The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer
Chang Lim Hyun 1, Hee Eun Lee 2, Ku Sang Kim 3, Sung-Won Kim 3, Jee Hyun Kim 4, Gheeyoung Choe 2 and So Yeon Park 2*
1 Department of Pathology, Seoul National University College of Medicine, Korea, Republic of
2 Department of Pathology, Seoul National University Bundang Hospital, Korea, Republic of
3 Department of Surgery, Seoul National University Bundang Hospital, Korea, Republic of
4 Department of Internal Medicine, Seoul National University Bundang Hospital, Korea, Republic of
* To whom correspondence should be addressed. E-mail: sypmd{at}snubh.org.
Accepted 15 August 2007
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Abstract |
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Aim: To investigate the effect of polysomy 17 on HER-2 status as evaluated by immunohistochemistry (IHC), dual-color fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH).
Methods: We performed dual-probe FISH and single-probe CISH to detect HER-2 gene amplification, and IHC to detect HER-2 expression, on 309 invasive breast cancers.
Results: Polysomy 17 was detected in 32.0% of the total number of breast cancers; it was detected in 12.3% of the IHC 0 or 1+ cases, 42.8% of the IHC 2+ cases and 66.0% of the IHC 3+ cases (P<0.001). In addition, there was a substantially higher rate of polysomy 17 in the IHC 2+ or 3+ /FISH-negative cases than in the IHC 0 or 1+ cases (40.8% vs. 12.3%; P<0.001). The FISH and CISH results were concordant in 299 cases (96.8%). Of the ten discordant cases, FISH suggested amplification in five with disomy 17 and one with monosomy 17, whereas CISH pointed to borderline copy numbers in each of these six cases. The remaining four cases had high polysomy 17, and CISH, but not FISH, indicated amplification.
Conclusions: These results suggest that an increase of HER-2 gene copy number secondary to polysomy 17 leads to HER-2 overexpression in some IHC 2+ / 3+ breast cancers, without gene amplification. The high level of concordance between FISH and CISH suggests that CISH is a valid alternative to FISH for assessing HER-2 gene amplification. However, cases in which CISH indicates the presence of borderline copy numbers or low levels of amplification may need FISH to rule out polysomy 17 and to determine HER-2 gene amplification status accurately.
Key Words:
HER-2, chromogenic in situ hybridization, fluorescence in situ hybridization, immunohistochemistry, polysomy 17
