DNA Ploidy and Markovian Analysis of Neoplastic Progression in Experimental Pancreatic Cancer

Abstract

S U M M A R YComputer-assisted analysis of DNA ploidy and nuclear morphology were used to elucidate changes in the cell nucleus that occur during the development of experimental pancreatic cancer. Ductal pancreatic adenocarcinoma was induced in 49 Syrian hamsters by SC injection of N -nitrosobis (2-oxopropyl) amine; twenty hamsters served as controls. Groups of animals were sacrificed every 4 weeks for 20 weeks and adjacent sections of pancreatic tissue were H&E and Feulgen-stained for light microscopy and computer assisted cytometry. Pancreatic ductal cells were classified as normal, atypical, or malignant; tissue inflammation (pancreatitis) was also noted when present. DNA ploidy and nuclear morphology evaluation (Markovian analysis) identified an atypical cell stage clearly distinguishable from either normal or malignant cells; pancreatitis preceded this atypia. The DNA ploidy histogram of these atypical cells revealed a major diploid peak and a minor aneuploid peak. The receiver operator characteristic curve areas for a logistic regression model of normal vs atypical cells was 0.94 and for atypical vs malignant was 0.98, numbers indicative of near-perfect discrimination among these three cell types. The ability to identify an atypical cell population should be useful in establishing the role of these cells in the progression of human pancreatic adenocarcinoma.

Transgenic expression of CCK2 receptors sensitizes murine pancreatic acinar cells to carcinogen‐induced preneoplastic lesions formation

“…22 We thus analyzed the morphology of azaserine-treated pancreas from transgenic and control mice by hematoxylin/eosin (H&E) staining of paraffin-embedded sections at 2, 4 and 6 months after the last injection of carcinogen. There was evidence of minimal lymphocyte infiltration in pancreas of both control and ElasCCK2 treated mice (Fig.…”

Nuclear Ploidy as an Indicator of Malignancy of Intraductal Pancreatic Papillary Mucinous Tumors

“…High levels of nuclear ploidy were detected in ductal adenocarcinoma cells in patients [4,13] and in animals with experimental pancreatic cancer [12]. Unfortunately, only few studies were focused on the analysis of DNA content in pancreatic IPMC.…”

Expression of prohibitin 3? untranslated region suppressor RNA alters morphology and inhibits motility of breast cancer cells

“…Approximately 300 nuclei of Feulgenstained cells (from 3-4 individual animals per group) were evaluated for a specific array of morphometric characteristics including 26 size, shape and texture features using a Cell Measurement Program (Cell Analysis Systems, Lombard, IL) as described previously (Postier et al 2003). The data were analyzed by first evaluating the Markovian texture features for relevance using backwards stepwise logistic regression analysis (SAS System software version 6.10).…”

“…The data were analyzed by first evaluating the Markovian texture features for relevance using backwards stepwise logistic regression analysis (SAS System software version 6.10). Secondly, AccuRoc software (Accumetric, Montreal, Canada) was used to evaluate the resulting models for discriminatory power by receiver operator characteristic (ROC) curves for continuous variables as previously described (Veltri et al 1994, Postier et al 2003.…”

“…Logistic regression with model building by backward stepwise elimination (Postier et al 2003) was used to determine a combination of a minimum of 18 Markovian texture features that best discriminated between UTR/C and EV cells. The discriminatory power of the models was evaluated by ROC curves for continuous variables.…”