Apoptosis and micronucleus in cervical pap smears: promising assays to increase the diagnostic value of the test.
Keywords:
apoptosis, cervical, correlation, micronucleus, Pap smear.
Abstract
Background: The micronucleus (MN) test on exfoliated cells has been successfully used to screen population groups at risk for cancers of cervix, oral cavity, esophagus and urinary bladder. MN originates from chromatin fragments or whole chromosomes; their presence in cells is a reflection of chromosomal aberration. Their frequency rises in carcinogen-exposed tissues much earlier than the symptoms. Apoptosis is easily discernible in cervical Pap smears in the form of karyorrhexis, karyolysis and condensation of chromatin. Very few studies are available in literature have studied the significance of MN scoring and apoptosis in cervical non-neoplastic, pre-neoplastic and neoplastic conditions.We compared the MN score and apoptosis in the whole spectrum of cervical lesions and also evaluated the role of MN score and apoptosis as biomarkers in different non-neoplastic, pre-neoplastic and neoplastic lesions.Aim: This is a retrospective study to evaluate the significance of apoptosis and micronucleus counts in the spectrum of lesions in cervical pap smears.Methods: It was a retrospective study conducted using Papanicolau stained cervical smears archived in the department of pathology. We evaluated a total of 230 cases, which included 63 normal smears, 106 inflammatory smears, 15 smears of Atypical squamous cells of undetermined significance, 20 smears of Low grade squamous intraepithelial neoplasm, 12 smears of high grade squamous intraepithelial neoplasm, and 14 smears of invasive carcinoma. Two pathologists separately and independently counted the number of cells with micronucleus and the number of apoptotic cells per 1,000 squamous epithelial cells.Results: Micronucleus score was higher in invasive carcinoma and preneoplastic conditions of cervix than the normal and inflammatory conditions. Apoptotic cells were more in preneoplastic lesions and invasive carcinomas as compared normal and inflammatory conditions except in case of inflammatory atrophic smears and erosions of cervix. There was a positive correlation between micronucleus score and apoptosis in the study groups.Conclusion: Micronucleus score and apoptotic cells increases with increasing grade of dysplasia. It is maximum in malignancy and minimal in normal and inflammatory smears. There is a positive correlation between increased apoptosis and high micronucleus score. These two additional features increase the accuracy of reporting.References
1. Gandhi G, Kaur B. Elevated frequency of Micronuclei in uterine smears of cervix cancer patients. Caryologia. 2003;56:217–22.
2. Kalyani R, Das S, Bindra Singh MS, Kumar H. Cancer profile in the Department of Pathology of Sri Devaraj Urs Medical College, Kolar: A ten years study. Indian J Cancer. 2010;47:160–5.
3. Aires G.M.A., Meireles J.R.C., Oliveira P.C, Oliveira J.L., Araújo E.L., Pires B.C., Cruz E.S.A., Jesus N.F,. Pereira C.A.B and Cerqueira E.M.M. Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix. Genetics and Molecular Research 2011; 10 (3): 1558-64 .
4. Shoji Y, Saegusa M, Takano Y, Ohbu M, Okayasu I. Correlation of apoptosis with tumour cell differentiation, progression, and HPV infection
in cervical carcinoma. J. Clin Pathol. 1996;49:134-8
5. Palve DH, Tupkari JV. Clinico-pathological correlation of micronuclei in oral squamous cell carcinoma by exfoliative cytology. Oral and Maxillofac Pathol. 2008;12:2–7.
6. Khanna S, Purwar A, Singh NN, Sreedhar G, Singh S, Bhalla S. Cytogenetic biomonitoring of premalignant and malignant oral lesions by micronuclei assessment: A screening evaluation. Eur J Gen Dent 2014;3:46-52.
7. Shashikala R, Indira AP, Manjunath GS, Rao KA, Akshatha BK. Role of micronucleus in oral exfoliative cytology. J Pharm Bioall Sci 2015;7:S409-13.
