Background Intestinal metaplasia (IM) is a gastric cancer precursor lesion (GCPL), with the highest risk to progress to gastric cancer (GC). Clinical guidelines recommend gastroscopy every 3 years for extensive IM. Unfortunately, studies on protein biomarkers indicating a transition from IM to GC are lacking. We have recently found that the IFNα-responsive gene Schlafen 4 (Slfn4) present in immune cells correlates with metaplastic changes in Helicobacter-infected mice. Therefore we tested the hypothesis that a human homolog of Slfn4, which is Schlafen 5 (SLFN5) correlates with progression of GCPL to GC. Methods Jurkat T-lymphoid and HL-60 myeloid cell lines were treated with IFNα and SLFN5 mRNA was quantified by qPCR. SLFN5 protein expression in the inflamed gastric mucosa was co-localized to specific immune cell types by immunohistochemistry using CD20, CD2 and MAC2 antibodies. SLFN5 expression was also determined by immunohistochemistry in FFPE samples from individuals with non-atrophic, atrophic gastritis, complete and incomplete IM as well as GC. Results We demonstrated that IFNα treatment of Jurkat and HL-60 cells induced SLFN5 mRNA. SLFN5 protein was expressed mainly by T lymphocytes in inflamed gastric mucosa. The highest level of SLFN5 expression was observed in subjects with IM that progressed to GC. ROC curves demonstrated that combining SLFN5 expression with the histological diagnosis of IM significantly increased the probability of identifying patients that might progress to GC. Conclusion Elevated SLFN5 protein expression in subjects with IM correlated with progression to gastric cancer.

BackgroundIntestinal metaplasia (IM) is a precursor lesion that precedes gastric cancer (GC). There are two IM histological subtypes, complete (CIM) and incomplete (IIM), the latter having higher progression rates to GC. This study was aimed at analysing gene expression and molecular processes involved in the progression from normal mucosa to IM, and also from IM subtypes to GC.MethodologyWe used expression data to compare the transcriptome of healthy gastric mucosa to that of IM not progressing to GC, and the transcriptome of IM subtypes that had progressed to GC to those that did not progress. Some deregulated genes were validated and pathway analyses were performed.ResultsComparison of IM subtypes that had progressed to GC with those that did not progress showed smaller differences in the expression profiles than the comparison of IM that did not progress with healthy mucosa. New transcripts identified in IM not progressing to GC included TRIM, TMEM, homeobox and transporter genes and SNORD116. Comparison to normal mucosa identified non tumoral Warburg effect and melatonin degradation as previously unreported processes involved in IM. Overexpressed antigen processing is common to both IM-subtypes progressing to GC, but IIM showed more over-expressed oncogenic genes and molecular processes than CIM.ConclusionsThere are greater differences in gene expression and molecular processes involved in the progression from normal healthy mucosa to IM than from IM to gastric cancer. While antigen processing is common in both IM-subtypes progressing to GC, more oncogenic processes are observed in the progression of IIM.

Inflammatory myofibroblastic tumor (IMT) is a rare mass-forming lesion characterized by fibroblastic or myofibroblastic spindle cell proliferation with varying degrees of inflammatory cell infiltration. Although it has been reported in virtually every organ in the body, the lung is the most common site of involvement. Extrapulmonary IMTs, although rare, have been reported and are characterized by different, more aggressive behavior. We report an extremely rare case of maxillary metastases of pulmonary IMT. Lung IMT was initially misdiagnosed, and oral lesion mimicked clinically and radiologically a radicular cyst. On histologic examination, cells exhibited diffuse and intense immunoreactivity for α-smooth muscle actin and vimentin whereas both pulmonary and oral IMTs presented absence of cellular atypia and lack of expressivity of oncogenic determinants. Distant metastases of lung IMT are extremely unusual, and this is the first report to our knowledge with this particular clinical course. Despite the possibility that the present case could also represent a metachronous multifocal IMT, with pulmonary and extrapulmonary lesions, similar histopathological and immunohistochemical patterns in lung and maxillary region suggest a metastatic course.

Melanoma is the most lethal cutaneous cancer. New drugs have recently appeared; however, not all patients obtain a benefit of these new drugs. For this reason, it is still necessary to characterize melanoma at molecular level. The aim of this study was to explore the molecular differences between melanoma tumor subtypes, based on BRAF and NRAS mutational status. Fourteen formalin-fixed, paraffin-embedded melanoma samples were analyzed using a high-throughput proteomics approach, combined with probabilistic graphical models and Flux Balance Analysis, to characterize these differences. Proteomics analyses showed differences in expression of proteins related with fatty acid metabolism, melanogenesis and extracellular space between BRAF mutated and BRAF non-mutated melanoma tumors. Additionally, probabilistic graphical models showed differences between melanoma subgroups at biological processes such as melanogenesis or metabolism. On the other hand, Flux Balance Analysis predicts a higher tumor growth rate in BRAF mutated melanoma samples. In conclusion, differential biological processes between melanomas showing a specific mutational status can be detected using combined proteomics and computational approaches.

Sinus histiocytosis with massive lymphadenopathy, or Rosai-Dorfman disease (RDD), is commonly characterized by painless cervical lymphadenopathy. Exclusively cutaneous Rosai-Dorfman disease is rare. In the absence of massive lymphadenopathy, the nonspecific skin lesions may complicate the diagnosis. To our knowledge, the case reported herein is the youngest case of extranodal cutaneous RDD.

We report the case of a 6-month-old Hispanic boy with a 4-month history of widespread pruritic hypopigmented papules mimicking lichen nitidus. The final diagnosis was multisystem non-risk-organ Langerhans cell histiocytosis (LCH), with cutaneous and multiple bone involvement. With this patient and others previously reported in the literature, we suggest an early biopsy of the hypopigmented rash in children.

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