In situ analysis of HER2 mRNA in gastric carcinoma: comparison with fluorescence in situ hybridization, dual-color silver in situ hybridization, and immunohistochemistry.
The importance of anti-HER2 therapy has focused attention on the ability of clinical assays to correctly assign HER2 amplification status. In the present study, we evaluated HER2 mRNA expression using a new mRNA in situ detection technique called RNAscope in 211 cases of formalin-fixed, paraffin-embedded gastric carcinoma. In addition, we compared the results with the conventional methods of immunohistochemistry, fluorescence in situ hybridization, and dual-color silver in situ hybridization. RNA in situ hybridization (in situ hybridization) showed that 162 cases (76.8%) were score 0, 5 cases (2.4%) were score 1, 10 cases (4.7%) were score 2, 13 cases (6.2%) were score 3, and 21 cases (10.0%) were score 4. HER2 transcription levels were found to be significantly related to pT class, pN class, and tumor recurrence. mRNA expression was well correlated with protein overexpression and gene amplification; 20 cases out of 23 with DNA amplification showed a score of 4 in RNA in situ hybridization (P < .001). Three cases showed false negative and one case showed false positive results by in situ hybridization. More studies are needed to determine whether the in situ hybridization method can identify additional patients that may benefit from anti-HER2 therapy or exclude those who may be resistant to anti-HER2 therapy.
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Min A
MA
Kim
Jung Eun
JE
Jung
Hee Eun
HE
Lee
Han-Kwang
HK
Yang
Woo Ho
WH
Kim
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012834:Silver / Q000737:chemistry; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D012834:Silver; C508053:ERBB2 protein, human