Loss of alveolar basement membrane type IV collagen alpha3, alpha4, and alpha5 chains in bronchioloalveolar carcinoma of the lung

Abstract

Type IV collagen, the major component of basement membrane (BM), is composed of six genetically distinct alpha(IV) chains. This study investigated for the first time the expression of these six alpha(IV) chains immunohistochemically, using alpha(IV) chain-specific monoclonal antibodies, in normal lung and in small (less than 2 cm in diameter) adenocarcinoma of the lung with a bronchioloalveolar growth pattern at the periphery. Small adenocarcinomas were histopathologically classified into three subtypes: bronchioloalveolar carcinoma (BAC) without collapse, BAC with collapse, and adenocarcinoma with bronchioloalveolar features. In normal lung, alveolar BM was composed of alpha1(IV)/alpha2(IV) chains and alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In non-collapsed areas of BAC, alveolar BM was composed of linear alpha1(IV)/alpha2(IV) chains and discontinuous alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In collapsed areas of BAC, alveolar BM was composed of linear and thick alpha1(IV)/alpha2(IV) chains only, because of the complete loss of alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In invasive areas of adenocarcinoma with bronchioloalveolar features, alpha1(IV)/alpha2(IV) chains around the cancer cell nests were disrupted, in addition to the complete loss of alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In conclusion, during the process of stromal invasion of lung adenocarcinoma, type IV collagen of alveolar BM is remodelled from the complete type, composed of alpha1(IV)/alpha2(IV)/alpha3(IV)/alpha4(IV)/alpha5(IV) chains, to the incomplete type, composed of only alpha1(IV)/alpha2(IV) chains, before the disruption of alpha1(IV)/alpha2(IV) chains. These findings may help to clarify the molecular mechanisms of cancer invasion.