Erber Ramona, Kailayangiri Sareetha, Huebner Hanna, Ruebner Matthias, Hartmann Arndt, Häberle Lothar, Meyer Julia, Völkl Simon, Mackensen Andreas, Landgraf Laura, Geppert Carol I, Schulz-Wendtland Rüdiger, Beckmann Matthias W, Fasching Peter A, Farwick Nicole, Rossig Claudia, Gass Paul
Institute of Pathology, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
Department of Pediatric Hematology and Oncology, Münster University Hospital, 48149 Münster, Germany.
Cancers (Basel). 2021 Nov 8;13(21):5577. doi: 10.3390/cancers13215577.
The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and other solid tumors. We retrospectively investigated GD2 expression in a breast cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC ( = 568) and IF ( = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast cancer (TNBC) compared with other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast cancer cases, with the highest frequency in hormone receptor-positive tumors. With this high expression frequency, patients with GD2-positive advanced breast cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.
双唾液酸神经节苷脂GD2是一种肿瘤相关抗原，这可能使得针对神经母细胞瘤和其他实体瘤患者应用靶向免疫疗法（抗GD2抗体、GD2嵌合抗原受体T细胞）成为可能。我们使用组织微阵列（TMA）上的免疫组织化学（IHC）和免疫荧光（IF），回顾性研究了乳腺癌队列中GD2的表达情况及其对生存的影响。研究了IHC（n = 568）和IF（n = 503）上GD2的表达与亚型和患者预后的关系。总体而言，在568个经IHC评估的样本中，50.2%为GD2阳性，在503个经IF评估的样本中，69.8%为GD2阳性。在管腔型肿瘤中观察到GD2阳性肿瘤的比例最高。与其他亚型相比，三阴性乳腺癌（TNBC）中检测到的GD2阳性病例明显较少。在IF染色中（但在IHC中未观察到），与管腔型肿瘤相比，HER2阳性乳腺癌中表达GD2的肿瘤比例显著更低。在整个队列或各个亚型中，IHC或IF检测的GD2表达与无病生存期或总生存期均无显著相关性。然而，超过50%的乳腺癌病例中可检测到GD2表达，在激素受体阳性肿瘤中频率最高。鉴于这种高表达频率，所有亚型的GD2阳性晚期乳腺癌患者可能会从目前正在进行临床试验的靶向GD2免疫疗法中获益。
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