Summary
In an attempt to determine whether the fluorescent in situ hybridization (FISH) can be used as a rapid approach for the identification of aneuploidy in premalignant cervical smears, a centromeric probe for chromosome 1 was used. The results from the FISH experiments were compared with measurements of the overall DNA content obtained by means of an image analysis system. With progression to neoplasia, a decrease of the frequency of cells with two spots was observed, due to an increasing polysomy of chromosome 1. As far as the DNA content was concerned, an increasing DNA index and 5C-exceeding ratio (fraction of cells with a DNA content higher than 5C) was observed. Classification of the FISH results by a linear discriminant analysis revealed that 67.6% of the cases were classified in agreement with the CIN classification. These data suggest that chromosome 1 may be considered as a marker chromosome for pre-malignant cervical lesions and that the DNA content measurements are complementary to the FISH results.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
adhvaryu, s. g., vyas, r. c., dave, b. j., trivedi, a. H. & parikh, b. N. (1985) Spontaneous and induced sister chromatid exchange frequencies and cell cycle progression in lymphocytes of patients with carcinoma of the uterine cervix. Cancer Genet. Cytogenet. 14, 67–72.
arnoldus, e. p. j., noordermeer, i. a., peters, a. c. b., voormolen, j. h. c., bots, g. t. a. m., raap, a. k. & van derploeg, m. (1991) Interphase cytogenetics of brain tumors. Genes, Chromosomes Cancer 3, 101–7.
atkin, n. b. (1989) Solid tumor cytogenetics: progress since 1979. Cancer Genet. Cytogenet. 40, 3–12.
atkin, n. b. & kay, r. (1979) Prognostic significance of model DNA value and other factors in malignant tumours, based on 1465 cases. Br. J. Cancer 40, 210–21.
atkin, n. b., baker, m. c. & fox, m. f. (1990) Chromosome changes in 43 carcinomas of the cervix uteri. Cancer Genet. Cytogenet. 44, 229–41.
bernstam, v. a. (1993) Tumors of the uterine cervix and endometrium. In Pocket Guide to Gene Diagnostics in Clinical Practice (edited by bernstam, v. a.), pp. 167–71. Boca Raton-Florida: CRC Press.
bibbo, m., bartels, p. h., dytch, h. E. & wied, g. l. (1985) Ploidy patterns in cervical dysplasia. Analyt. Quant. Cytol. Histol. 7, 213–7.
bocking, a. (1991) DNA-cytometric diagnosis of prospective malignancy in borderline lesions of the uterine cervix. In Recent Results in Cancer Research: Primary Prevention and Cancer (edited by Eylenbosch, w. j., kirsch-volders, m., deleener, a. & weyler, j.), pp. 106–15, Berlin: Springer-Verlag.
buroker, n., bestwick, r., haight, g., magenis, r. e. & litt, m. (1987) A hypervariable repeated sequence on human chromosome 1p36. Hum. Genet. 77, 175–81.
chen, l. c., neubauer, a., kurisu, w., waldman, f. m., ljung, b. m., goodson, w., goldman, e. s., moore, d., balazs, m., liu, e., mayall, b. h., & smith, h. s., (1991) Loss of heterozygosity on the short arm of chromosome 17 is associated with high proliferative capacity and DNA aneuploidy in primary human breast cancer. Proc. Natl Acad. Sci. USA 88, 3847–51.
cooke, m. j. & hindley, j. (1979) Cloning of human satellite III DNA: different components are on different chromosomes. Nuc. Acid Res. 6, 3177–97.
cremer, t., tesin, d., hopman, a. h. n., & manuelidis, l. (1988) Rapid interphase and metaphase assessment of specific chromosomal changes in neuroectodermal tumor cells by in situ hybridization with chemically modified DNA probes. Exp. Cell Res. 176, 199–220.
deleener, a., gunst, j., vanderkerken, k. & kirsh-volders, m. (1991) Quantitative image analysis and flow cytometry can improve early detection of cancer. In Recent Results in Cancer Research: Primary Prevention and Cancer (edited by eylenbosch, w. j., kirsch-volders, m., deleener, a. & weyler, j.), pp. 42–51, Berlin: Springer-Verlag.
