Heublein Sabine, Page Sabina K, Mayr Doris, Ditsch Nina, Jeschke Udo
Department of Obstetrics and Gynaecology - National Center for Tumor Diseases (NCT), Heidelberg University Hospital, Heidelberg, Germany.
Department of Obstetrics and Gynaecology, Ludwig Maximilians University of Munich, Munich, Germany.
J Cancer Res Clin Oncol. 2016 Jun;142(6):1163-70. doi: 10.1007/s00432-016-2126-3. Epub 2016 Mar 2.
The oncofoetal Thomsen-Friedenreich (TF1, CD176) epitope is a carbohydrate cancer stem cell (CSC) antigen, and TF1-mediated cancer progression can be widely reversed by anti-TF1 antibodies. Particularly, CSC-like cells are regarded to be tumorigenic and chemoresistant. Aberrant p53 is probably the factor most closely associated with chemoresistance and tumour aggressiveness in ovarian tumours. We thus questioned whether TF1 in combination with p53 or as a single marker may be related to clinico-pathological features and survival of ovarian cancer patients.
Both markers were quantified in ovarian cancer tissue (n = 151) by immunohistochemistry. p53 staining was subdivided into three subgroups [n (completely negative) = 57, n (moderately stained) = 28, n (overexpressing) = 66]. TF1 was scored as positive (n = 30) versus negative (n = 121).
Only in those cancers classified with moderate p53 staining-and thus most likely displaying with wild-type TP53-TF1 positivity turned out to be a predictor for shortened overall survival (univariate: p < 0.001, multivariate: p = 0.001). By screening 17 different protein markers for correlation with TF1, only mucin-1 emerged as a potential TF1 carrier protein.
It is hypothesized that TF1 may confer tumour-promoting features, especially in a TP53 wild-type genetic background. In addition, TF1 is an attractive immunotherapeutic target. Whether those cases classified as TF1 positive and at the same time as moderately stained for p53 might particularly benefit from a future anti-TF1 antibody treatment or from TF1 vaccination therapy remains to be determined.
癌胚性Thomsen-Friedenreich（TF1，CD176）表位是一种碳水化合物癌干细胞（CSC）抗原，抗TF1抗体可广泛逆转TF1介导的癌症进展。特别是，CSC样细胞被认为具有致瘤性和化疗抗性。p53异常可能是与卵巢肿瘤化疗抗性和肿瘤侵袭性最密切相关的因素。因此，我们质疑TF1与p53联合或作为单一标志物是否可能与卵巢癌患者的临床病理特征和生存相关。
通过免疫组织化学对151例卵巢癌组织中的两种标志物进行定量分析。p53染色分为三个亚组[n（完全阴性）=57，n（中度染色）=28，n（过表达）=66]。TF1评分分为阳性（n=30）和阴性（n=121）。
仅在那些p53染色为中度的癌症中，也就是最有可能显示野生型TP53的癌症中，TF1阳性被证明是总生存期缩短的一个预测指标（单因素分析：p<0.001，多因素分析：p=0.001）。通过筛选17种不同的蛋白质标志物与TF1的相关性，只有粘蛋白-1被发现是一种潜在的TF1载体蛋白。
据推测，TF1可能赋予肿瘤促进特性，尤其是在TP53野生型基因背景下。此外，TF1是一个有吸引力的免疫治疗靶点。那些被归类为TF1阳性且同时p53染色为中度的病例是否可能特别受益于未来的抗TF1抗体治疗或TF1疫苗治疗仍有待确定。
