Subtype-Specific Analyses Reveal Infiltrative Basal Cell Carcinomas Are Highly Interactive with their Environment.

Little is known regarding the molecular differences between basal cell carcinoma (BCC) subtypes, despite clearly distinct phenotypes and clinical outcomes. In particular, infiltrative BCCs have poorer clinical outcomes in terms of response to therapy and propensity for dissemination. In this project, we aimed to use exome sequencing and RNA sequencing to identify somatic mutations and molecular pathways leading to infiltrative BCCs. Using whole-exome sequencing of 36 BCC samples (eight infiltrative) combined with previously reported exome data (58 samples), we determine that infiltrative BCCs do not contain a distinct somatic variant profile and carry classical UV-induced mutational signatures. RNA sequencing on both datasets revealed key differentially expressed genes, such as POSTN and WISP1, suggesting increased integrin and Wnt signaling. Immunostaining for periostin and WISP1 clearly distinguished infiltrative BCCs, and nuclear ß-catenin staining patterns further validated the resulting increase in Wnt signaling in infiltrative BCCs. Of significant interest, in BCCs with mixed morphology, infiltrative areas expressed WISP1, whereas nodular areas did not, supporting a continuum between subtypes. In conclusion, infiltrative BCCs do not differ in their genomic alteration in terms of initiating mutations. They display a specific type of interaction with the extracellular matrix environment regulating Wnt signaling.

Frameshift mutation of WISP3 gene and its regional heterogeneity in gastric and colorectal cancers.

WISP3 is involved in many cancer-related processes including epithelial-mesenchymal transition, cell death, invasion, and metastasis and is considered a tumor suppressor. The aim of our study was to find whether WISP3 gene was mutated and expressionally altered in gastric (GC) and colorectal cancers (CRCs). WISP3 gene possesses a mononucleotide repeat in the coding sequence that could be mutated in cancers with high microsatellite instability (MSI-H). We analyzed 79 GCs and 156 CRCs, and found that GCs (8.8%) and CRCs (10.5%) with MSI-H, but not those with microsatellite stable/low MSI, harbored a frameshift mutation. We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the WISP3 mutation exhibited regional ITH in 25% of the CRCs. In immunohistochemistry, loss of WISP3 expression was identified in 24% of GCs and 21% of CRCs. The loss of expression was more common in those with WISP3 mutation than with wild-type WISP3 and those with MSI-H than with microsatellite stable/low MSI. Our data indicate that WISP3 harbored not only frameshift mutation but also mutational ITH and loss of expression, which together might play a role in tumorigenesis of GC and CRC with MSI-H by inhibiting tumor suppressor functions of WISP3. Our data also suggest that mutation analysis in multiregions is needed for a proper evaluation of mutation status in GC and CRC with MSI-H.

A comparative study of clinicopathological significance, FGFBP1, and WISP-2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder.

BACKGROUND: The differences in clinical, pathological, and biological characteristics between adenocarcinoma (AC) and squamous cell/adenosquamous carcinoma (SC/ASC) of gallbladder cancer have not been well documented. This study is to compare the clinicopathological characteristics and FGFBP1 and WISP-2 expression between AC and SC/ASC patients. METHODS: We examined FGFBP1 and WISP-2 expression in 46 SC/ASC and 80 AC samples using immunohistochemistry and analyzed their correlations with clinicopathological characteristics. RESULTS: SC/ASCs occur more frequently in older patients and often correspond to larger tumor masses than ACs. Positive FGFBP1 and negative WISP-2 expression were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. In addition, positive FGFBP1 and negative WISP-2 expression were significantly associated with differentiation and TMN stage in ACs. Univariate Kaplan-Meier analysis showed that either elevated FGFBP1 (p < 0.001) or lowered WISP-2 (p < 0.001) expression was closely associated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive FGFBP1 expression (p = 0.001) or negative WISP-2 expression (p = 0.035 for SC/ASC and p = 0.009 for AC) is an independent predictor of poor prognosis in both SC/ASC and AC patients. We also revealed that differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical procedure were associated with survival of both SC/ASC and AC patients. CONCLUSION: Our study suggested that the overexpression of FGFBP1 or loss of WISP-2 expression is closely related to the metastasis, invasion and poor prognosis of gallbladder cancer.

Role of oleic acid in immune system; mechanism of action; a review / Papel del ácido oleico en el sistema inmune; mecanismo de acción; revisión científica

Introduction: Although n-3 polyunsaturated fatty acids have been widely described as anti-inflammatory fats, little is known about the role of oleic acid in immune system. Aim: The aim of the present review is to join all the reports available in order to analyze where exactly the knowledge concerning this topic is and what the causes of the controversial data could be. Methods: We searched electronic databases and bibliographies of selected articles were inspected for further reference. Results: Diets rich in oleic acid have beneficial effects in inflammatory-related diseases. In addition, a wide range of studies evaluate the effect of oleic acid in different cellular functions thus reporting a potential mechanism for the biological effect of such a fat. However, some controversial data can be found in literature, maybe related to the kind of study or even the dose of the reagent added. Conclusion: In conclusion, oleic acid could be reported as an anti-inflammatory fatty acid playing a role in the activation of different pathways of immune competent cells (AU)

Introducción: Los ácidos grasos poliinsaturados de la familia n-3 han sido ampliamente caracterizados por su potencial antiinflamatorio. Sin embargo, las evidencias relativas al papel del ácido oleico en el sistema inmune son escasas. Objetivo: El objetivo de la presente revisión bibliográfica es hacer una recopilación de todos y cada uno de los trabajos publicados a este respecto, al objeto de evaluar dónde se encuentra el conocimiento relativo a esta área y cuáles pueden ser las causas de los resultados contradictorios. Métodos: Se ha realizado una búsqueda bibliográfica a través de bases de datos electrónicas y las referencias de los artículos de interés han sido utilizadas como fuente de búsquedas más avanzadas. Resultados: Las dietas ricas en ácido oleico parecen estar asociadas con un beneficio en determinadas patologías de base inflamatoria. Además, un gran número de estudios se han centrado en evaluar el papel que juega tal ácido graso en distintas funciones celulares, argumentando posibles mecanismos que sustentarían los efectos biológicos que se atribuyen a su consumo. Sin embargo, en algunos casos se observan resultados contradictorios que quizá puedan deberse al tipo de estudio desarrollado o incluso a la dosis de ácido con la que se experimenta. Conclusión: En conclusión, el ácido oleico podría ser presentado como una grasa anti-inflamatoria dado el papel que juega en la activación de distintos mecanismos de señalización de células inmunocompetentesb (AU)