Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways

Abstract

Lung cancer is one of the most common cancers in the world with a high mortality rate. We analyzed 45 surgical samples of the adenocarcinoma, 13 with lymph node metastasis. APC, BCL2, chromogranin A, CK 5/6/18 (LP34), CK20, CK7, cyclin D1, EGFR, ERCC1, HER2, Ki67, LRP, MRP, P53, RB and TTF1 expressions were evaluated by immunohistochemistry (IHC).Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma.Acinar, micropapillary and BA/lepidic adenocarcinoma patterns were the most similar patterns and papillary was the most different pattern followed by solid pattern, according to expression of these markers. Different adenocarcinoma patterns are engaged with different molecular pathways for carcinogenesis, based on the differences of expression. Acinar, BA/lepidic and micropapillary showed higher TTF1 expression (type TRU), and papillary and solid patterns revealed less TTF1 expression, exhibiting a non-TRU/bronchial phenotype. Solid pattern revealed lower HER2 and higher EGFR and ERCC1 (this compared to papillary) expression; papillary higher HER2 and lower ERCC1 expressions; micropapillary higher RB expression; and acinar lower ERCC1 and higher EGFR expressions. Ciclin D1 seems to have more importance in acinar and BA/lepidic patterns than in micropapillary. ERCC1 protein expression in micropapillary, solid and BA/lepidic patterns may indicate DNA repair activation. Inhibition of apoptosis could be explained by BCL2 overexpression, present in all adenocarcinoma patterns. MRP-1 and LRP were overexpressed in all patterns, which may have implications for drug resistance.Further studies are needed to interpret these data regarding to therapy response in advanced staged bronchial-pulmonary carcinomas.

Heterogeneity in Lung Cancer

“…These different patters may reflect not only cellular type/ differentiation but molecular differences that could explain cellular organization and even biological behaviour, as well as prognostic and therapeutic differences in between patterns. Our research group has been addressing lung carcinomas considering histological patterns, especially in adenocarcinomas but also exploring adenosquamous and pleomorphic carcinomas [18]. For instance, we proved the relevance of pattern classification demonstrating that adenocarcinomas are molecularly different from normal adjacent tissue, and that acinar and BA/lepidic patterns are the most alike and papillary patterns the most different [18].…”

“…For instance, we proved the relevance of pattern classification demonstrating that adenocarcinomas are molecularly different from normal adjacent tissue, and that acinar and BA/lepidic patterns are the most alike and papillary patterns the most different [18]. Cluster analysis revealed three clusters: papillary, solid, and a group composed of acinar, BA/ lepidic and micropapillary patterns [18]. Papillary and solid patterns revealed lower TTF1 expression (identical to normal tissue), exhibiting a non-TRU/bronchial phenotype [18].…”

“…Cluster analysis revealed three clusters: papillary, solid, and a group composed of acinar, BA/ lepidic and micropapillary patterns [18]. Papillary and solid patterns revealed lower TTF1 expression (identical to normal tissue), exhibiting a non-TRU/bronchial phenotype [18]. Acinar, BA/lepidic and micropapillary patterns showed higher TTF1 expression corresponding to TRU origin [18].…”

“…Our research group has been addressing lung carcinomas considering histological patterns, especially in adenocarcinomas but also exploring adenosquamous and pleomorphic carcinomas [18]. For instance, we proved the relevance of pattern classification demonstrating that adenocarcinomas are molecularly different from normal adjacent tissue, and that acinar and BA/lepidic patterns are the most alike and papillary patterns the most different [18]. Cluster analysis revealed three clusters: papillary, solid, and a group composed of acinar, BA/ lepidic and micropapillary patterns [18].…”

Prenatal and Postnatal Management of Congenital Pulmonary Airway Malformation

“…2 Genes implicated in CPAM, PPB and BAC [14,30,31,32,33,34,35,127,137,138,139,140,141,142,143]. TTF1 = Thyroid transcription factor 1; PDGF-B = platelet-derived growth factor B; FABP-7 = fatty acid-binding protein 7; GDNF = glial cell-derived neurotrophic factor; Shh = sonic hedgehog; FGFR2b = FGF receptor-2b; FHIT = fragile histidine triad; Rb = retinoblastoma protein; EGFR = epidermal growth factor receptor. …”