Loss of alveolar basement membrane type IV collagen α3, α4, and α5 chains in bronchioloalveolar carcinoma of the lung

Type IV collagen, the major component of basement membrane (BM), is composed of six genetically distinct α(IV) chains. This study investigated for the first time the expression of these six α(IV) chains immunohistochemically, using α(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 α1(IV)/α2(IV) chains and α3(IV)/α4(IV)/α5(IV) chains. In non-collapsed areas of BAC, alveolar BM was composed of linear α1(IV)/α2(IV) chains and discontinuous α3(IV)/α4(IV)/α5(IV) chains. In collapsed areas of BAC, alveolar BM was composed of linear and thick α1(IV)/α2(IV) chains only, because of the complete loss of α3(IV)/α4(IV)/α5(IV) chains. In invasive areas of adenocarcinoma with bronchioloalveolar features, α1(IV)/α2(IV) chains around the cancer cell nests were disrupted, in addition to the complete loss of α3(IV)/α4(IV)/α5(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 α1(IV)/α2(IV)/α3(IV)/α4(IV)/α5(IV) chains, to the incomplete type, composed of only α1(IV)/α2(IV) chains, before the disruption of α1(IV)/α2(IV) chains. These findings may help to clarify the molecular mechanisms of cancer invasion. Copyright © 2001 John Wiley & Sons, Ltd.