Gujam F J A, Edwards J, Mohammed Z M A, Going J J, McMillan D C
Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences-University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK.
Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences-University of Glasgow, Western Infirmary, Glasgow, UK.
Br J Cancer. 2014 Jul 8;111(1):157-65. doi: 10.1038/bjc.2014.279. Epub 2014 May 29.
The percentage of tumour stroma (TSP) has recently been reported to be a novel independent predictor of outcome in patients with a variety of common solid organ tumours. The aim of this study was to examine the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease.
A total of 361 patients with primary operable invasive ductal breast cancer were included in this study. The TSP was assessed visually on the haematoxylin and eosin-stained tissue sections. With a cutoff value of 50% TSP, patients with ≤ 50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group.
A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had more Her-2-positive tumours (P=0.029), low-grade tumour inflammatory infiltrate (P=0.034), low CD68+macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter cancer-specific survival (P<0.001). In node-negative patients (n=207), high TSP was associated with low CD68+macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter cancer-specific survival (P=0.005). In triple negative patients (n=151), high TSP was associated with high tumour grade (P=<0.001), lymph node positivity (P=0.027), low CD68+macrophage infiltrate (P=0.011) and shorter cancer-specific survival (P=0.035). The 15-year cancer-specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. In multivariate survival analysis, a high TSP was associated with reduced cancer-specific survival in the whole cohort (P=0.001), node-negative patients (P=0.007) and those who received systemic adjuvant therapy (P=0.021), independent of other pathological characteristics including host inflammatory response. However, TSP was not an independent prognostic factor for triple negative patients (P=0.151).
A high TSP in primary operable invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with primary operable ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with invasive ductal breast cancer.
最近有报道称,肿瘤间质百分比(TSP)是多种常见实体器官肿瘤患者预后的一种新型独立预测指标。本研究旨在探讨浸润性导管癌患者中TSP、临床病理特征与预后之间的关系,尤其是淋巴结阴性和三阴性疾病患者。
本研究共纳入361例原发性可手术浸润性导管癌患者。通过苏木精和伊红染色的组织切片对TSP进行视觉评估。以TSP 50%为临界值,基质≤50%的患者分为低TSP组,基质>50%的患者分为高TSP组。
共有109例(30%)患者TSP较高。TSP较高的患者年龄较大(P=0.035),Her-2阳性肿瘤较多(P=0.029),肿瘤炎症浸润分级较低(P=0.034),CD68+巨噬细胞浸润较低(P<0.001),CD4+较低(P=0.023),CD8+ T淋巴细胞浸润较低(P=0.017),肿瘤复发(P=0.015),癌症特异性生存期较短(P<0.001)。在淋巴结阴性患者(n=207)中,高TSP与低CD68+巨噬细胞浸润(P=0.001)、低CD4+(P=0.040)、低CD8+ T淋巴细胞浸润(P=0.016)及较短的癌症特异性生存期(P=0.005)相关。在三阴性患者(n=151)中,高TSP与高肿瘤分级(P<0.001)、淋巴结阳性(P=0.027)、低CD68+巨噬细胞浸润(P=0.011)及较短的癌症特异性生存期(P=0.035)相关。低TSP组与高TSP组的15年癌症特异性生存率分别为79%和21%。在多因素生存分析中,高TSP与整个队列(P=0.001)、淋巴结阴性患者(P=0.007)及接受全身辅助治疗的患者(P=0.021)的癌症特异性生存期缩短相关,且独立于包括宿主炎症反应在内的其他病理特征。然而,TSP并非三阴性患者的独立预后因素(P=0.151)。
原发性可手术浸润性导管癌中高TSP与复发及较差的长期生存相关。与肿瘤炎症浸润的负相关突出了肿瘤间质量在原发性可手术导管癌患者免疫反应中的重要性。在常规病理检查中采用这一简单且可重复的参数可能有助于优化浸润性导管癌患者的风险分层。