Prognostic significance of DNA ploidy in adenocarcinoma of the pancreas. A flow cytometric study of paraffin-embedded specimens

Abstract

Background. The prognostic significance of tumor DNA ploidy in patients with cancer of the pancreas has not been defined because conflicting results have been reported. Methods. DNA content was measured in 56 ductal adenocarcinomas of the pancreas. DNA ploidy status was evaluated by flow cytometry in nuclei isolated from paraffin‐embedded tumor tissues. Results. An abnormal DNA stemline was observed in 27 (48%) patients. The percentage of aneuploid tumors was significantly increased in tumors classified as Stage III/IV (53%) compared with those classified as Stage I (22%). A borderline significant association existed between DNA ploidy and radicality of surgery (P = 0.08). The median survival of patients with diploid carcinomas was 6.9 months (standard error, ±0.9) in comparison to 4.5 ± 1.2 months for patients with aneuploid tumors (P = 0.013 by generalized Wilcoxon test; P = 0.023 by generalized Savage test). Although a selection bias cannot be excluded, survival of patients with a radical resection was longer than that of patients with a nonradical resection (P = 0.0008 and P = 0.0085, respectively). In addition, presence of distant metastasis (P = 0.0006 [Wilcoxon test] and P = 0.033 [Savage test]) could be identified as a prognostic factor. In a Cox regression model, results of surgery and DNA ploidy were independent prognostic variables. Conclusions. Because DNA ploidy has a significant impact on prognosis in pancreatic cancer, it should be used as a variable for stratified randomization of patients in therapeutic trials.

Evaluation of DNA ploidy in relation with established prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis

“…In multivariate analysis, the only factors associated with survival were radicality of surgery and DNA ploidy. The authors concluded that DNA ploidy adds valuable information which is distinct from other clinico-pathological variables [34]. Similar results have been reported by others [35-39].…”

“…Berczi et al also concluded using flow cytometry analysis that DNA ploidy status had no significant effect on survival of patients with carcinoma of the pancreatic head region [43]. To some extend, disparate results in DNA ploidy studies have been ascribed to the differing techniques employed, and the heterogeneity in the nuclear DNA content in pancreatic tumor cells, hence image cytometry has generally been considered superior to flow cytometry as only tumor cells are used for DNA measurement [34]. Subsequently, the clinical utility of DNA ploidy has been limited and its role in staging and treatment is still under investigation [27].…”

Factors Influencing Survival in Stage IV Colorectal Cancer: The Influence of DNA Ploidy

“…The majority of the reported studies have employed flow cytometric derived DNA ploidy, and the American Society of Clinical Oncology Tumour Markers Expert Panel has reviewed fifteen articles (encompassing 14 independent series) evaluating the prognostic role of flow cytometric derived ploidy in CRC to support its recommendation regarding the unsuitability of this marker as a prognostic determinant due to largely controversial results [24]. To some extent, disparate results in DNA ploidy studies have been ascribed to the differing techniques employed (flow cytometry versus DNA image cytometry) and the heterogeneity in the nuclear DNA content in colonic tumour cells; hence, image cytometry has generally been considered superior to flow cytometry as only tumor cells are used for DNA measurement [25]. Despite its technical advantages, image cytometry has only been applied to a limited number of studies which were particularly aimed to identify patients with stage II disease with high risk of recurrence following curative resection and assess the survival benefit of adjuvant chemotherapy.…”

Molecular biological observations in some rare neoplasms: DNA ploidy and cell cycle data in liposarcoma and malignant fibrous histiocytoma

“…A cell suspension was produced by continuous shaking and incubation of the specimens overnight with a trypsin solution (0.25%) (DIFCO, Detroit, Mich., USA) containing citrate buffer (trisodiumcitrate 3.0 mM, Nonidet P40 0.1%, (Boehringer Mannheim, Germany), sperminetetrachloride 1.5 mM and TRIS 0.5 mM (USB, Cleveland, Ohio, USA), pH 7.6, 37°C [16,17]. After incubation, the suspension was vortexed, filtered twice through a 70-mm nylon mesh, and centrifuged (1200 rpm; 296 g, 8 min).…”