Abstract:
BACKGROUND:The role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS. METHODS:A well characterised DCIS cohort (n = 700) with long-term follow-up comprising pure DCIS (n = 508) and DCIS mixed with invasive carcinoma (IBC; n = 192) were stained immunohistochemically for CD20, CD3, CD4, CD8, FOXP3, PD1 and PDL1. Copy number variation and TP53 mutation status were assessed in a subset of cases (n = 58). RESULTS:CD3+ lymphocytes were the predominant cell subtype in the pure DCIS cohort, while FOXP3 showed the lowest levels. PDL1 expression was mainly seen in the stromal TILs. Higher abundance of TILs subtypes was associated with higher tumour grade, hormone receptor negativity and HER2 positivity. Mutant TP53 variants were associated with higher levels of stromal CD3+, CD4+ and FOXP3+ cells. DCIS coexisting with invasive carcinoma harboured denser stromal infiltrates of all immune cells and checkpoint proteins apart from CD4+ cells. Stromal PD1 was the most differentially expressed protein between DCIS and invasive carcinoma (Z = 5.8, p < 0.0001). Dense TILs, stromal FOXP3 and PDL1 were poor prognostic factors for DCIS recurrence, while dense TILs were independently associated with poor outcome for all recurrences (HR = 7.0; p = 0.024), and invasive recurrence (HR = 2.1; p = 0.029). CONCLUSIONS:Immunosuppressive proteins are potential markers for high risk DCIS and disease progression. Different stromal and intratumoural lymphocyte composition between pure DCIS, DCIS associated with IBC and invasive carcinoma play a potential role in their prognostic significance and related to the underlying genomic instability. Assessment of overall TILs provides a promising tool for evaluation of the DCIS immune microenvironment.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Toss MS,Abidi A,Lesche D,Joseph C,Mahale S,Saunders H,Kader T,Miligy IM,Green AR,Gorringe KL,Rakha EAdoi
10.1038/s41416-020-0797-7subject
Has Abstractpub_date
2020-05-01 00:00:00pages
1496-1506issue
10eissn
0007-0920issn
1532-1827pii
10.1038/s41416-020-0797-7journal_volume
122pub_type
杂志文章abstract::For stage III non-small cell lung cancer (NSCLC), approximately a third of patients survive up to 5 years, with decreasing 5-year survival rates for stage IIIB and stage IIIC disease. Although curable, stage III NSCLC encompasses a diverse range of disease presentation, with an equally complex range of multi-modal tre...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/s41416-020-01069-z
更新日期:2020-12-01 00:00:00
abstract::We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1704
更新日期:2001-04-06 00:00:00
abstract::In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumo...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.129
更新日期:1989-04-01 00:00:00
abstract:BACKGROUND:Tumours consist of heterogeneous cancer cells and are likely to contain drug-tolerant cell subpopulations, causing early relapse. However, treatment strategies to eliminate these cells have not been established. METHODS:We established gastric cancer patient-derived cells (PDCs) to examine the contribution o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0600-9
更新日期:2019-11-01 00:00:00
abstract::The aetiologic fractions due to smoking and chewing tobacco have been quantified for the first time, for cancers of the oral cavity, oropharynx, hypopharynx, larynx and oesophagus. The overall aetiologic fractions due to smoking and/or chewing tobacco have been found to be 70% for cancer of the oral cavity, 84% for th...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.31
更新日期:1977-02-01 00:00:00
abstract::One hundred resected cases of squamous cell carcinomas of the oesophagus were reviewed and a series of histological criteria related to the survival time. Two histological features were important in the assessment of survival. Good prognostic factors were a marked lymphocytic response to the tumour and a lack of intra...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.87
更新日期:1989-03-01 00:00:00
abstract:BACKGROUND:Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a la...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.567
更新日期:2014-12-09 00:00:00
abstract::Immunofluorescent assessment of hormone receptors in melanocytic tumours is quite feasible without loss of diagnostic material, in contrast to the impracticability of quantitative biochemical assays. Using this method, oestrogen receptors were demonstrated in 4/6, and progesterone receptors in 3/5 patients with metast...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.95
更新日期:1981-05-01 00:00:00
abstract:BACKGROUND:Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). METHODS:The national registry-based case-con...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.53
更新日期:2015-03-17 00:00:00
abstract:BACKGROUND:CYFRA 21-1 serves as biomarker in several epithelial malignancies. However, its role in pancreatic cancer (PC) has not yet been investigated. METHODS:Within a prospective single-centre study serial blood samples were collected from patients with confirmed advanced PC. Pre-treatment values and weekly measure...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.2013.158
更新日期:2013-04-30 00:00:00
abstract::In a population-based prospective study of 19,998 Japanese individuals, consumption of vegetables, green-yellow and green leafy vegetables was inversely associated with the risk of hepatocellular carcinoma (101 cases), with multivariable hazard ratios for the highest vs lowest tertile of 0.61 (95% confidence interval ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604843
更新日期:2009-01-13 00:00:00
abstract::Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant hepar...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600307
更新日期:2002-06-05 00:00:00
