Immunocytochemical Demonstration of S Phase Cells by Antlbromobeoxyuribine Monoclonal Antibody in Human Prostate Adenocarcinoma

Abstract

Using a monoclonal antibody to bromodeoxyuridine and immunohistochemistry, we measured the incorporation of this thymidine analogue into the deoxyribonucleic acid of human prostate adenocarcinoma cells exposed in situ. Fifteen patients with prostate cancer were given an intravenous infusion of 500 mg. bromodeoxyuridine at needle biopsy to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method using anti-bromodeoxyuridine monoclonal antibody as the first antibody. The results showed that this method demonstrated bromodeoxyuridine-labeled nuclei satisfactorily in tissue section. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. Grade 3 tumors averaged 4.37 +/- 0.48 per cent labeling versus 2.41 +/- 0.49 per cent in grade 2 tumors, and grade 1 tumor in the series had an S phase fraction of 1.36 +/- 0.39 per cent. The average S phase fractions for single gland, cribriform, fused and medullary were 1.16, 2.30, 3.74 and 4.95 per cent, respectively. The results obtained with S phase fraction measured with bromodeoxyuridine labeling proved to be comparable to the results of histological grade and growth pattern. Thus, the higher S phase fraction may indicate biological malignancy. Moreover, the degree of heterogeneity concerning S phase fraction distribution within prostate cancer tissue could be compared to the morphological appearance. Our preliminary results suggest that the measurement of bromodeoxyuridine labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

Clinical Observations on the Doubling Time of Prostate Cancer

“…The probability of being diagnosed with a substantial cancer in a man's lifetime is 8% and 3% will eventually die from it. Therefore, there is the overriding dilemma as to which cancers should be diagnosed and which ones should be treated.Experimental studies and animal models have shown that prostate cancer has a slow growth rate when com pared to other tumors [5], On the basis of indirect evi dence from volumes of incidental carcinomas in an au topsy series, it has been proposed that prostate cancer fol lows a simple exponential growth curve with a constant long doubling time throughout its entire natural history [2], However, these determinations fail to reveal whether there is prognostic predictability in the histologic evolu tion of cancer with time. They are based on morphologic evaluation at a single point in time.…”

Proliferating Cell Nuclear Antigen in Needle Biopsy Specimens of Prostatic Carcinoma

“…As shown in the study with BrdU immunostaining [4], there was a significant difference in the PCNA index according to the glandular pattern of prostatic carcinoma. The proliferative activity of solid carcinomas was significantly higher than that of separate gland carcinomas and trabecular/fused gland carcinomas.…”

“…It has been demonstrated that the proliferative activity of tumors is correlated with metastatic potential, recur rence and overall prognosis [1], Studies regarding the pro liferative activity of such tumors have up to now been mainly performed using flowcytometry [2], the incorpora tion of radiolabeled materials such as tritiated thymidine [3] and bromodeoxyuridine (BrdU) [4], and monoclonal antibodies such as Ki-67 [5,6]. Immunohistochemical methods of assessing cell proliferation have advantages and incubated at 4°C overnight.…”

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

“…Proliferation activity in prostate cancer has been assessed by immunohistochemistry using Ki-67 monoclonal antibody (16,17), PCNA (18) and tritium[ 3 H]-thymidine or bromodeoxyuridine labeling (19,20). Some studies demonstrated progressively rising levels of proliferative index (PI) values from PIN to invasive and metastatic carcinoma, illustrating the cancer progression (19,20). The mean PI values have been shown to range from 1.7 to 17.6% indicating low cell turnover consistent with a natural slow disease progression.…”