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).…”

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?

“…In general, comparative studies have highlighted an excellent overall agreement of the two methodologies with approximately 95% of samples showing similar diploid or DNA aneuploid histograms 6 . However, two studies in squamous cell carcinoma 25,27 report significant differences in the frequency of DNA aneuploidy comparing both methods.…”

“…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 …”

Biomarkers, Stem Cells and Esophageal Cancer

“…Numerous studies have reported this p53 polymorphism in several cancers such as cervical, lung, breast, and gastric cancer (Dai et al, 2009;Dumont et al, 2003;Zhou et al, 2007), but its association with esophagus cancer remains elusive. Several specific molecular alterations play crucial roles in esophagus cancer, with tumor cell aneuploidy and p53 mutations being major hallmarks of both ESCC and EA (Blant et al, 2001;Fang et al, 2004;Jiang et al, 2010;Kuwano et al, 2005;Minu et al, 1994;Montesano et al, 1996;Souza, 2010;Whibley et al, 2009;Yu et al, 2007). Levine et al, 1991 considered that alteration or inactivation of p53 by mutations or interaction with oncogene products of DNA tumor viruses can lead to cancer.…”

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?

“…In general, comparative studies have highlighted an excellent overall agreement of the two methodologies with approximately 95% of samples showing similar diploid or DNA aneuploid histograms 6 . However, two studies in squamous cell carcinoma 25,27 report significant differences in the frequency of DNA aneuploidy comparing both methods.…”

“…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 …”

Biomarkers, Stem Cells and Esophageal Cancer

“…Numerous studies have reported this p53 polymorphism in several cancers such as cervical, lung, breast, and gastric cancer (Dai et al, 2009;Dumont et al, 2003;Zhou et al, 2007), but its association with esophagus cancer remains elusive. Several specific molecular alterations play crucial roles in esophagus cancer, with tumor cell aneuploidy and p53 mutations being major hallmarks of both ESCC and EA (Blant et al, 2001;Fang et al, 2004;Jiang et al, 2010;Kuwano et al, 2005;Minu et al, 1994;Montesano et al, 1996;Souza, 2010;Whibley et al, 2009;Yu et al, 2007). Levine et al, 1991 considered that alteration or inactivation of p53 by mutations or interaction with oncogene products of DNA tumor viruses can lead to cancer.…”

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?

“…In general, comparative studies have highlighted an excellent overall agreement of the two methodologies with approximately 95% of samples showing similar diploid or DNA aneuploid histograms 6 . However, two studies in squamous cell carcinoma 25,27 report significant differences in the frequency of DNA aneuploidy comparing both methods.…”

“…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 …”

Biomarkers, Stem Cells and Esophageal Cancer

“…Numerous studies have reported this p53 polymorphism in several cancers such as cervical, lung, breast, and gastric cancer (Dai et al, 2009;Dumont et al, 2003;Zhou et al, 2007), but its association with esophagus cancer remains elusive. Several specific molecular alterations play crucial roles in esophagus cancer, with tumor cell aneuploidy and p53 mutations being major hallmarks of both ESCC and EA (Blant et al, 2001;Fang et al, 2004;Jiang et al, 2010;Kuwano et al, 2005;Minu et al, 1994;Montesano et al, 1996;Souza, 2010;Whibley et al, 2009;Yu et al, 2007). Levine et al, 1991 considered that alteration or inactivation of p53 by mutations or interaction with oncogene products of DNA tumor viruses can lead to cancer.…”