Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment. They may drive tumor progression, although the mechanisms involved are still poorly understood. Exosomes have emerged as important mediators of intercellular communication in cancer. They mediate horizontal transfer of microRNAs (miRs), mRNAs and proteins, thus affecting breast cancer progression. Differential expression profile analysis identified three miRs (miRs -21, -378e, and -143) increased in exosomes from CAFs as compared from normal fibroblasts. Immunofluorescence indicated that exosomes may be transferred from CAFs to breast cancer cells, releasing their cargo miRs. Breast cancer cells (BT549, MDA-MB-231, and T47D lines) exposed to CAF exosomes or transfected with those miRs exhibited a significant increased capacity to form mammospheres, increased stem cell and epithelial-mesenchymal transition (EMT) markers, and anchorage-independent cell growth. These effects were reverted by transfection with anti-miRs. Similarly to CAF exosomes, normal fibroblast exosomes transfected with miRs -21, -378e, and -143 promoted the stemness and EMT phenotype of breast cancer cells. Thus, we provided evidence for the first time of the role of CAF exosomes and their miRs in the induction of the stemness and EMT phenotype in different breast cancer cell lines. Indeed, CAFs strongly promote the development of an aggressive breast cancer cell phenotype.

Tumor response following preoperative chemoradiation therapy is mainly related to the preoperative regimen used. For patients receiving preoperative chemoradiation therapy, pretreatment T stage, but not tumor response to preoperative chemoradiation therapy, is prognostic for outcome (both disease-free and overall survival).

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Background: The cancer risk associated with gastric non-invasive neoplasia (formerly dysplasia) is debated. This prospective long term follow up study investigates the clinicopathological behaviour of non-invasive gastric neoplasia (and related lesions), focusing on the cancer risk associated with each different histological phenotype. Patients and methods: A total of 118 consecutive cases (nine indefinite for non-invasive neoplasia; 90 low grade non-invasive neoplasia; 16 high grade non-invasive neoplasia; and three suspicious for invasive adenocarcinoma) with a histological follow up of more than 12 months (average 52 months; range 12-206) were prospectively followed up with a standardised protocol. Patients in whom gastric cancer was detected within 12 months from the initial diagnosis of non-invasive neoplasia were excluded, assuming that invasive carcinoma had been missed at the initial endoscopy procedure. Results: Non-invasive neoplasia was no longer detectable in 57/118 cases (48%), was unchanged in 32 (30%), and evolved into gastric cancer in 20 patients (17%). Evolution to invasive adenocarcinoma was documented in both low and high grade non-invasive neoplastic lesions (8/90 low grade; 11/16 high grade) and correlated with histological severity (low versus high grade) at baseline (p<0.001). Seventy five per cent of cancers occurring during the long term follow up were stage I. Conclusions: The risk of invasive gastric cancer increases with the histological grade of the non-invasive neoplasia. Following up non-invasive gastric neoplasia increases the likelihood of gastric cancer being detected in its early stages.

Small cell carcinomas arising in salivary glands, extremely rare high-grade malignant tumors, are subclassified into neuroendocrine and ductal types. The neuroendocrine type may be segregated further into Merkel cell and pulmonary varieties according to cytokeratin 20 immunoreactivity. Whether subclassification of this tumor group has any biologic or clinical significance is not known. We examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma of major salivary glands from a single institution and analyzed their clinicopathologic profiles, including immunohistochemical features and prognostic factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive immunostaining, often with a paranuclear dotlike pattern of reactivity. All tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined, and 6 tumors were also positive for neurofilament, with a paranuclear dotlike pattern. Postoperatively, 9 patients developed metastatic disease, and 10 patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By log-rank analysis, overall survival was reduced significantly for patients with a primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for neuroendocrine markers (P = 0.034). These results indicate that small cell carcinoma of major salivary glands is a highly aggressive tumor, although the prognosis may be better than for extrasalivary neoplasms. Our data also suggest that most salivary gland small cell carcinomas exhibit neuroendocrine differentiation. Immunohistochemical expression of cytokeratin 20 can be used to classify salivary small cell carcinomas into Merkel cell and pulmonary types and may have prognostic significance.