devilee, p., van derploeg, m. & vooys, c. p. (1988) In situ hybridization as a tool to study numerical chromosome aberrations in solid bladder tumors. Histochemistry 89, 307–16.
devilee, p., vanvliet, m., bardoel, a., kievits, t., kuipers-dijkshoorn, n., pearson, p. l. & cornelisse, c. j. (1991) Frequent somatic imbalance of marker alleles for chromosome 1 in human primary breast carcinoma. Cancer Res. 51, 1020–5.
frielander, m. l., hedley, d. w. & taylor, i. w. (1984) Clinical and biological significance of aneuploidy in human tumours. J. Clin. Pathol. 37, 961–74.
hanselaar, a. g. j. m., vooijs, g. p., vanthof-grootenboer, a. e., gemmink, j. h., deleeuw, j. & pahlplatz, m. m. m. (1991) Cystophotometric analysis of corresponding cytological and cervical intraepithelial neoplasia Grade III specimens. Cytometry 11, 1–9.
hopman, a. h. n., ramaekers, f. c. s. & vooijs, g. p. (1990) Interphase cytogenetics of solid tumors. In In Situ Hybridization Principles and Practice (edited by polak, j. m. o'd., & mcgee, j.), pp. 165–86. Oxford: Oxford Science Publications.
jones, m. h. & nakamura, y. (1992) Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. Oncogene 7, 1631–4.
kiechle-schwarz, m., decker, h. h.-j., berger, c. s., fiebig, h. h. & sandberg, a. a. (1991) Detection of monosomy in interphase nuclei and identification of marker chromosomes using biotinylated alpha-satellite DNA probes. Cancer Genet. Cytogenet. 51, 23–33.
koss, l. g. (1993) Cervical (Pap) smear. Cancer 71, 1406–12.
kuo, w. l., tenjin, h., segraves, r., pinkel, d., golgbus, m. s. & gray, j. (1991) Detection of aneuploidy involving chromosomes 13, 18 or 21 by fluorescence in situ hybridization (FISH) to interphase and metaphase amniocytes. Am. J. Hum. Genet. 49, 112–9.
lukovic, l. & milasin, j. (1992) Sister chromatid exchange in patients with carcinoma in situ of the cervix uteri. Cancer Genet. Cytogenet. 59, 84–5.
murty, v. v. v. s., miltra, a. b., luthra, u. k. & singh, i. p. (1986) Sister chromatid exchanges in patients with precancerous and cancerous lesions of the cervix uteri. Hum. Genet. 72, 37–42.
narayanan, s. (1992) Overview of principles and current uses of DNA probes in clinical and laboratory medicine. Ann. Clin. Lab. Med. 22, 353–76.
nederlof, p. m., van derflier, s., raap, a. k., tanke, m. j., van derploeg, m., kornips, f. & geraedts, j. p. m. (1989) Detection of chromosome aberrations in interphase tumor nuclei by nonradioactive in situ hybridization. Cancer Genet. Cytogenet. 42, 87–98.
norusis, m. j. (1990) SPSS Advanced Statistics User's Guide. Chicago: SPSS Inc.
olah, e., balogh, e., kovacs, i. & kiss, a. (1989) Abnormalities of chromosome 1 in relation to human malignant diseases. Cancer Genet. Cytogenet. 43, 179–94.
pardue, m. & gall, j. (1969) Molecular hybridization of radioactive DNA of cytological preparations. Proc. Natl Acad. Sci. USA 64, 600–4.
poddighe, p. j., moesker, o., smeets, d., awwad, b. h. & ramaekers, f. c. s. (1991) Interphase cytogenetics of haematological cancer: comparison of classical karyotyping and in situ hybridization using a panel of eleven chromosome specific DNA probes. Cancer Res. 51, 1959–67.
poddighe, p. j., ramaekers, f. c. s., smeets, a. w. g. b., voojis, g. p. & hopman, a. h. n. (1992) Structural chromosome 1 aberrations in transitional cell carcinoma of the bladder: interphase cytogenetics combining a centromeric, telomeric, and library DNA probe. Cancer Res. 52, 4929–34.
