jong Lee, Soo Jung Lee, Dong Sug Kim, Koing Bo Kwun, Min Chul Chim
Epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) have been identified as one of the prognostic factor for breast cancer. EGFR status has been determined by several methods including competitive binding assay(BA), immunohistochemical stain(IHC), enzyme immunoassay(EIA). But EGFR could be masked by endogenous ligands in some proportion of tumors. So many different methods have been developed to detect EGFR mRNA. Among these methods, in situ hybridization with biotinylated probe found to be simple and rapid. In addition, it can determine intratumoral heterogenicity in gene expression and identify specific cells that contain a particular mRNA transcript. The author investigated the expression of EGFR mRNA in 81 human breast cancers by in situ hybridization(ISH) and compared the result with EGFR detected by IHC. The author also examined the relationship between EGFR mRNA expression and clinical parameters and other prognostic markers(estrogen receptor, progesterone receptor, p53, c-erbB-2). The author also studied the relationship between EGFR mRNA and recurrence and mortality rate. According to the degree of cytoplasmic staining in ISH assay, negative were 13 cases(16.1%), + were 41 cases(50.6%), ++ were 26 cases(32.1%) and +++ was 1 case(1.2%). The overall expression of EGFR mRNA was 84%. The positive staining of EGFR by IHC was observed either on the cell membrane alone or on both cell membrane and cytoplasm. EGFR by IHC were detected in 69.l%. The 19 cases(23.5%) of EGFR negative cases by IHC were demonstrated as + or more EGFR mRNA by ISH study. On the contrary, 7 cases(8.6%) of EGFR positive by IHC were not detected by ISH. The findings in the majority of the cases were same in two methods. EGFR mRNA had shown a significant positive correlation with c-erbB-2(p<0.009). But an inverse correlation with both estrogen receptor(p<0.027) and progesterone receptor(p<0.02) status, when ++ or more were regarded as positive staining in ISH. There were no correlation was found between positive EGFR by IHC and clinical parameters and other prognostic markers except c-erbB-2(p<0.05). Among the 11 cases of tumor containing both invasive ductal carcinoma and ductal carcinoma in situ(DCIS), there were 5 cases of + and 4 cases of ++ in invasive ductal carcinoma, but negative in these cases of DCIS by ISH. Although the cases with overexpression of EGFR mRNA showed a tendency of more recurrent rate and mortality rate, but there were no statistic significance during the short follow up period (24 months). In summery, EGFR mRNA thought to be a useful prognostic factor especially when over expression is more than ++ by ISH. In situ mRNA hybridization technique is more sensitive and more accurate than immunohistochemistry.
Key words: Breast carcinoma, EGFR mRNA, In situ hybridization
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