Susan Pritchard

Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro-oesophageal junction cancers

Brown M, Sillah K, Griffiths E A, Swindell R, West C M, Page R D, Welch I M & Pritchard S A
(2010) Histopathology 56, 893–899
Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro‐oesophageal junction cancers

The degree of circumferential tumour involvement as a prognostic factor in oesophageal cancer.

OBJECTIVE Tumour length is an adverse prognostic factor in oesophageal cancer. However, the prognostic role of the degree of oesophageal circumference (DOC) involved by tumour with or without resection margin invasion is not clear. This work assessed the relationship between DOC involved by tumour, clinico-pathological variables and prognosis. METHODS The clinico-pathological details of 320 patients who underwent potentially curative oesophagogastrectomy for cancer between 1994 and 2007 were analysed. The DOC involved with tumour measured macroscopically on the resected specimen was classified as small (<2.5 cm, n = 115), large (> or = 2.5 cm, n = 144) or circumferential (i.e. involving the whole circumference, n = 61). Univariate and multivariate survival analyses were carried out. RESULTS The DOC with tumour was higher in ulcerating tumours than stenosing or polypoidal types (p = 0.017). Tumour length, T-stage, neoadjuvant chemotherapy and vascular invasion were independently associated with DOC with tumour on multivariate analysis (p < 0.05 for all). DOC > or = 2.5 cm was an adverse prognostic factor in univariate analysis (p = 0.002) with a hazard ratio of 1.52 [95% CI 1.13-2.04] compared with those <2.5 cm. Circumferential tumours had a similar prognosis to tumours > or = 2.5 cm (p = 0.60). The prognostic significance of DOC with tumour was lost in multivariate analysis where the factors retaining independence were patient age, T-stage, lymph node metastasis, vascular invasion and positive resection margins. However, when patients were stratified by use of neoadjuvant chemotherapy (n = 121), the DOC with tumour retained prognostic significance on multivariate analysis in the 199 patients who did not undergo neoadjuvant chemotherapy (p = 0.04). CONCLUSION The DOC with tumour appears to provide prognostic information in oesophageal cancer surgery, especially in patients who do not undergo preoperative chemotherapy.

Computed tomography overestimation of esophageal tumor length: Implications for radiotherapy planning

AIM To assess the relationship between preoperative computed tomography (CT) and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data. METHODS A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy. Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens. Inter- and intra-observer variations in CT measurements were assessed. Survival data were collected. RESULTS There was a weak correlation between CT and pathological tumor length (r = 0.30, P = 0.025). CT lengths were longer than pathological lengths in 68% (38/56) of patients with a mean difference of 1.67 cm (95% CI: 1.18-2.97). The mean difference in measurements by two radiologists was 0.39 cm (95% CI: -0.59-1.44). The mean difference between repeat CT measured tumor length (intra-observer variation) were 0.04 cm (95% CI: -0.59-0.66) and 0.47 cm (95% CI: -0.53-1.47). When stratified, patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length (r = 0.69, P = 0.0014, n = 37) than patients that did (r = 0.13, P = 0.43, n = 19). Median survival with CT tumor length > 5.6 cm was poorer than with smaller tumors, but the difference was not statistically significant. CONCLUSION Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions, particularly for planning radiotherapy.

Challenges in enumeration of CTCs in breast cancer using techniques independent of cytokeratin expression

Introduction Given the current postulated plasticity between epithelial and mesenchymal states of migratory cancer cells the detection of non-epithelial CTCs is an important scientific and clinical goal. Methods We used the filtration-based ISET technology to enrich circulating tumour cells (CTCs) in early breast cancer blood samples and identify them using a morphology-based immunocytochemistry (ICC) approach. Results We found greater numbers of putative CTCs by this approach than by the cytokeratin-based CellSearch technology, but a high number of CTC false positives were identified in healthy volunteer samples which were not reduced in successive blood draws. Preliminary work using an oestrogen receptor (ER)-based multiplex ICC method in metastatic breast cancer ISET samples indicated a low number of ER+ CTCs even at this advanced stage. Conclusions This work highlights the challenges in enumerating CTCs without conventional epithelial markers.

Abstract P6-08-30: The thrombin clotting pathway is upregulated in the stroma of pre-invasive breast cancer and further upregulated in aggressive invasive breast cancer phenotypes

BACKGROUND Components of the thrombin (extrinsic) clotting pathway are upregulated in cancer. The clotting pathway factors tissue factor (TF) and Thrombin promote tumour progression through protease activated receptors PAR2 and PAR1 respectively. AIMS To determine if tumour expression (epithelial and stromal) of a procoagulant phenotype is associated with aggressive breast cancer phenotypes and reduced survival. METHODS Tumour expression of TF, thrombin, PAR1 and PAR2 was determined by immunohistochemistry in two cohorts. PROSPECTIVE STUDY Early invasive breast cancer (n=199), ductal carcinoma in situ (DCIS, n=42) and normal breast tissue samples (n=121). RETROSPECTIVE STUDY Early invasive breast cancer patients (n=144) with median follow-up of 69 (range 4 to 91) months. Procoagulant phenotype expression was correlated with tumour grade, proliferation (Ki67), ER and HER2 status (both cohorts), survival and recurrence (retrospective cohort). RESULTS PROSPECTIVE STUDY Epithelium Thrombin (p Stroma TF, Thrombin, PAR1 and PAR2 were increased in the stroma of DCIS compared to normal breast stroma (p In invasive breast cancer, TF was increased in invasive cancer compared to DCIS and compared to normal breast tissue (p TF, thrombin, PAR1 and PAR2 were increased in high proliferating (p RETROSPECTIVE STUDY Stroma As with the prospective study, thrombin and PAR2 expression was increased in high proliferating cancer (p Overall (OS) and disease-free survival (DFS) PAR1 stromal expression was an independent predictor of reduced OS (HR 3.3, 95% CI 1.3-8.3, p=0.01) but did not correlate with DFS. There was no association between epithelial PAR1 expression or epithelial or stromal TF, thrombin or PAR2 expression and DFS or OS. CONCLUSION Stromal upregulation of the thrombin pathway occurs in in-situ cancer, implying cancer-stromal communication at the pre-invasive stage. Stromal thrombin pathway components may have a role in the transition of pre-invasive to invasive cancer. Stromal (but not epithelial) thrombin pathway upregulation is associated with aggressive invasive breast cancer phenotypes and reduced survival. The thrombin pathway may provide a novel therapeutic target, particularly in ER negative, HER2 positive breast cancer. Citation Format: Hudhaifah Shaker, Nigel J Bundred, Harith Albadry, Sarah L Nicholson, Susan Pritchard, Karin Jirstrom, Goran Landberg, Cliona C Kirwan. The thrombin clotting pathway is upregulated in the stroma of pre-invasive breast cancer and further upregulated in aggressive invasive breast cancer phenotypes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-30.