Intestinal metaplasia identifies Barrett's esophagus (BE) and is associated with an increased risk for esophageal adenocarcinoma. Dysplasia occurs as an intermediate step. However, progression from metaplasia to neoplasia without the demonstration of dysplasia has been described. The role of dual‐parameter flow cytometry (FC) as a predictor of neoplastic risk in dysplasia‐free cases was evaluated. DNA/protein FC and histology were performed on 362 samples from 30 dysplasia‐free BE patients, followed up since 1985 once every 1–2 years. Nine cases were aneuploid, five of which (group IV) were frankly aneuploid; in the other four cases (group III), aneuploidy was detectable by dual‐parameter analysis only. Twenty‐one patients were diploid. Twelve (group II) also had an abnormally high G1‐phase protein content compared to group I (nine patients), which were diploid with a low‐moderate protein content. In three patients of group IV an adenocarcinoma in situ was diagnosed, after 5, 6, and 10 years, respectively. In two patients of group III, a low‐ and a high‐grade dysplasia were observed at 3 and 6 years follow‐up, respectively. One patient of group I first acquired a high protein content, then an aneuploid DNA content, and then progressed to adenocarcinoma (12 years). None of the still diploid patients (17 cases) have progressed to dysplasia or cancer compared with 6 of 13 presently aneuploid patients (P < 0.01). In conclusion, DNA/protein FC is a marker of increased malignant potential and thus may be used to detect patients at higher risk in dysplasia‐free BE and assist in understanding the various stages of malignant transformation in long‐term follow‐up studies. Cytometry (Comm. Clin. Cytometry) 34:257–263, 1998.  © 1998 Wiley‐Liss, Inc.

The present study was performed to improve early lung cancer diagnosis in bronchial washing fluid, thereby increasing the diagnostic sensitivity of bronchoscopy by means of high-resolution flow cytometry (FC). We combined dual-parameter DNA/protein FC and conventional cytology in bronchial washing fluid samples from 112 patients with neoplastic and non-neoplastic lung diseases and found 43% of histologically confirmed tumor cases to be cytologically positive; 63% of the tumor samples were aneuploid, 52% of the aneuploid cases were cytologically positive and 48% were negative. In the negative cases, FC was an independent diagnostic factor. In 32% of the cases, FC also failed to detect abnormalities. However, the combination of both techniques increased the sensitivity in detecting neoplastic cells to 73%. Furthermore, simultaneous DNA/protein analysis allowed the recognition of aneuploid cell lines not detectable by single DNA measurement. Identification of aneuploid subpopulations by dual-parameter analysis in cytologically negative one-parameter FC "diploid" samples assumes an important diagnostic value. Dual-parameter DNA/protein FC is a valuable technique that increases the diagnostic yield of bronchoscopy with no risk for the patient and a low additional cost.

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