Bronchioloalveolar invasion in non-small cell lung cancer is associated with expression of transforming growth factor-beta1

Background: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with fibrous stromal invasion are newly introduced subtypes of small lung adenocarcinoma. AIS is a small localized adenocarcinoma in which growth is restricted to neoplastic cells along preexisting alveolar structures without fibrous stromal invasion. In MIA, by contrast, tumor cells have infiltrated the myofibroblastic stroma. Transforming growth factor (TGF)-beta is known to be produced by progressor tumors, and excessive TGF-beta contributes to a pathological excess of tissue fibrosis. TGF-beta1 is the most abundant isoform, and its expression is a key event fostering tumor invasion and metastasis. We therefore analyzed the relationship between TGF-beta1 expression and clinicopathological microinvasion in patients with small lung adenocarcinoma. Methods: The study participants were 45 patients who underwent curative surgery for AIS and MIA 3 cm or less in size. Those tumors were assessed based on immunohistochemical staining using anti-TGF-beta1 antibody. The TGF-beta1 status was assessed immunohistochemically using the Allred 8-unit system. Results: The rates of TGF-beta1 positivity in the AIS and MIA groups were 27.3% and 65.2%, respectively (P <0.05). The median of Allred score was 0.5 (range 0--5) in the AIS group and 3.0 (range 0--6) in the MIA group (P = 0.0017). Conclusions: We suggest that TGF-beta1 expression is likely to be significantly stronger in patients with MIA than in those with AIS, and the increased expression may be associated with minimal invasion and infiltration of the myofibroblastic stroma.

via World Journal of Surgical Oncology