Evolution of DNA ploidy during squamous cell carcinogenesis in the esophagus

Abstract

Image and flow cytometry was used to study the nuclear DNA content (ploidy) during the squamous cell carcinogenesis in the esophagus. The present retrospective study comprised 26 surgical specimens of squamous cell carcinomas (SCC) in patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne, between January 1992 and December 1999. We analyzed 53 healthy tissues, 43 tumors, and six lymph node metastases. Diploid DNA histogram patterns were observed in all non-pathologic tissues analyzed, either distant or proximal to the lesion. Aneuploidy was observed in 30 (70%) of 43 lesions; 20 (62.5%) of 32 early squamous-cell carcinomas; and 10 (91%) of 11 advanced carcinomas. In patients with various tumor stages or with multicentric synchronous or metachronous tumors, DNA content was not different among different tumor stages. Four of six lymph node metastases had the same DNA content as the primary tumor. In four patients, discordance between image and flow cytometry analysis was observed for malignant lesions only. Ploidy status was not statistically associated with the differentiation of the tumor, but it was associated with the stage of tumor (P < 0.001). These findings suggest that early malignant changes in the esophagus are already associated with alteration in DNA content, and aneuploidy tends to correlate with progression to invasive SCC. This cell kinetic information could help clinicians in selecting the optimal treatment for the individual patient.

Non-random Chromosomal Aberrations in Peripheral Blood Leucocytes of Gastrointestinal Tract and Breast Cancer Patients

“…Polyploidy is an indicator of fast growing tumors. Ploidy status is associated with the advancing stage of tumor but it is not statistically associated with the differentiation of tumor (Blant et al 2001). The formation of aneuploid genome might be the initiating step in neoplastic conversion (Matzke et al 2003).…”

Is there a case for routine clinical application of ploidy measurements in gastrointestinal tumours?

“…A correlation between DNA aneuploidy and poor histological grade was reported by several authors 10–13 but this was not seen in other studies 14–20 . Similarly, several authors reported that DNA aneuploid oesophageal tumours were more often of advanced stage than diploid tumours, 10,13 , 15,21–25 but others have failed to confirm this 11,14 , 16,19 , 20 . DNA ploidy determination in oesophageal squamous cell carcinoma produced conflicting reports concerning prognosis.…”

“…Several studies established DNA aneuploidy as an independent predictor of poor survival using multivariate analysis 21,28 , 31–34 . On the other hand, one study reported that patients with diploid tumours had a poorer survival than those with DNA aneuploid tumours 14 and other authors demonstrate that DNA aneuploidy was not a useful marker in predicting patient survival at all 11,13,16–18,20,25,35,36 …”

Occurrence of multipolar mitoses and association with Aurora-A/-B kinases and p53 mutations in aneuploid esophageal carcinoma cells

“…In fact, aneuploidy is found in 50% to 70% of ESCC and is associated with poor prognosis [6,7]. In BAC, similar high rates of aneuploidy are seen for invasive carcinomas [8,9], and aneuploidy is an early event in the metaplasia-dysplasia-adenocarcinoma sequence of BAC.…”