Tumor Growth Fraction Estimation, Perturbation, and Prognostication

Braunschweiger, Paul G.

doi:10.1007/978-1-60327-406-7_3

Cited by 8 publications

(3 citation statements)

References 23 publications

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“…Binucleated hepatocytes were scored as a single hepatocyte. The growth fraction (21), an estimation of hepatocytes active in the cell cycle, was quantitated by dividing the total number of PCNA stained hepatocytes (GI + S + G2+ M) by the total number of hepatocytes counted (at least 1000 hepatocytes).…”

Section: Cell Proliferation Countsmentioning

confidence: 99%

Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats.

Foley

Ton

Maronpot

et al. 1993

Environ Health Perspect

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Proliferating cell nuclear antigen (PCNA), an endogenous nuclear protein, has recently been used to identify replicating cells. PCNA was compared to tritiated thymidine ([3H]-TdR), a reliable and accurate exogenous labeling agent, to ascertain if PCNA gives comparable results for quantitative cell proliferation. Male F344 rats were treated with a single dose of 500 mg/kg 4-acetylaminofluorene (4-AAF), a known liver mitogen. Rats (n = 5) were euthanized and necropsied at 6, 12, 18, 24, 36, 48, 96, or 192 hr after treatment. Two hours before necropsy, rats were pulsed-dosed with [3H]-TdR (2 mCi/kg body weight). Livers were sectioned, autoradiography performed, and labeling indexes (LI), a measurement of the percentage of S-phase hepatocytes, determined. One and a half years after the completion of this study, the archival paraffin blocks of the liver tissue were sectioned and stained for PCNA by an immunohistochemical procedure. Immunocytochemical staining patterns of proliferating cell nuclear antigen antigen expression permitted the recognition of G1, S, G2, M, and quiescent cells. PCNA LI, generated by scoring only cells exhibiting S-phase staining patterns, was compared to the pulse [3H]-TdR LI for each animal. Similar periportal staining patterns of S-phase nuclei were detected by both markers. The [3H]-TdR LI and the PCNA LI exhibited a peak at 24 hr of approximately the same magnitude. However, while the [3H]-TdR LI had returned to near baseline at the 48-hr time point, the PCNA LI remained elevated until the 96-hr time point. This sustained elevation of the PCNA index cannot be explained at this time.(ABSTRACT TRUNCATED AT 250 WORDS)Imagesp201-aFIGURE 2. AFIGURE 2. BFIGURE 2. CFIGURE 2. DFIGURE 2. EFIGURE 2. FFIGURE 2. GFIGURE 2. H

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Section: Cell Proliferation Countsmentioning

confidence: 99%

Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats.

Foley

Ton

Maronpot

et al. 1993

Environ Health Perspect

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“…Early attempts, bascd on the use of tritiated thymidine (I'HIdT) to measure the percentage of DNA synthesizing cells o r tumour growth fraction. were cumbersome and did not gain widc clinical application (Mendelsohn 1962, Braunschweiger 1987. Among ncw approaches, thc estimate of S phase fraction by flow cytometry, either based on direct DNA content analysis (Darzynkiewicz 1992) or by immunochemical detection of bromodeoxyuridine (BrdUrd) incorporation (Gray et al 1987), are gaining wide acceptance.…”

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confidence: 99%

Cell cycle dependent expression and stability of the nuclear protein detected by Ki‐67 antibody in HL‐60 cells

1992

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The expression and stability of the proliferation-associated nuclear antigen detected by Ki-67 antibody have been investigated in human promyelocytic leukaemic HL-60 cells in relation to their progression through the cell cycle. Expression of this antigen was minimal in late G1 and early S phase cells. The antigen accumulated in the cells predominantly during S phase, and its rate of increase per cell accelerated during the second half of this phase. The accumulation of Ki-67 antigen during S exceeded the increase in DNA content, and thus the Ki-67/DNA ratio rose 80% from late G1 to G2 + M. This antigen rapidly disappeared from post-mitotic cells. The half-life of this protein estimated in post-mitotic cells during stathmokinesis induced by vinblastine appeared to be shorter than 1 h. This rapid turnover should be compared with the relatively long (6-8 h) duration of G1 of the studied cells. In cells in which de novo protein synthesis was inhibited by 0.1 microgram/ml cycloheximide, the half-life of the Ki-67 antigen was also found to be about 1 h regardless of the cell position in the cell cycle. Thus, the data suggest that variations in the level of this protein during the cell cycle are a consequence of its different synthesis rate rather than phase-specific changes in the rate of its degradation. Because the late G1 and very early S phase cells express the antigen at levels only slightly above background, it is possible that, when using Ki-67 antibody as a marker of the cell growth fraction, some late G1 cells can be erroneously classified as non-cycling cells.

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“…However, the population of cells in mitosis can be considered a pure cycling cohort of (neoplastic) cells (Braunschweiger, 1987) and its assessment in human turnouts has been associated with other biological parameters to predict tumour behaviour and can be useful for the planning of a correct therapy (Uyterlinde et a]., 1988;Baak, 1990;Chieco et al, 1991). Recently, a large multicentre study emphasized the importance of the mitotic index for the prognosis of human breast cancer (van Diest et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

A rapid and simple staining method, using Toluidine Blue, for analysing mitotic figures in tissue sections

Chieco¹,

Pagnoni²,

Romagnoli³

et al. 1993

Histochem J

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Mitotic index is a clinically important parameter in cancer pathology. We developed a staining method using Toluidine Blue to detect efficiently and rapidly mitotic figures in sections of formalin-fixed paraffin-embedded human and rat tissues. Sections were stained at acid pH with a 0.01% Toluidine Blue solution after removal of RNA with hydrochloric acid or ribonuclease. The optimal pH of the TB staining solution was found to be 4.5 for rat tissues and 3.5 for human tissues. This procedure stained mitotic figures much more intensely than other (extra)cellular structures. A quantitative estimate of the total number of nuclei in the field where mitotic figures were counted, was obtained in an adjacent section hydrolysed in 5 N hydrochloric acid and stained by the Feulgen reaction with a Schiff-type reagent containing 0.01% Toluidine Blue. This method specifically stained interphase and mitotic nuclei and the field cellularity could be quantified by image cytometry. When these procedures were performed on two consecutive serial sections, a mitotic index could be determined accurately by relating the count of mitotic figures to the number of tumour cells.

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Tumor Growth Fraction Estimation, Perturbation, and Prognostication

Cited by 8 publications

References 23 publications

Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats.

Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats.

Cell cycle dependent expression and stability of the nuclear protein detected by Ki‐67 antibody in HL‐60 cells

A rapid and simple staining method, using Toluidine Blue, for analysing mitotic figures in tissue sections

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