Truchot Yohan, Dagher Elie, Abadie Jérôme, Nguyen Frédérique
AMaROC (Animal Cancers, Models for Research in Comparative Oncology), Oniris, Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, Nantes, France.
Université de Nantes, Inserm, CRCINA, Nantes, France.
Front Vet Sci. 2021 Jan 22;7:622019. doi: 10.3389/fvets.2020.622019. eCollection 2020.
Sex-determining Region Y (SRY)-box transcription factor-2 (Sox2) belongs to the "Yamanaka's factors," necessary and sufficient to convert somatic cells into pluripotent stem cells. In breast cancers, Sox2 expression has been associated with poor prognosis, and resistance to therapy. The aims of this study were to determine the frequency of Sox2 positivity in feline invasive mammary carcinomas (FMCs), its relationships with other clinical-pathologic variables, and with patient outcomes. This study relies on a previously described retrospective cohort of 180 FMCs, diagnosed in female cats treated by mastectomy alone, with 2-year follow-up. Sox2 (clone SP76), Estrogen Receptor alpha (ER), Progesterone Receptor (PR), Ki-67, Human Epidermal growth factor Receptor 2 (HER2), Androgen Receptor (AR), Bcl-2, Forkhead box protein A1 (FOXA1), basal markers and FoxP3-positive regulatory T cells (Tregs) were detected by automated immunohistochemistry. Sox2 expression was quantitated as an index (percentage of neoplastic cells demonstrating a positive nuclear signal). The FMCs were considered Sox2-positive at threshold >42%. Sox2 was not expressed in the normal mammary gland or in mammary hyperplasia without atypia, but was occasionally detected in atypical hyperplasia. In FMCs, the mean Sox2 index was 38 ± 30%, and 79/180 FMCs (44%) were Sox2-positive. Sox2 expression was associated with older age at diagnosis, lymphovascular invasion, high Ki-67 proliferation indexes, low PR and FOXA1 expression, and increased numbers of tumor-associated Tregs, but was not significantly associated with the clinical stage, histological types, and histological grade. By multivariate survival analysis, Sox2 was associated with poor cancer-specific survival (Hazard Ratio = 1.48, 95% confidence interval 1.04-2.11, = 0.0292), independently of the pathologic tumor size, pathologic nodal stage, distant metastasis, and AR expression. A rare subgroup of FMCs characterized by an AR+Sox2-phenotype (19/180 cases, 11%) was associated with very favorable outcomes. Sox2 expression was associated with poor cancer-specific survival of female cats with invasive mammary carcinomas, as previously reported in human breast cancer, but was more commonly expressed in cats than reported in breast cancers. Sox2 showed complementarity with AR in FMC prognostication.
性别决定区Y（SRY）-盒转录因子2（Sox2）属于“山中因子”，是将体细胞转化为多能干细胞所必需且充分的条件。在乳腺癌中，Sox2表达与预后不良及治疗耐药相关。本研究的目的是确定猫浸润性乳腺癌（FMC）中Sox2阳性的频率，其与其他临床病理变量的关系以及与患者预后的关系。本研究基于先前描述的180例FMC的回顾性队列，这些病例来自仅接受乳房切除术治疗的雌性猫，并进行了2年随访。通过自动免疫组织化学检测Sox2（克隆SP76）、雌激素受体α（ER）、孕激素受体（PR）、Ki-67、人表皮生长因子受体2（HER2）、雄激素受体（AR）、Bcl-2、叉头框蛋白A1（FOXA1）、基底标志物和FoxP3阳性调节性T细胞（Tregs）。Sox2表达定量为一个指数（显示阳性核信号的肿瘤细胞百分比）。当阈值>42%时，FMC被认为是Sox2阳性。Sox2在正常乳腺或无异型性的乳腺增生中不表达，但偶尔在非典型增生中检测到。在FMC中，Sox2平均指数为±30%，180例FMC中有79例（44%）为Sox2阳性。Sox2表达与诊断时年龄较大、淋巴管浸润、高Ki-67增殖指数、低PR和FOXA1表达以及肿瘤相关Tregs数量增加相关，但与临床分期、组织学类型和组织学分级无显著相关性。通过多因素生存分析，Sox2与癌症特异性生存率低相关（风险比=1.48，95%置信区间1.04-2.11，=0.0292），独立于病理肿瘤大小、病理淋巴结分期、远处转移和AR表达。一小部分罕见的FMC亚组具有AR+Sox2表型（180例中有19例，11%）与非常好的预后相关。Sox2表达与浸润性乳腺癌雌性猫的癌症特异性生存率低相关，正如先前在人类乳腺癌中报道的那样，但在猫中比在乳腺癌中更常见。在FMC预后评估中，Sox2与AR表现出互补性。