raimondi, e., scariolo, s., desario, a. & decarli, l. (1989) Aneuploidy assays on interphase nuclei by means of in situ hybridization with DNA probes. Mutagenesis 4, 165–9.
ramaekers, f., hopman, a. & vooijs, p. (1992) Advances in the detection of ploidy differences in cancer by in situ hybridization. Anal. Cell Pathol. 4, 337–44.
reid, r. & fu, y. s. (1986) Is there a morphologic spectrum linking condyloma to cervical cancer? In Viral Etiology of Cervical Cancer, 21 Banbury Report (edited by peto, r. & zur Hausen, h.), pp. 91–113. New York: Cold Spring Harbor Laboratory.
sano, t., tsujino, t., yoshida, k., nakayama, h., haruma, k., ito, h., nakamura, y., kajiyama, g. & tamara, e. (1991) Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas. Cancer Res. 51, 2926–31.
segers, p., haesen, s., amy, j. j., desutter, p. h., vandam, p. & kirsh-volders, m. (1994) Detection of premalignant stages in cervical smears with a biotinylated probe for chromosome 1. Cancer Genet. Cytogenet. 75, 120–8.
sreekantaiah, c., bhargava, m. k. & shetty, n. j. (1988) Chromosome 1 abnormalities in cervical carcinoma. Cancer 62, 1317–24.
sreekantaiah, c., debraekeleer, n. & haas, o. (1991) Cytogenetic findings in cervical carcinoma: a statistical approach. Cancer Genet. Cytogenet. 53, 75–81.
srivatsan, e. s., misra, b. c., venugopalan, m. & wilczynski, s. p. (1991) Loss of heterozygosity for alleles on chromosome 11 in cervical carcinoma. Am. J. Hum. Genet. 49, 868–77.
teyssier, j. r. (1989) The chromosomal analysis of human solid tumors: a triple challenge. Cancer Genet. Cytogenet. 37, 125–30.
therman, e., sarto, g. e. & kuhn, e. m. (1986) The course of endomitosis in human cells. Cancer Genet. Cytogenet. 19, 301–10.
tsou, k., hong, d. & varello, m. (1984) Flow cytometric DNA analysis as a diagnostic aid for cervical condyloma and cancer. Cancer 54, 1778–87.
vandeken, h., pizzolo, j. g., reuter, v. e. & melamed, m. r. (1990) Cytogenetic analysis of human solid tumors by in situ hybridization with a set of 12 chromosome-specific DNA probes. Cytogenet. Cell Genet. 54, 103–7.
viegas-Péquignot, e., jeanpierre, m., dutrillaux, a. M., gerbault-seureau, m., muleris, m. & dutrillaux, b. (1989) Detection of 1q polysomy in interphase nuclei of human solid tumors with a biotinylated probe. Hum. Genet. 81, 311–4.
waldman, f. m., carroll, p. r., kerschmann, r., cohen, m. b., field, f. g. & mayall, b. h. (1991) Centromeric copy number of chromosome 7 is strongly correlated with tumor grade and labeling index in human bladder cancer. Cancer Res. 51, 3807–13.
yokota, k., ueda, k., ohama, k. & fujiwara, a. (1989) Increased spontaneous and mitomycin C-induced sister chromatid exchanges in patients with cancer of the cervix uteri, with special reference to stage of cancer. Cancer Genet. Cytogenet. 43, 79–87.
zheng, j., robinson, w. r., ehlen, t., yu, m. c. & dubeau, l. (1991) Distinction of low grade from high grade human ovarian carcinomas on the basis of losses of heterozygosity on chromosomes 3, 6, and 11 and HER-2/neu gene amplification. Cancer Res. 51, 4045–51.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Segers, P., Haesen, S., Castelain, P. et al. Study of numerical aberrations of chromosome 1 by fluorescent in situ hybridization and DNA content by densitometric analysis on (pre)-malignant cervical lesions. Histochem J 27, 24–34 (1995). https://doi.org/10.1007/BF00164169
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00164169