title: Immunohistopathological re-evaluation of adenocarcinoma of the lung with mixed subtypes using a tissue microarray technique and hierarchical clustering analysis.
abstract: To re-evaluate adenocarcinoma, mixed subtypes (ADMIX) of the lung, a total of 201 cases were classified into three main subgroups according to the most differentiated histological growth pattern; namely bronchioloalveolar carcinoma (BAC)-mixed, which was the most predominant (73.1%), papillary (PAP)-mixed (21.9%), and acinar-mixed (5%). The PAP-mixed was significantly male predominant and had more progressed clinicopathological features. A significant cytological difference was observed among the three subgroups. A tissue microarray was constructed and immunohistochemistry was undertaken using 15 biomarkers. Hierarchical clustering analysis was separately applied to the immunohistochemical results of ADMIX and ADMIX subgroups, and it was found that most acinar-mixed cases were placed in a separate cluster, while the BAC-mixed and PAP-mixed failed to form significant independent clusters. The antibody clustering profile for the acinar-mixed was clearly different from that for the BAC-mixed or PAP-mixed, but the PAP-mixed shared a dendrogram profile with the other two subgroups. Statistically, approximately half of the 15 biomarkers were significant for differentiating between ADMIX subgroups and between different histological growth patterns. In conclusion, ADMIX can be classified into three histopathological subgroups according to the most differentiated growth pattern, of which a PAP growth pattern might indicate more aggressive behavior than that of a BAC growth pattern.
authors.affiliation: Department of Tumor Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Gehan
authors.initials: G
authors.lastname: Gamal
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sano
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakurai
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawashima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sugano
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000145:classification* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor