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Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival.

Belien JA, Buffart TE, Gill AJ, Broeckaert MA, Quirke P, Meijer GA, Grabsch HI - Br. J. Cancer (2009)

Bottom Line: Results obtained from both methods were concordant in 183 (82.8%) cases (kappa=0.48).For FCM-DNA data, this difference did not reach statistical significance.The multivariate Cox model showed that ICM-DNA ploidy status predicted patient survival independently of tumour-node-metastasis status.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. jam.belien@vumc.nl

ABSTRACT

Background: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables. The aim of our study was to compare the DNA ploidy status measured using FCM-DNA and ICM-DNA in gastric cancer and to evaluate its association with clinicopathological variables.

Methods: Cell nuclei were isolated from 221 formalin-fixed, paraffin-embedded gastric cancer samples. DNA ploidy was assessed using FCM-DNA and ICM-DNA.

Results: A total of 178 (80.5%) gastric cancer samples were classified as DNA aneuploid using FCM-DNA, compared with 172 (77.8%) gastric cancer samples when using ICM-DNA. Results obtained from both methods were concordant in 183 (82.8%) cases (kappa=0.48). Patients with ICM-DNA diploid gastric cancer survived significantly longer than those with ICM-DNA aneuploid gastric cancer (log rank 10.1, P=0.001). For FCM-DNA data, this difference did not reach statistical significance. The multivariate Cox model showed that ICM-DNA ploidy status predicted patient survival independently of tumour-node-metastasis status.

Conclusion: ICM-DNA ploidy status is an independent predictor of survival in gastric cancer patients and may therefore be a more clinically relevant read out of gross genomic damage than FCM-DNA.

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Related in: MedlinePlus

Overall survival related Kaplan–Meier survival curves of patients stratified by DNA ploidy status ICM-DNA diploid+tetraploid (n=61) and ICM-DNA aneuploid (n=160) gastric cancers taking into account 9c exceeding rate. Log rank: 16.9, P<0.001, Hazard ratio: 2.8 (95% confidence interval: 1.7–4.7).
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fig1: Overall survival related Kaplan–Meier survival curves of patients stratified by DNA ploidy status ICM-DNA diploid+tetraploid (n=61) and ICM-DNA aneuploid (n=160) gastric cancers taking into account 9c exceeding rate. Log rank: 16.9, P<0.001, Hazard ratio: 2.8 (95% confidence interval: 1.7–4.7).

Mentions: A DNA diploid or DNA tetraploid ICM-DNA histogram, which showed a 9c ER>0, was reclassified as DNA aneuploid, (see the ‘Materials and Methods' section: category definition D). None of the ICM-DNA diploid but 5 of the 17 (29%) ICM-DNA tetraploid gastric cancers had nuclei with 9c ER>0. These five ICM-DNA tetraploid gastric cancers were therefore reclassified as ICM-DNA aneuploid. On the basis of category definition D (Table 2D), 61 (28%) patients with a DNA diploid or DNA tetraploid gastric cancer had a significantly longer survival compared with 160 (72%) patients with DNA aneuploid gastric cancers (Table 4 and Figure 1) (log rank of 16.8, P<0.001, with hazard ratio of 2.8 (95% confidence interval: 1.7–4.7).


Gross genomic damage measured by DNA image cytometry independently predicts gastric cancer patient survival.

Belien JA, Buffart TE, Gill AJ, Broeckaert MA, Quirke P, Meijer GA, Grabsch HI - Br. J. Cancer (2009)

Overall survival related Kaplan–Meier survival curves of patients stratified by DNA ploidy status ICM-DNA diploid+tetraploid (n=61) and ICM-DNA aneuploid (n=160) gastric cancers taking into account 9c exceeding rate. Log rank: 16.9, P<0.001, Hazard ratio: 2.8 (95% confidence interval: 1.7–4.7).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2743350&req=5

fig1: Overall survival related Kaplan–Meier survival curves of patients stratified by DNA ploidy status ICM-DNA diploid+tetraploid (n=61) and ICM-DNA aneuploid (n=160) gastric cancers taking into account 9c exceeding rate. Log rank: 16.9, P<0.001, Hazard ratio: 2.8 (95% confidence interval: 1.7–4.7).
Mentions: A DNA diploid or DNA tetraploid ICM-DNA histogram, which showed a 9c ER>0, was reclassified as DNA aneuploid, (see the ‘Materials and Methods' section: category definition D). None of the ICM-DNA diploid but 5 of the 17 (29%) ICM-DNA tetraploid gastric cancers had nuclei with 9c ER>0. These five ICM-DNA tetraploid gastric cancers were therefore reclassified as ICM-DNA aneuploid. On the basis of category definition D (Table 2D), 61 (28%) patients with a DNA diploid or DNA tetraploid gastric cancer had a significantly longer survival compared with 160 (72%) patients with DNA aneuploid gastric cancers (Table 4 and Figure 1) (log rank of 16.8, P<0.001, with hazard ratio of 2.8 (95% confidence interval: 1.7–4.7).

Bottom Line: Results obtained from both methods were concordant in 183 (82.8%) cases (kappa=0.48).For FCM-DNA data, this difference did not reach statistical significance.The multivariate Cox model showed that ICM-DNA ploidy status predicted patient survival independently of tumour-node-metastasis status.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. jam.belien@vumc.nl

ABSTRACT

Background: DNA aneuploidy reflects gross genomic changes. It can be measured by flow cytometry (FCM-DNA) or image cytometry (ICM-DNA). In gastric cancer, the prevalence of DNA aneuploidy has been reported to range from 27 to 100%, with conflicting associations with clinicopathological variables. The aim of our study was to compare the DNA ploidy status measured using FCM-DNA and ICM-DNA in gastric cancer and to evaluate its association with clinicopathological variables.

Methods: Cell nuclei were isolated from 221 formalin-fixed, paraffin-embedded gastric cancer samples. DNA ploidy was assessed using FCM-DNA and ICM-DNA.

Results: A total of 178 (80.5%) gastric cancer samples were classified as DNA aneuploid using FCM-DNA, compared with 172 (77.8%) gastric cancer samples when using ICM-DNA. Results obtained from both methods were concordant in 183 (82.8%) cases (kappa=0.48). Patients with ICM-DNA diploid gastric cancer survived significantly longer than those with ICM-DNA aneuploid gastric cancer (log rank 10.1, P=0.001). For FCM-DNA data, this difference did not reach statistical significance. The multivariate Cox model showed that ICM-DNA ploidy status predicted patient survival independently of tumour-node-metastasis status.

Conclusion: ICM-DNA ploidy status is an independent predictor of survival in gastric cancer patients and may therefore be a more clinically relevant read out of gross genomic damage than FCM-DNA.

Show MeSH
Related in: MedlinePlus