Comparison of ACINUS, caspase-3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis.

Full Abstract

BACKGROUND: The balance between apoptotic and proliferative processes determines the enlargement of a tumor. Accurate measurement of apoptotic and proliferative rates from diagnostic prostate biopsies would allow calculation of tumor growth rates in a population-based prostate cancer (CaP) study. Automated image analysis may be used if proliferation and apoptotic biomarkers provide clearly resolved immunostained images. METHODS: Clinical CaP aggressiveness was assigned as low, intermediate or high using clinical criteria for 46 research subjects with newly diagnosed CaP. Diagnostic biopsy sections from the research subjects were dual-labeled for proliferation biomarker, Ki-67 and apoptotic biomarker, apoptotic chromatin condensation inducer in the nucleus (ACINUS). Apoptotic biomarkers, caspase-3 and terminal deoxyribonucleotidyltransferase mediated dUTP-biotin nick end labeling (TUNEL) were labeled separately. Images from immunostained sections were analyzed using automated image analysis and tumor growth rates computed. Association between clinical CaP aggressiveness and tumor growth rates was explored. RESULTS: Sixteen subjects had high, 17 had intermediate, and 13 had low clinical CaP aggressiveness. Positive immunostaining was localized to the nucleus for Ki-67, ACINUS, and TUNEL. A statistically significant linear trend across clinical CaP aggressiveness categories was found when tumor growth rates were calculated using ACINUS (P = 0.046). Logistic regression and ROC plots generated showed ACINUS (AUC = 0.677, P = 0.048) and caspase-3 (AUC = 0.694, P = 0.038) to be better predictors than TUNEL (AUC = 0.669, P = 0.110). CONCLUSIONS: ACINUS met the criteria for automated image analysis and for calculation of apoptotic rate. Tumor growth rates determined using automated image analysis should be evaluated for clinical prediction of CaP aggressiveness, treatment response, recurrence, and mortality.

Author information

Author/s: Singh, Swaroop S (SS); Mehedint, Diana C (DC); Ford, O Harris (OH); Jeyaraj, D Antony (DA); Pop, Elena A (EA); Maygarden, Susan J (SJ); Ivanova, Anastasia (A); Chandrasekhar, Rameela (R); Wilding, Gregory E (GE); Mohler, James L (JL);

Affiliation: Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. swaroop.singh(-atsign-)roswellpark.org

Grants: CA016156 (Agency:NCI NIH HHS) ; CA34026 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: The Prostate (Prostate), published in United States. (Language: eng)

Reference: 2009-Nov; vol 69 (issue 15) : pp 1603-10

Dates: Created 2009/09/28; Completed 2009/10/15;

PMID: 19644955, status: MEDLINE (last retrieval date: 10/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Ki-67 Antigen - analysis
Logistic Models
Male
Nuclear Proteins - analysis
Predictive Value of Tests
Prostatic Neoplasms - metabolism; pathology
ROC Curve
Tumor Markers, Biological - analysis

Associated Chemicals: ACIN1 protein, human (0) ; Ki-67 Antigen (0) ; Nuclear Proteins (0) ; Tumor Markers, Biological (0) ; Caspase 3 (EC 3.4.22.-)

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