8. Bueno CT, da Silva CMD, Barcellos RB, et al. Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test. Genetics and Molecular Biology 2014;37:496-9.
9. Fareed M, Afzal M, Siddique YH. Micronucleus investigation in buccal mucosal cells among pan masala/gutkha chewers and its relevance for oral cancer. Biology and Medicine 2011;3:8-15.
10. Naderi N J, Farhadi S, Sarshar S. Micronucleus assay of buccal mucosa cells in smokers with the history of smoking less and more than 10 years. Indian J Pathol Microbiol 2012;55:433-8.
11. Guzmán P, Sotelo-Regil RC, Mohar A, Gonsebatt ME, et al. Positive correlation between the frequency of micronucleated cells and dysplasia in Papanicolaou smears. Environ Mol Mutagen. 2003;41:339–43. [PubMed: 12802804]
12. Milde-Langosch K, Riethforf S, Loning T. Association of human papilloma virus infection with carcinoma of the cervix uteri and its precursor lesions: [PubMed: 11037341]
13. Leal-Garza CH, Cerda-Flores RM, Leal-Elizondo E, Cortes-Gutierrez EI. Micronuclei in cervical smears and peripheral blood lymphocytes from women with and without cervical uterine cancer. Mutat Res. 2002;515:57–62. [PubMed: 11909754]
14. Samanta S, Dey P, Nijhawan R. Micronucleus in cervical intraepithelial lesions and carcinoma. Acta Cytol. 2011;55:42–7. [PubMed: 21135521]
15. Liao SY, Stanbridge EJ. Expression of the MN antigen in cervical Papanicolaou smears is an early diagnostic biomarker of cervical dysplasia. Cancer Epidemiol Biomarkers Prev. 1996;5:549–57. [PubMed: 8827360]
16. Patel B P, Trivedi PJ, Brahmbhatt MM, Shukla SN, Shah PM, Bakshi SR. Micronuclei and chromosomal aberrations in healthy tobacco chewers and controls: A study from Gujarat, India. Arch Oncol 2009;17(1-2):7-10.
17. Grover S, Mujib A, Jahagirdar A, Telagi N, Kulkarni P. A comparative study for selectivity of micronuclei in oral exfoliated epithelial cells. Journal of cytology / Indian academy of cytologists. 2012;29(4):230-5. doi:10.4103/0970-9371.103940.
18. Anitha B, Satheeshkumar B. A study on the role of micronuclei in assessing the progression of precancerous lesions of cervix and the diagnosis of carcinoma of cervix. Journal of evidence based medicine and healthcare. 2015;2(24): 3611-5.
19. Ambroise MM, Balasundaram K, Phansalkar M. Predictive value of micronucleus count in cervical intraepithelial neoplasia and carcinoma. Turk Patoloji Derg 2013, 29:171-8.
20. Gayathri BN, Kalyani, R Hemalatha A, and Vasavi B. Significance of micronucleus in cervical intraepithelial lesions and carcinoma
J Cytol. 2012 ; 29: 236–40.
21. Mergener M, Rhoden C R, Amantéa S L. Nuclear abnormalities in cells from nasal epithelium: a promising assay to evaluate DNA damage related to air pollution in infants. J Pediatr (Rio J). 2014;90:632-6.
2. Kalyani R, Das S, Bindra Singh MS, Kumar H. Cancer profile in the Department of Pathology of Sri Devaraj Urs Medical College, Kolar: A ten years study. Indian J Cancer. 2010;47:160–5.
3. Aires G.M.A., Meireles J.R.C., Oliveira P.C, Oliveira J.L., Araújo E.L., Pires B.C., Cruz E.S.A., Jesus N.F,. Pereira C.A.B and Cerqueira E.M.M. Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix. Genetics and Molecular Research 2011; 10 (3): 1558-64 .
