Image Cytometric DNA Analysis and Proliferating Cell Nuclear Antigen (PCNA) Expression in Transitional Cell Carcinoma of the Bladder

Ioakim-Liossi, A.; Karakitsos, Peter; Pantazopoulos, D; Aroni, Kyriaki; Athanossiadou, Pauline

doi:10.1046/j.1525-1500.1999.99048.x

Cited by 6 publications

(13 citation statements)

References 14 publications

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“…The proliferative activity of malignant tumours has been implicated as a prognostic parameter for the aggressiveness of the tumours and correlated with outcome for several human carcinomas 2,16,17 …”

Section: Discussionmentioning

confidence: 99%

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Expression of p120, Ki‐67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value

et al. 2004

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The cell proliferation markers p120, Ki-67 and proliferating cell nuclear antigen (PCNA) recognize nuclear antigens. The expression of these proteins by immunostaining methods was reported to be of value in determining the prognosis of patients with malignant diseases. In this study, we evaluated the prognostic significance of the expression of nuclear antigens p120, PCNA and Ki-67 in prostate cancer and compared the results with other prognostic factors. Imprint smear samples obtained from 70 patients immediately after radical prostatectomy for prostatic carcinoma were immunostained with monoclonal antibodies against p120, Ki-67 and PCNA. The immunostaining results were correlated with Gleason score, tumour differentiation, stage and prostatic specific antigen (PSA) levels. Our findings demonstrate that p120, Ki-67 and PCNA expression in prostatic carcinoma smears, correlated significantly with the degree of Gleason score (P < 0.001). When combining p120, Ki-67 and PCNA positivity with tumour differentiation there was a significant association among these parameters (P < 0.001). Overexpression of p120, Ki-67 and PCNA, was also associated with increased PSA serum levels (>4 ng/ml) (P < 0.001). The distribution of p120, Ki-67 and PCNA expression in prostate carcinomas was not statistically significant for Ki-67 (P = 0.69) and p120 (P = 0.22) but was significant for PCNA (P < 0.001) as far as the histological stage (T2a, T2b, T2c, T3a). P120, Ki-67 and PCNA expression had significant prognostic value for disease-free survival. Our results conclude that nuclear antigens p120, Ki-67 and PCNA appear to be additional markers in the field of prognosis of prostatic carcinoma.

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Section: Discussionmentioning

confidence: 99%

“…Many investigators have been focusing on identifying prognostic parameters that can separate the aggressive tumours from relatively indolent ones. Cell proliferation has been shown to be a significant prognostic factor in several human malignancies 1–3 …”

Section: Introductionmentioning

confidence: 99%

Expression of p120, Ki‐67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value

et al. 2004

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“…Histopathological stage and grade are conventional prognostic factors for predicting biological behavior (5).…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of static cytometry in transitional cell carcinoma of the bladder: Recurrence rate and survival in a group of patients at 10 years follow-up

