HDAC Inhibitors as Epigenetic Regulators

In the old age group, 177 were biopsy cases whereas 84 were excision cases. metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was SCH 54292 rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of SCH 54292 young patients demonstrates unique pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed. mutations are frequently recognized in females, nonsmokers, Asian ethnics (9, 10), and are related to a bronchioloalveolar growth pattern (11) or papillary and micropapillary features (12). Non-small cell lung cancers (NSCLC) having ALK rearrangement are associated with a more youthful age group, with non-smokers, with males, and have a signet ring cell morphology (13, 14). As explained above, predominantly females, nonsmokers and cases of adenocarcinoma histology are closely associated with young patients who have lung malignancy, and thus we hypothesized that specific molecular and pathologic features might be associated with lung adenocarcinoma arising in young patients. Despite our research, most studies regarding lung malignancy in young patients have focused on clinical characteristics, not on a thorough evaluation of pathologic features and molecular characteristics (2, 3, 5, 8). Furthermore, although a large proportion of young patients with lung adenocarcinoma offered at an advanced stage, the studies focusing on the pathologic features enrolled only surgically treated cases (15). Immunohistochemistry (IHC) is usually a widely relevant technique in pathology laboratories for the analysis of even small biopsy samples or cytologic preparations which often struggle to provide sufficient amounts or high quality samples of DNA. Furthermore, IHC preserves tissue morphology and can detect a very small number of mutation-positive malignancy cells even in the cases with overwhelming amounts of non-neoplastic cells. When using direct sequencing methods to detect mutation, small biopsy samples often do not provide enough DNA with a high enough quality to process, and mutations in tumor samples, in which the quantity of mutations in lung malignancy, which represent 85%-90% of mutations in lung malignancy; an L858R substitution mutation in exon 21 (L858R) and in-frame deletions in exon 19 (E746) (9). They showed that these antibodies are highly sensitive and specific with a sensitivity of 79%-95%, and a specificity of SCH 54292 99% for both antibodies, respectively (16, 17). Thus, an IHC assay with mutation-specific antibodies is usually a simple, quick and reliable screening method to identify mutations especially in small biopsy tissue samples of lung malignancy (16). Fluorescent in situ hybridization (FISH) is usually a standard method to detect ALK rearrangement in lung malignancy, but it is usually difficult to use FISH on all the biopsied or resected lung malignancy samples because ALK rearrangement rate in NSCLC is very low (13) and the cost of FISH is very high. Paik et al. (14) exhibited a good correlation between the results using a semi-quantitative scoring method with IHC and FISH for ALK rearrangement and reported the sensitivity and specificity at 100% and 95.8% respectively. Based on these findings, the IHC assay may be useful as a screening method to detect ALK-rearranged lung malignancy. In this study, we evaluated the clinicopathologic characteristics of lung adenocarcinoma of young patients and tested mutation status and ALK rearrangement using IHC in patients more youthful than 40 yr of age compared with those over 50 yr of age. MATERIALS AND METHODS Subjected patients This study included 1,255 consecutive patients with main lung malignancy who underwent histologic diagnosis at Inha University or college Hospital, Korea, between 1998 and 2009. Cases with a history of other known malignancies or clinically diagnosed lung SCH 54292 malignancy cases without histologic confirmation were excluded. The patients were divided into three groups according to the age at diagnosis: a young age group encompassing patients who were 40 yr aged or more youthful, an old age group encompassing patients who were older than 50 yr of age, and an intermediate age group encompassing the patients who were 41 to 50 yr aged (inclusive). A total of 52 cases were categorized as the young age group, 1,095 cases comprised the old age group and 108 cases created the intermediate age group. Because the Mctp1 patients aged between 41 and 50 yr showed common features of the other two age groups, we excluded the intermediate group around the statistical evaluations of the clinicopathologic differences between the young.