The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.

PURPOSE: Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC). Here, we investigated the relationship between EGFR mutation and clinicopathologic features. EXPERIMENTAL DESIGN: EGFR mutational status of 120 NSCLCs was determined mainly in EGFR exons 18 to 21 by direct sequence and correlated with clinicopathologic parameters. RESULTS: EGFR mutations were present in 38 cases (32%) and the majority of mutations were in-frame deletions of exon 19 (19 cases) and a missense mutation in exon 21 (18 cases). EGFR mutations were frequently associated with adenocarcinoma (P < 0.0001), never smoker (P < 0.0001), and female gender (P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation (P < 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Furthermore, gender difference was observed for the mutational location (P = 0.01) dominance of exon 19 for males and exon 21 for females. Twenty-one cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib responsiveness (P = 0.002). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage; however, the difference was not significant. CONCLUSIONS: We show that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib responsiveness in NSCLC.     

Malignant B-lymphoid cells with bone lesions express receptor activator of nuclear factor-kappaB ligand and vascular endothelial growth factor to enhance osteoclastogenesis.

PURPOSE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms. EXPERIMENTAL DESIGN AND RESULTS: Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte-derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell-derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells. CONCLUSIONS: Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.     

Natural course of keratoacanthoma and related lesions after partial biopsy: Clinical analysis of 66 lesions

There is some confusion regarding the classification of keratoacanthoma (KA) and related lesions that have crateriform architecture. We examined the clinical courses of 66 KA lesions and related lesions after a partial biopsy to clarify the nosological concept of KA. We histopathologically classified these lesions into five types: (i) KA at various stages (53 lesions); (ii) KA‐like squamous cell carcinoma (SCC) (3 lesions); (iii) KA with malignant transformation (3 lesions); (iv) infundibular SCC (5 lesions); and (v) crateriform SCC arising from solar keratosis (2 lesions). We analyzed the clinical course in each group. The regression rate of KA was 98.1% and that of KA‐like SCC/KA with malignant transformation was 33.3%. No regression was observed in either infundibular SCC or crateriform SCC arising from solar keratosis. Thus, KA is a distinct entity that should be distinguished from other types of SCC with crateriform architecture based on the high frequency of regression. The regression rate of 33.3% in KA‐like SCC/KA with malignant transformation indicated that KA lesions with an SCC component still have the potential for regression. However, this result also indicated that KA is biologically unstable, and some KA tend to evolve into conventional SCC with a gradual loss of the capacity for the spontaneous regression. Infundibular SCC and crateriform SCC arising from solar keratosis are fundamentally different from KA, not only according to the histopathological findings but also based on the biological properties.     

Periodontal disease and pneumonia mortality in haemodialysis patients: A 7‐year cohort study

Aim

To evaluate the association between periodontal disease and pneumonia mortality in haemodialysis patients.

Materials and Methods

This prospective cohort study included 211 patients (mean age, 64.4 years) undergoing haemodialysis at a single medical centre. The patients underwent a baseline clinical dental examination in 2008 and were then followed up until July 2015. Periodontal disease was defined as the presence of clinical attachment loss of ≥4 mm in ≥30% of the probed sites. The primary endpoint, that is death from pneumonia, was determined by reviewing death certificates and was analysed using the competing‐risks regression model.

Results

At baseline, 92 patients (43.6%) had periodontal disease. The median follow‐up period was 84 months (interquartile range, 36–86 months). Of the 68 deaths that occurred, 21 were from pneumonia. The multivariable competing‐risks regression model showed that periodontal disease was significantly associated with death from pneumonia (adjusted subhazard ratio, 3.49; 95% confidence interval, 1.14–10.64), after adjusting for other baseline health characteristics.

Conclusions

The results of this study suggest that periodontal disease is independently associated with pneumonia mortality in haemodialysis patients. Future studies evaluating the potential effect of oral interventions for periodontal health improvement on pneumonia in haemodialysis patients would be of great interest.