Cai

Margallo²,

Nesi³

et al. 2006

Oncol Rep

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Abstract. Many studies have indicated that nuclear DNA content evaluation can be used to predict biological behavior of transitional cell carcinoma (TCC) of the bladder. Some authors also indicated that static cytometry is more useful in DNA content analysis than flow cytometry. The aim of the present study was to evaluate the prognostic significance of DNA ploidy in TCC of the bladder, performed by using static cytometry with an image analyzer, and monitoring patients at 10 years follow-up. Thirty-one consecutive patients underwent transurethral or open surgery for bladder tumors, and neoplastic tissue samples taken from each patient were imprinted on glass slides and sent for histopathological and DNA content evaluation. DNA ploidy evaluation was performed using a CAS 200 image analyzer. Nuclear DNA content evaluation was compared to patient follow-up on recurrence, progression or survival performed 10 years after surgery. Pathological evaluation demonstrated the presence of superficial TCC in 23 patients, while 8 had an invasive bladder tumor. Twenty-nine tumor samples were adequate for DNA content measurement, with 13 showing diploid DNA content and 16 with aneuploid DNA content. At 10 years follow-up, all patients with aneuploid DNA content demonstrated a lower survival time (p=0.049) and higher recurrence rate (p=0.0346). A log-rank test demonstrated that stage, grade and nuclear DNA content are the most useful prognostic parameters for predicting the biological behavior of TCC of the bladder. These results confirm that static cytometry is a good and reliable method to evaluate DNA tumor content and considered a useful prognostic parameter for predicting recurrence rate, disease progression or survival in patients affected by bladder tumors. IntroductionTransitional cell carcinoma of the bladder is a tumor with variable biological potential (1); the recurrence rate is 50% to 70% (2) and as many as 19% of pTa and 34% of pT1 tumors will progress to muscle-invasive features (3). The ability to predict true tumor biological potential could facilitate patient treatment selection and improve the patient survival rate and quality of life.Various pathological and clinical parameters, such as tumor grade, stage, multifocality, size, rate and pattern of recurrence, association with Cis and other dysplastic urothelial lesions have been associated with a poor clinical outcome (4). Histopathological stage and grade are conventional prognostic factors for predicting biological behavior (5).To increase understanding of the cellular mechanisms underlying the development of bladder carcinoma and its natural history, many groups of potential molecular markers and quantitative morphometric methods have been described over the years (6). DNA ploidy identification has been proposed (since the late 1970s) as a diagnostic (7) and prognostic method to evaluate the malignant potential in several neoplasms, such as ovarian (8), endometrial (9) or colorectal cancers (10). Moreover, other studies demonstrated that nuclear DNA content...

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“…2004). The incidence rates of bladder cancer are the highest in developed countries (Ioakim‐Liossi et al. 1999).…”

mentioning

confidence: 99%

“…2006). This technique provides useful information concerning DNA content in a given population of cells (Ioakim‐Liossi et al. 1999).…”

mentioning

confidence: 99%

DNA study of bladder papillary tumours chemically induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine in Fisher rats

Oliveira

Adega

Palmeira

et al. 2006

Int J Experimental Path

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To examine DNA abnormalities in bladder papillary tumours induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in female rats, using image cytometric DNA analysis and cytogenetics. Thirty female rats were exposed to BBN in their drinking water for 20 weeks. One group of 10 animals served as controls. The animals exposed to BBN were killed at a rate of two per week, with the bladder being collected under aseptic conditions and those tumours with exophytic growth removed. The nuclear DNA content of the tumours was evaluated using image cytometric analysis. In two rats part of the tumour pieces was stipulated for culturing. Cytogenetic analysis was performed on at least 30 cells from each cell population and on both tumours. Papillary carcinomas were classified as low grade and high grade. DNA ploidy studies were carried out on 28 low-grade and 21 high-grade papillary carcinomas. Histograms obtained by image analysis showed that a normal urothelium was diploid; 28.6% and 100% of low-and high-grade papillary carcinomas were aneuploid respectively. Both tumours used for cell culture showed multiple numerical and structural chromosome alterations and several marker chromosomes. Image cytometric DNA analysis proved to be a good and reliable method for examining DNA alterations in papillary bladder carcinomas. The present findings establish that the DNA content is statistically different between low-grade and high-grade papillary carcinomas and that deviation from the diploid number is markedly higher in the high-grade ones. In addition, the occurrence of marker chromosomes seems to be related to the aggressiveness of the tumour.

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Image Cytometric DNA Analysis and Proliferating Cell Nuclear Antigen (PCNA) Expression in Transitional Cell Carcinoma of the Bladder

Cited by 6 publications

References 14 publications

Expression of p120, Ki‐67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value

Expression of p120, Ki‐67 and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic value

Prognostic value of static cytometry in transitional cell carcinoma of the bladder: Recurrence rate and survival in a group of patients at 10 years follow-up

DNA study of bladder papillary tumours chemically induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine in Fisher rats

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