• Fumihiko Mitsui, Yoh Dobashi, Issei Imoto, Johji Inazawa, Koji Kono, Hideki Fujii, and Akishi Ooi.
• Department of Pathology, School of Medicine, University of Yamanashi, Yamanashi, Japan.
• Mod. Pathol. 2007 Jun 1; 20 (6): 622-31.

AbstractThis study was conducted to assess the frequencies of protein overexpression and gene amplification of Myc and to identify the mechanisms of Myc gene amplification, especially with regards to its possible coamplification with ERBB2 or EGFR in gastric adenocarcinomas. By immunohistochemical analysis of a total of 300 formalin-fixed and paraffin-embedded gastric adenocarcinomas, the nuclear overexpression of MYC was found in 47 tumors (16%). A fluorescence in situ hybridization (FISH) analysis revealed that nine (19%) of the 47 tumors with protein overexpression had cancer cells with high levels of Myc amplification, whereas only seven (6%) of the 122 tumors without protein overexpression showed high-level Myc gene amplification. Such Myc amplification was significantly correlated with positive nuclear protein overexpression. The coamplification of ERBB2 or EGFR with Myc that was found in six and four cases, respectively, is believed to be non-incidental because those frequencies were significantly higher than the individual frequencies observed for the total examined cases (ERBB2: 7%; EGFR: 4%). The high levels of gene amplification of these three genes, as visualized by FISH, could be broadly classified into two typical types, namely, 'multiple scattered signals' and 'large clustered signals'. Using two-color FISH, the coexistence of coamplified Myc and ERBB2, or Myc and EGFR, within single nuclei in various combinations of amplification types and copy numbers, could be ascertained in all nine cases, including one in which the synchronous 'multiple scattered type' coamplification of Myc and ERBB2 was observed. In three tumors, coamplification of ERBB2 and EGFR was found; however, ERBB2- and EGFR-amplified cell populations were separate and mutually exclusive. We propose that the non-incidental coamplification of Myc and either ERBB2 or EGFR occurred through translocation and subsequent rearrangement.

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