Vanden Bempt Isabelle, Van Loo Peter, Drijkoningen Maria, Neven Patrick, Smeets Ann, Christiaens Marie-Rose, Paridaens Robert, De Wolf-Peeters Christiane
Department of Pathology, Katholieke Universiteit Leuven, Leuven, Belgium.
J Clin Oncol. 2008 Oct 20;26(30):4869-74. doi: 10.1200/JCO.2007.13.4296. Epub 2008 Sep 15.
Polysomy 17 is frequently found in breast cancer and may complicate the interpretation of HER-2 testing results. We investigated the impact of polysomy 17 on HER-2 testing and studied its clinicopathologic significance in relation to HER2 gene amplification.
In 226 patients with primary invasive breast carcinoma, HER2 gene and chromosome 17 copy numbers were determined by dual-color fluorescent in situ hybridization (FISH). The interpretation of FISH results was based on either absolute HER2 gene copy number or the ratio HER2/chromosome 17. Results were correlated with HER-2 protein expression on immunohistochemistry (IHC), HER2 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), and with various clinicopathologic parameters.
All cases with an equivocal HER-2 result by FISH, either by absolute HER2 copy number (44 of 226 patients; 19.5%) or by the ratio HER2/chromosome 17 (three of 226 patients; 1.3%), displayed polysomy 17. On its own, polysomy 17 was not associated with HER-2 overexpression on IHC or increased HER2 mRNA levels by RT-PCR. Moreover, and in contrast with HER2 gene amplification, polysomy 17 was not associated with high tumor grade, hormone receptor negativity, or reduced disease-free survival.
Polysomy 17 affects HER-2 testing in breast cancer and is a major cause of equivocal results by FISH. We show that tumors displaying polysomy 17 in the absence of HER2 gene amplification resemble more HER-2-negative than HER-2-positive tumors. These findings highlight the need for clinical trials to investigative whether polysomy 17 tumors benefit from HER-2-targeted therapy.
17号染色体多体性在乳腺癌中经常被发现，可能会使HER-2检测结果的解释复杂化。我们研究了17号染色体多体性对HER-2检测的影响，并研究了其与HER2基因扩增相关的临床病理意义。
对226例原发性浸润性乳腺癌患者，采用双色荧光原位杂交（FISH）检测HER2基因和17号染色体的拷贝数。FISH结果的判读基于HER2基因的绝对拷贝数或HER2/17号染色体的比值。结果与免疫组织化学（IHC）检测的HER-2蛋白表达、逆转录聚合酶链反应（RT-PCR）检测的HER2 mRNA表达以及各种临床病理参数相关。
所有FISH检测HER-2结果不明确的病例，无论是HER2拷贝数绝对值（226例患者中的44例；19.5%）还是HER2/17号染色体比值（226例患者中的3例；1.3%），均显示17号染色体多体性。单独来看，17号染色体多体性与IHC检测的HER-2过表达或RT-PCR检测的HER2 mRNA水平升高无关。此外，与HER2基因扩增相反，17号染色体多体性与高肿瘤分级、激素受体阴性或无病生存期缩短无关。
17号染色体多体性影响乳腺癌的HER-2检测，是FISH结果不明确的主要原因。我们发现，在没有HER2基因扩增的情况下显示17号染色体多体性的肿瘤更类似于HER-2阴性肿瘤而非HER-2阳性肿瘤。这些发现凸显了开展临床试验以研究17号染色体多体性肿瘤是否能从HER-2靶向治疗中获益的必要性。
