Abstract Background The diagnosis of breast cancer (BC)-related leptomeningeal metastases (LM) relies on the detection of tumor cells in cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, the sensitivity of this technique is low. Our goal was to evaluate whether circulating tumor cell (CTC) detection in CSF using the CellSearch® system could be used for LM diagnosis. Methods This prospective, monocentric study included adult patients with suspected BC-related LM. The clinical sensitivity and specificity of CTC detection in CSF for LM diagnosis were calculated relative to conventional CSF cytology. Results Forty-nine eligible patients were included and 40 were evaluable (CTC detection technical failure: n = 8, eligibility criteria failure: n = 1). Cytology was positive in 18/40 patients. CTCs were detected in these 18 patients (median: 5824 CTC, range: 93 to 45052) and in 5/22 patients with negative cytology (median: 2 CTC, range: 1 to 44). The detection of ≥1 CSF CTC was associated with a clinical sensitivity of 100% (95% CI, 82.4–100) and a specificity of 77.3% (95% CI, 64.3–90.3) for LM diagnosis. HER2+ CTCs were detected in the CSF of 40.6% of patients with HER2− BC (median: 500 CTC, range: 13 to 28 320). Conclusions The clinical sensitivity of CTC detection in CSF with the CellSearch® system for LM diagnosis is higher than that of CSF cytology. CTC detection in patients with negative cytology, however, must be further investigated. The finding of HER2+ CTCs in patients with HER2− BC suggests that the HER2 status of LM should be evaluated to increase the treatment opportunities for these patients.

Objectives During malignant transformation, remodeling of the extracellular matrix creates a stromal tumor microenvironment (TME) essential for cancer progression. Collagen is a main component of this TME and its relevance as an indicator of tumor transformation is highlighted in research on breast and prostate cancer. The most sensitive reported technology to study these collagenic architectural transformations is multiphoton microscopy (MPM), monitoring 2-photon excited fluorescence and second harmonic generation. The main objective of this work is to establish a proof of concept of MPM to better understand the TME processes underlying oral cancer (OC) and to support novel effective therapeutic strategies. The relevance of the topic gains its evidence from the current lack of effective prevention and curative treatment for this devastating cancer. Methods Cryostat-sectioned and paraffin-embedded samples were analyzed and the generated SHG images were recorded using a custom-made MPM based on a Tsunami laser and an upright SliceScope microscope furbished with a multiphoton galvanometer scan head. 38 samples, pertaining to 15 types of lesions representative of all tumor stages, were analyzed. 44% of samples (n=168) were usable. Results Results showed that collagen, normally well organized, deteriorates with tumour progression and gradually transforms into an increasingly disordered network, with fibers firstly dissociating and thinning. Analysis by vectorization of perilesional collagen fibers suggests, in invasive tumors, an organization of these fibers perpendicularly to the tumor, creating "gateways" for migration into surrounding tissues of tumor cells. The identification of the evolution of collagen density and organization seems to allow, as for other tumor localizations, to define a tumor-associated collagen signatures (TACS) gradation scale for OC, statistically correlated with overall and recurrence-free survival. Conclusions MPM could be a reliable tool in the identification of tumor progression markers of OC, which would be complementary to pathological examination and useful for identifying target areas for biopsy or surgical margins.

The π-conjugated polymer polydiphenylbutadiyne was prepared at the nanoscale confined inside the 1.2 nm 1-D pores of the aluminophosphate AlPO4-54. Molten 1,4-diphenyl-1,3-dibutadiyne (DPB) was inserted in the pores of AlPO4-54 at pressures below 0.3 GPa as confirmed by X-ray diffraction. Heating to 190 °C under a pressure of 0.4 GPa induced polymerization of DPB in the pores. Infrared microscopy indicates full polymerization in the pores and the presence of characteristic saturated C–H defects common to other nanostructured PDPB materials exhibiting important photocatalytic properties. This nanostructured PDPB confined in the hygroscopic AlPO4-54 host could be of interest for applications in gas sensing, photocatalysis and hydrogen generation.