Transition from squamous cell carcinoma to adenocarcinoma in adenosquamouscarcinoma of the lung

The heterogeneity of tumor cells is frequently observed in lung cancer, but the clonality of these cells has not yet been established. The distinct co mponents of 12 lung adenosquamous carcinomas mere com pared by genetic alte rations of p53 and K-ras, chromosomal abnormalities at 9p21 and 9q31-32, an d immunohistochemical reactions. The immunoreactivity of p53 was consistent in both adenocarcinomatous and squamous cell carcinomatous components as w ell as in the transitional areas, retaining the morphological characteristi cs of the distinct components. The same p53 mutation was found in both comp onents of each tumor with p53 overexpression, No K-ras mutations were detec ted in any of the tumors examined. Three of the four tumors with chromosoma l abnormalities detected, one at 9p21 and two at 9q31-32, had coincident ab normalities between the distinct components, whereas one tumor deleted homo zygously at 9p21 (D9S259) in the adenocarcinomatous component with loss of heterozygosity in the other component. The expression of squamous cell carc inoma-related antigen in adenocarcinomatous components was significantly hi gher than that of lung adenocarcinomas (57 +/- 5.8% vs. 1.0 +/- 0.5%, P < 0 .0001), whereas Mucin 1 expression is less in these components (9.0 +/- 4.9 % vs. 55 +/- 8.2%, P = 0.003), These results suggest monoclonal transition from squamous cell, carcinoma to adenocarcinoma in lung adenosquamous carci noma.