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IntroductionPrognostic evaluation of bronchioloalveolar carcinoma (BAC) from a homogenous population of Caucasian patients.MethodsRetrospective analysis of resected BAC reclassified according to the 2004 World Health Organization classification of lung tumors. Analyzed variables are clinicoradiologic presentation, histologic subtypes, stage, epidermal growth factor receptor (EGFR) and HER2/neu immunohistochemical expression, EGFR exons 18, 19, and 21 mutations, K-RAS exon 2 mutation. Univariate and multivariate analyses of survival were performed.ResultsOf 40 patients analyzed, EGFR and HER2/neu expression were detected in 72% and 20%, respectively. HER2/neu expression significantly characterized mucinous BAC (46% versus 7%; p = 0.014). EGFR mutations were identified in 17% (30% in nonmucinous BAC and none in mucinous BAC; p = 0.083). K-RAS mutations were found in 42.5% (92% in mucinous BAC versus 18% in other types; p < 0.0001). Early stages (IA+IB) nonmucinous BAC had excellent prognosis: 5 years overall survival of 91% (100% for stage IA). Sixty six percent (4 of 6) of patients with multifocal disease died (two mucinous BAC and one nonmucinous BAC with recurrent disease). Seventy one percent (5 of 7) of patients with pneumonic-like tumor (all mucinous BAC) died of recurrent/progressive disease. Stage (p = 0.004) and histologic classifications (p = 0.035) resulted as independent prognostic factors at multivariate analysis.ConclusionsEarly stage nonmucinous BAC has excellent prognosis, whereas mucinous BAC presents a poor prognosis. Locally advanced nonmucinous BAC has a poor prognosis: the diagnosis of nonmucinous BAC in large tumors should be interpreted with caution given the possible presence of invasive areas in incompletely sampled tumor. Coexpression of EGFR and HER2/neu in mucinous BAC could be considered for future trials on target therapies even in Caucasian population.

Double strand RNA (dsRNA) species were previously thought to be a ‘junk DNA’ equivalent are related to endogenous retroviral elements (ERV) inserted into the human genome. Genomic integration sites and blocking of these processes have been well documented in HIV and Hepatitis C related diseases. Viral integration into human genome has been shown in a range of solid tumors, but mechanisms less understood. The detection of dsRNA in the research setting has been largely limited to cell line models and controlled transfections. To better characterize function significance of ERV and interactions at the cellular level, we outline efforts to detect and quantify such viral genomic elements with a focus on archival clinical samples in the commonly stored paraffin block. Tissue blocks issues with clinical and biochemical documented viral infection and associated viral cytopathic changes were selected from the Department of Pathology and Biorepository and standard 4 micron sections were prepared. Two (2) commercially available antibodies raised to dsRNA fragments (J2 and K1 antibodies) were directly compared by chromogenic and immunofluorescent methods. In addition, downstream biomarkers as identified by literature searches include RIG-1 and IRF 7 as moderate probable success and MDA-5 and STAT 1 as higher level success. Correlative analysis of downstream pathway markers with labeling results of dsRNA antibodies suffers from lack of sensitive measures of dsRNA fragments as opposed to the downstream cellular pathway markers. This lack of concordance likely reflects the short nature of dsRNAs in decade old paraffin tissue and/or differences in abundance. Future work will focus on developing more sensitive probes or IF probe signal amplification. Prediction of distant recurrence-free survival in resectable lung adenocarcinoma