Histology-dependent prognostic role of pERK and p53 protein levels in early-stage non-small cell lung cancer.

Lung tumors represent a major health problem. In early stage NSCLC tumors, surgical resection is the preferred treatment, but 30-55% of patients will relapse within 5 years after surgery. Thus, the identification of prognostic biomarkers in early stage NSCLC patients, especially those which are therapeutically addressable, is crucial to enhance survival of these patients. We determined the immunohistochemistry expression of key proteins involved in tumorigenesis and oncogenic signaling, p53, EGFR, pAKT and pERK, and correlated their expression level to clinicopathological characteristics and patient outcome. We found EGFR expression is higher in the squamous cell carcinomas than in adenocarcinomas (p=0.043), and that nuclear p53 staining correlated with lower differentiated squamous tumors (p=0.034). Regarding the prognostic potential of the expression of these proteins, high pERK levels proved to be an independent prognostic factor for overall (p<0.001) and progression-free survival (p<0.001) in adenocarcinoma patients, but not in those from the squamous histology, and high p53 nuclear levels were identified as independent prognostic factor for progression-free survival (p=0.031) only in squamous cell carcinoma patients. We propose a role as early prognostic biomarkers for pERK protein levels in adenocarcinoma, and for nuclear p53 levels in squamous cell lung carcinoma. The determination of these potential biomarkers in the adequate histologic context may predict the outcome of early stage NSCLC patients, and may offer a therapeutic opportunity to enhance survival of these patients.

Prognostic Role of the FGFR4-388Arg Variant in Lung Squamous-Cell Carcinoma Patients With Lymph Node Involvement.

BACKGROUND: The identification of prognostic biomarkers for lung squamous-cell carcinoma (SCC) pathology is crucial because of its poor prognosis. A variant of the FGFR4 (fibroblast growth factor receptor 4) gene, FGFR4-388Arg, has been associated with prognosis and is linked to oncogenesis in vitro in several types of cancer. We analyzed the association of this variant with prognosis and downstream signaling alteration in lung SCC patients. METHODS: The presence of the FGFR4-388Arg variant was determined in 114 formalin-fixed, paraffin-embedded lung SCC tissue samples by DNA genotyping and was correlated with clinicopathologic data. The activation of the protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) pathways was determined by immunohistochemistry, and its association with the presence of FGFR4-388Arg was analyzed. RESULTS: We found that tumor differentiation status and adjuvant chemotherapy administration could be independent prognostic factors for overall survival (OS) in lymph node-affected patients, as expected. The progression-free survival and OS of patients with lymph node involvement (n = 41) and the FGFR4-388Arg genotype were significantly lower than those of patients lacking this variant (P = .035 and P = .042, respectively). Importantly, multivariate analysis supported the independent prognostic role of the FGFR4-388Arg genotype in OS (P = .025). Regarding downstream signaling, the FGFR4-388Arg genotype was not correlated with altered AKT signaling but was associated with increased MAPK activation in the SCC tumor samples (P = .017). CONCLUSION: The FGFR4-388Arg variant may represent a promising prognostic biomarker in SCC patients with lymph node involvement. For these patients, FGFR4 may be a potential therapeutic target.

MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs) are involved in numerous biological and pathological processes including colorectal cancer (CRC). The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). METHODS: We examined expression levels of 667 miRNAs in the training cohort and evaluated their potential association with relevant clinical endpoints. We identified a miRNA profile that was analysed by RT-qPCR in an independent cohort. For a set of selected miRNAs, bioinformatic target predictions and pathway analysis were also performed. RESULTS: Eight miRNAs (let-7 g*, miR-107, miR-299-5p, miR-337-5p, miR-370, miR-505*, miR-889 and miR-99a-3p) were significant predictors of response to chemotherapy in the training cohort. In addition, overexpression of miR-107, miR-337-5p and miR-99a-3p, and underexpression of miR-889, were also significantly associated with improved progression-free and/or overall survival. MicroRNA-107 and miR-99a-3p were further validated in an independent cohort as predictive markers for chemotherapy response. In addition, an inverse correlation was confirmed in our study population between miR-107 levels and mRNA expression of several potential target genes (CCND1, DICER1, DROSHA and NFKB1). CONCLUSIONS: MiR-107 and miR-99a-3p were validated as predictors of response to standard fluoropyrimidine-based chemotherapy in patients with mCRC.

Groove pancreatitis: MRI and pathologic findings.

OBJECTIVE: Our purpose is to describe the MRI findings with pathologic correlation, in five patients with groove pancreatitis, a specific form of chronic pancreatitis affecting the groove between the pancreatic head, the common bile duct and duodenum. MATERIALS AND METHODS: Five patients with pathologically proven (four cases) and clinical and MRI findings (follow-up) consistent with the diagnosis of groove pancreatitis (one case) were reviewed. Three patients underwent cephalic pancreatoduodenectomy (Whipple procedure) due to severe duodenal stenosis; MRI findings were correlated with the histological findings. RESULTS: In all patients a mass was seen affecting the groove between the pancreatic head and the duodenum. Precontrast images demonstrated hypointense tissue relative to pancreatic parenchyma on T1-weighted images and iso to slightly hyperintense tissue on STIR and T2-weighted images. Postcontrast dynamic Gd-DTPA images, showed peripheral mass enhancement on immediate postgadolinium images and progressive and centripetal mass enhancement on delayed images with good delineation of multiple cysts. Histologically, fibro-inflammatory tissue was demonstrated in the groove and the duodenal wall with obliterative concentric scarring of the distal common bile duct. CONCLUSIONS: MRI findings are demonstrative of the pathologic features characteristic of this entity: the fibrous tissue in the pancreaticoduodenal groove, the duodenal wall inflammation and the groove and/or duodenal wall cyst formation.

Recurrent central giant cell granuloma in the mandible: surgical treatment and dental implant restoration.

Central giant cell granuloma is an uncommon benign intraosseus lesion of jaws. Traditional treatment has been local curettage, although aggressive sub-types have a high tendency to recur. This patient report describes a recurrent central giant cell granuloma involving the body of the mandible in a 48-year-old-woman. Initial treatment of lesion consisted of curettage and peripheral ostectomy. When recurrence was detected one year later, an en bloc resection and defect regeneration with a composite bone graft of autogenous bone, xenograft, and autologous platelet-rich plasma was carried out. Adequate new bone formation was observed during follow-up of 24 months. Two dental implants were placed, and implant-supported prosthesis was constructed, providing a satisfactory dental restoration.