abstract:PURPOSE:To determine the feasibility of induction chemotherapy and chemo-IMRT in head and neck squamous cell cancers at risk of bilateral nodal spread (midline tumours) and to evaluate whether bilateral superficial lobe parotid-sparing IMRT can reduce the incidence of ⩾G2 subjective xerostomia. METHODS:Patients with m...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.553
更新日期:2015-01-06 00:00:00
abstract::To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.93
更新日期:1993-03-01 00:00:00
abstract::During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.270
更新日期:1986-12-01 00:00:00
abstract::Genomic alterations in the p53 tumour-suppressor gene and overexpression of p53 protein, resulting from gene mutations, are frequently found in pancreatic cancer. In this study we analysed the sera of 160 patients with malignant and benign pancreatic diseases for the presence of circulating antibodies to the p53 prote...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.443
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND:This study explored the association between smoking and colorectal malignant carcinoma (CRC) in the Chinese population at the national level for the first time. METHODS:In the China Nationwide Retrospective Mortality Survey conducted during 1989-1991, 12,942 CRC cases among 1,136,336 all-cause deaths aged ≥...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.9
更新日期:2014-03-04 00:00:00
abstract::The effects of X-radiation on the Nembutal-induced redistribution of the cardiac output in two types of transplanted mouse tumours and some normal mouse tissues have been investigated, using rubidium-86 and 125I-human serum albumin. Irradiation causes an increase in 86Rb uptake (relative blood perfusion) by the tumour...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1976.186
更新日期:1976-10-01 00:00:00
abstract:BACKGROUND:defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/sj.bjc.6605966
更新日期:2010-12-07 00:00:00
abstract:BACKGROUND:Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss of chromosomes during mitosis. Excessive levels of CIN can suppress tumour growth, providing a possible therapeutic strategy. The Mps1/TTK kinase has been one of the prime targets to explore this concept, ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0081-2
更新日期:2018-06-01 00:00:00
abstract::This study addresses the hypothesis that altered expression of oestrogen receptor-beta and/or altered relative expression of coactivators and corepressors of oestrogen receptors are associated with and may be mechanisms of de novo tamoxifen resistance in oestrogen receptor positive breast cancer. All cases were oestro...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600654
更新日期:2002-12-02 00:00:00
abstract::Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123I and 125I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at variou...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1982.157
更新日期:1982-07-01 00:00:00
abstract::In the district of Srikakulam in Andhra Pradesh in South India the habit of reverse smoking is widespread. In a house to house survey of oral cancer and precancerous conditions, comprising 10,169 villagers, 43·8% were reverse smokers; the female: male ratio being 1·7: 1. Ten previously undiagnosed cases of oral cancer...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1971.2
更新日期:1971-03-01 00:00:00
abstract:BACKGROUND:The 1997 international consensus conference on renal cell cancer (RCC) prognosis suggested erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), and anaemia as prognostic biomarkers, but most studies reviewed were limited by small sample sizes. METHODS:The Cox proportional hazards model was used...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.565
更新日期:2013-02-05 00:00:00
abstract::In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell l...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.55
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND:Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironm...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.517
更新日期:2012-01-03 00:00:00
abstract::During the period from 1950 to 1952, three patients were studied by electrophoresis according to Tiselius on account of anticomplementary activity at WR; the presence of an M-component was demonstrated. On several later occasions it was observed that this component at first seemed to remain unchanged, later it was sli...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1971.53
更新日期:1971-09-01 00:00:00
abstract:BACKGROUND:Most studies use hospital data to calculate postoperative complication rates (PCRs). We report on improving PCR estimates through use of patient-reporting. METHODS:A prospective cohort study of major surgery performed at 10 UK gynaecological cancer centres was undertaken. Hospitals entered the data contempo...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2013.366
更新日期:2013-08-06 00:00:00
abstract::Thirty-three patients with squamous cell carcinoma of the head and neck region were studied concerning p53 protein expression and mutations in exons 4-9 of the p53 gene using immunohistochemistry, polymerase chain reaction (PCR)-single strand conformation polymorphism analysis and DNA sequencing. Immunoreactivity was ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.159
更新日期:1995-04-01 00:00:00
abstract::A central role in anal carcinogenesis of high-risk types of human papillomaviruses (hrHPV) was recently established, but the possible role of benign anal lesions has not been addressed in hrHPV-positive and -negative anal cancers. As part of a population-based case-control study in Denmark and Sweden, we interviewed 4...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.719
更新日期:1998-12-01 00:00:00