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Background: Predominant histologic subtypes have been reported as predictors of survival of patients with pulmonary adenocarcinoma., Aims: To evaluate the predictive value of histologic classification in resected lung adenocarcinoma using the classification systems proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and World Health Organization (2015)., Study Design: Cross-sectional study., Methods: The histologic classification of a large cohort of 491 patients with resected lung adenocarcinoma (stages I-III) was retrospectively analyzed. The tumors were classified according to their predominant component (lepidic, acinar, papillary, solid, micropapillary, and mucinous), and their predictive values were assessed for clinicopathologic characteristics and overall survival., Results: The patient cohort comprised 158 (32.2%) patients with solid predominant, 150 (30.5%) with acinar predominant, 80 (16.3%) with papillary predominant, 75 (15.3%) with lepidic predominant, 22 (4.5%) with mucinous, and 5 (1.0%) with micropapillary subtype, and 1 (0.2%) with adenocarcinoma in situ . Overall 5-year survival of 491 patients was found to be 51.8%. Patients with lepidic, acinar, and mucinous adenocarcinoma had 70.9%, 59.0%, and 66.6% 5-year survival, respectively, and there was no statistically significant difference between them. Whereas patients with solid, papillary, and micropapillary predominant adenocarcinoma had 41.0%, 40.5%, and 0.0% 5-year survival, respectively. Compared to other histologic subtypes, patients with solid and papillary predominant adenocarcinoma had significantly lower survival than those with lepidic (p<0.001, p=0.002), acinar (p<0.001, p=0.008), and mucinous (p=0.048, p=0.048) subtypes, respectively. The survival difference between patients with solid subtype and those with papillary subtype was not statistically significant (p=0.67)., Conclusion: Solid and papillary histologic subtypes are poor prognostic factors in resected invasive lung adenocarcinoma.

Background: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date., Aims: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition., Study Design: Animal experimentation., Methods: Twenty-six Wistar rats were randomized into four groups: control (CTRL), radiation (RT), VA plus radiation (VA+RT), and DX plus radiation (DX+RT). Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and matrix metal-loproteinases (MMP-2 and MMP 9) were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay., Results: VA decreased the levels of TNF-α and IL-1β proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis., Conclusion: Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in early radiation and these effects are independent from MMP inhibition., Competing Interests: No conflict of interest was declared by the authors.