Evaluation of HER2 Protein Expression in Gastric Carcinomas: Comparative Analysis of 1414 Cases of Whole-Tissue Sections and 595 Cases of Tissue Microarrays
Evaluation of HER2 Protein Expression in Gastric Carcinomas: Comparative Analysis of 1414 Cases of Whole-Tissue Sections and 595 Cases of Tissue Microarrays
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DOI：
10.1245/s10434-011-1695-2
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发表时间：
2011-10-01
影响因子：
3.7
通讯作者：
Park, Young Soo
中科院分区：
文献类型：
--
作者：
Kim, Kab Choong;Koh, Young Wha;Park, Young Soo
背景。近年来分子靶向治疗的进展已经确定HER2是胃癌（GC）抗癌治疗的重要靶点。尽管HER2在乳腺癌中的临床相关性和预后意义已得到公认，但在gc中仍存在争议。免疫组化染色检测两个独立系列GC中HER2的表达。一个序列对应于1414例全组织切片，另一个序列对应于595例组织微阵列（tma）。结果与临床病理参数进行比较和相关性分析。在12.3%的全组织切片和17%的tma中检测到her2阳性。在评分为3+的样本中，90.1%的样本在肿瘤面积的千分之一的范围内染色，而在评分为2+的样本中，只有40.9%的样本在肿瘤面积的千分之一的范围内染色。在全组织切片中，her2阳性与年龄（P = 0.002）、组织学类型（分化型或肠型，P < 0.001）、淋巴血管浸润（P = 0.005）和淋巴结转移（P = 0.009）相关。在TMAs中，her2阳性仅与年龄（P = 0.003）和组织学类型（P < 0.001）相关。不同GC亚组的多因素分析显示her2阳性是独立的不良预后因素（P = 0.042）。her2阳性占肿瘤面积的千分之一（50%）的患者预后较肿瘤面积< 50%的患者差（P = 0.021）。尽管全组织切片和TMAs的结果存在差异，但HER2过表达与侵袭性生物学行为呈正相关，并且是分化型GCs复发的独立不良预后因素。因此，her2阳性GCs应考虑辅助曲妥珠单抗治疗。
Background. Recent advances in molecular targeted therapy have identified HER2 as an important target for anti-cancer therapy in gastric cancer (GC). Although the clinical relevance and prognostic significance of HER2 in breast cancer has been well acknowledged, it remains controversial in GC.Methods. HER2 expression was investigated in two independent series of GC by immunohistochemical staining. One series corresponded to 1,414 cases of whole-tissue sections and the other corresponded to 595 cases of tissue microarrays (TMAs). Results were compared and correlated with clinicopathologic parameters.Results. HER2-positivity was detected in 12.3% of whole-tissue sections and 17% of TMAs. Among samples scored 3+, 90.1% stained a parts per thousand yen50% of the tumor area, but only 40.9% in score 2+ cases stained a parts per thousand yen50% of the tumor area. In whole-tissue sections, HER2-positivity was correlated with age (P = 0.002), histological type (differentiated or intestinal, P < 0.001), lymphovascular invasion (P = 0.005), and lymph node metastasis (P = 0.009). In TMAs, HER2-positivity was correlated only with age (P = 0.003) and histological type (P < 0.001). Multivariate analyses of the differentiated GC subgroup revealed that HER2-positivity was an independent poor prognostic factor (P = 0.042). The cases with HER2-positive in a parts per thousand yen50% of the tumor area showed worse prognosis than those of < 50% (P = 0.021).Conclusions. Despite discrepancies in the results from whole-tissue sections and TMAs, HER2 overexpression was positively correlated with aggressive biological behavior and was an independent poor prognostic factor for recurrence in differentiated GCs. Therefore, HER2-positive GCs should be considered for adjuvant trastuzumab therapy.