Stroma AReactive Invasion Front Areas (SARIFA): a novel histopathologic biomarker in colorectal cancer patients and its association with the luminal tumour proportion

Background Stroma AReactive Invasion Front Areas (SARIFA) is a novel prognostic histopathologic biomarker measured at the invasive front in haematoxylin & eosin (H&E) stained colon and gastric cancer resection specimens. The aim of the current study was to validate the prognostic relevance of SARIFA-status in colorectal cancer (CRC) patients and investigate its association with the luminal proportion of tumour (PoT). Methods We established the SARIFA-status in 164 CRC resection specimens. The relationship between SARIFA-status, clinicopathological characteristics, recurrence-free survival (RFS), cancer-specific survival (CSS), and PoT was investigated. Results SARIFA-status was positive in 22.6% of all CRCs. SARIFA-positivity was related to higher pT, pN, pTNM stage and high grade of differentiation. SARIFA-positivity was associated with shorter RFS independent of known prognostic factors analysing all CRCs (RFS: hazard ratio (HR) 2.6, p = 0.032, CSS: HR 2.4, p = 0.05) and shorter RFS and CSS analysing only rectal cancers. SARIFA-positivity, which was measured at the invasive front, was associated with PoT-low (p = 0.009), e.g., higher stroma content, and lower vessel density (p = 0.0059) measured at the luminal tumour surface. Conclusion Here, we validated the relationship between SARIFA-status and prognosis in CRC patients and provided first evidence for a potential prognostic relevance in the subgroup of rectal cancer patients. Interestingly, CRCs with different SARIFA-status also showed histological differences measurable at the luminal tumour surface. Further studies to better understand the relationship between high luminal intratumoural stroma content and absence of a stroma reaction at the invasive front (SARIFA-positivity) are warranted and may inform future treatment decisions in CRC patients

Stroma AReactive Invasion Front Areas (SARIFA) improves prognostic risk stratification of perioperative chemotherapy treated oesophagogastric cancer patients from the MAGIC and the ST03 trial

Background Tumour-associated fat cells without desmoplastic stroma reaction at the invasion front (Stroma AReactive Invasion Front Areas (SARIFA)) is a prognostic biomarker in gastric and colon cancer. The clinical utility of the SARIFA status in oesophagogastric cancer patients treated with perioperative chemotherapy is currently unknown. Methods The SARIFA status was determined in tissue sections from patients recruited into the MAGIC (n = 292) or ST03 (n = 693) trials treated with surgery alone (S, MAGIC) or perioperative chemotherapy (MAGIC, ST03). The relationship between SARIFA status, clinicopathological factors, overall survival (OS) and treatment was analysed. Results The SARIFA status was positive in 42% MAGIC trial S patients, 28% MAGIC and 48% ST03 patients after pre-operative chemotherapy. SARIFA status was related to OS in MAGIC trial S patients and was an independent prognostic biomarker in ST03 trial patients (HR 1.974, 95% CI 1.555–2.507, p < 0.001). ST03 patients with lymph node metastasis (ypN + ) and SARIFA-positive tumours had poorer OS than patients with ypN+ and SARIFA-negative tumours (plogrank < 0.001). Conclusions The SARIFA status has clinical utility as prognostic biomarker in oesophagogastric cancer patients irrespective of treatment modality. Whilst underlying biological mechanisms warrant further investigation, the SARIFA status might be used to identify new drug targets, potentially enabling repurposing of existing drugs targeting lipid metabolism

P06.06 Enhancing trafficking and resistance to immunosuppression of synthetic agonistic receptor-transduced T cells in solid tumor models

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Erythematous capillary-lymphatic malformations mimicking blood vascular anomalies

Superficial erythematous cutaneous vascular malformations are assumed to be blood vascular in origin, but cutaneous lymphatic malformations can contain blood and appear red. Management may be different and so an accurate diagnosis is important. Cutaneous malformations were investigated through 2D-histology and 3D-whole-mount-histology. Two lesions were clinically considered as port-wine birthmark, and another three lesions as erythematous telangiectasias.The aims were: i) to prove that cutaneous erythematous malformations including telangiectasia can represent a lymphatic phenotype, ii) to determine if lesions represent expanded but otherwise normal or malformed lymphatics, and iii) to determine if the presence of erythrocytes explained the red colour. Microscopy revealed all lesions as lymphatic structures. Port-wine birthmarks proved to be cystic lesions, with non-uniform lymphatic marker expression, and a disconnected lymphatic network suggesting a lymphatic malformation. Erythematous telangiectasias represented expanded but non-malformed lymphatics. Blood within lymphatics appeared to explain the colour. Blood-lymphatic-shunts could be detected in the erythematous telangiectasia.In conclusion, erythematous cutaneous capillary lesions may be lymphatic in origin but clinically indistinguishable from blood vascular malformations. Biopsy is advised for correct phenotyping and management. Erythrocytes are the likely explanation for colour accessing lymphatics through lympho-venous-shunts

Synthesis, structure and pyrolysis of stabilised phosphonium ylides containing saturated oxygen heterocycles

yesA range of twelve stabilised phosphonium ylides containing tetrahydrofuran, tetrahydropyran or 2,2- dimethyl-1,3-dioxolane rings have been prepared and fully characterised, including one X-ray structure determination of each type. The X-ray structures confirm the PvC and CvO functions to be syn and all the compounds undergo thermal extrusion of Ph3PO to give the corresponding alkynes. In some cases there is also competing loss of Ph3P to give different carbene-derived products and evidence has been obtained for the generation of 2-phenyloxete in this way. Raising the pyrolysis temperature leads in several cases to new secondary reactions of the alkyne products involving a sequence of alkyne to vinylidene isomerisation, intramolecular CH insertion, and retro Diels Alder reaction

The dipolar endofullerene HF@C60

The cavity inside fullerenes provides a unique environment for the study of isolated atoms and molecules. We report encapsulation of hydrogen fluoride inside C60 using molecular surgery to give the endohedral fullerene HF@C60. The key synthetic step is the closure of the open fullerene cage while minimizing escape of HF. The encapsulated HF molecule moves freely inside the cage and exhibits quantization of its translational and rotational degrees of freedom, as revealed by inelastic neutron scattering and infrared spectroscopy. The rotational and vibrational constants of the encapsulated HF molecules were found to be redshifted relative to free HF. The NMR spectra display a large 1H-19F J coupling typical of an isolated species. The dipole moment of HF@C60 was estimated from the temperature-dependence of the dielectric constant at cryogenic temperatures and showed that the cage shields around 75% of the HF dipole