4. Shoji Y, Saegusa M, Takano Y, Ohbu M, Okayasu I. Correlation of apoptosis with tumour cell differentiation, progression, and HPV infection
in cervical carcinoma. J. Clin Pathol. 1996;49:134-8
5. Palve DH, Tupkari JV. Clinico-pathological correlation of micronuclei in oral squamous cell carcinoma by exfoliative cytology. Oral and Maxillofac Pathol. 2008;12:2–7.
6. Khanna S, Purwar A, Singh NN, Sreedhar G, Singh S, Bhalla S. Cytogenetic biomonitoring of premalignant and malignant oral lesions by micronuclei assessment: A screening evaluation. Eur J Gen Dent 2014;3:46-52.
7. Shashikala R, Indira AP, Manjunath GS, Rao KA, Akshatha BK. Role of micronucleus in oral exfoliative cytology. J Pharm Bioall Sci 2015;7:S409-13.
8. Bueno CT, da Silva CMD, Barcellos RB, et al. Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test. Genetics and Molecular Biology 2014;37:496-9.
9. Fareed M, Afzal M, Siddique YH. Micronucleus investigation in buccal mucosal cells among pan masala/gutkha chewers and its relevance for oral cancer. Biology and Medicine 2011;3:8-15.
10. Naderi N J, Farhadi S, Sarshar S. Micronucleus assay of buccal mucosa cells in smokers with the history of smoking less and more than 10 years. Indian J Pathol Microbiol 2012;55:433-8.
11. Guzmán P, Sotelo-Regil RC, Mohar A, Gonsebatt ME, et al. Positive correlation between the frequency of micronucleated cells and dysplasia in Papanicolaou smears. Environ Mol Mutagen. 2003;41:339–43. [PubMed: 12802804]
12. Milde-Langosch K, Riethforf S, Loning T. Association of human papilloma virus infection with carcinoma of the cervix uteri and its precursor lesions: [PubMed: 11037341]
13. Leal-Garza CH, Cerda-Flores RM, Leal-Elizondo E, Cortes-Gutierrez EI. Micronuclei in cervical smears and peripheral blood lymphocytes from women with and without cervical uterine cancer. Mutat Res. 2002;515:57–62. [PubMed: 11909754]
14. Samanta S, Dey P, Nijhawan R. Micronucleus in cervical intraepithelial lesions and carcinoma. Acta Cytol. 2011;55:42–7. [PubMed: 21135521]
15. Liao SY, Stanbridge EJ. Expression of the MN antigen in cervical Papanicolaou smears is an early diagnostic biomarker of cervical dysplasia. Cancer Epidemiol Biomarkers Prev. 1996;5:549–57. [PubMed: 8827360]
16. Patel B P, Trivedi PJ, Brahmbhatt MM, Shukla SN, Shah PM, Bakshi SR. Micronuclei and chromosomal aberrations in healthy tobacco chewers and controls: A study from Gujarat, India. Arch Oncol 2009;17(1-2):7-10.
17. Grover S, Mujib A, Jahagirdar A, Telagi N, Kulkarni P. A comparative study for selectivity of micronuclei in oral exfoliated epithelial cells. Journal of cytology / Indian academy of cytologists. 2012;29(4):230-5. doi:10.4103/0970-9371.103940.
18. Anitha B, Satheeshkumar B. A study on the role of micronuclei in assessing the progression of precancerous lesions of cervix and the diagnosis of carcinoma of cervix. Journal of evidence based medicine and healthcare. 2015;2(24): 3611-5.
19. Ambroise MM, Balasundaram K, Phansalkar M. Predictive value of micronucleus count in cervical intraepithelial neoplasia and carcinoma. Turk Patoloji Derg 2013, 29:171-8.
20. Gayathri BN, Kalyani, R Hemalatha A, and Vasavi B. Significance of micronucleus in cervical intraepithelial lesions and carcinoma
J Cytol. 2012 ; 29: 236–40.
21. Mergener M, Rhoden C R, Amantéa S L. Nuclear abnormalities in cells from nasal epithelium: a promising assay to evaluate DNA damage related to air pollution in infants. J Pediatr (Rio J). 2014;90:632-6.
Published
2016-10-25
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