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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 17  |  Issue : 1  |  Page : 17-20

Does the presence of micronuclei in cervicovaginal smears help diagnose cancer early?


Depertmant of Pathology and Gynecology, University of Health Sciences, Fethi Sekin City Hospital, Elazig, Turkey

Date of Submission16-Jan-2020
Date of Acceptance28-Jan-2020
Date of Web Publication30-May-2020

Correspondence Address:
Dr. Özgen Arslan Solmaz
Depertmant of Pathology, University of Health Sciences, Fethi Sekin City Hospital, 23100 Elazig
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njbcs.njbcs_11_19

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  Abstract 


Context: The presence of micronuclei is an indicator of chromosomal instability, which may be associated with cancer. Cervical smears, which are commonly used in cervical carcinoma screening, are non-invasive samples of exfoliated epithelial cells, such as buccal mucosa cells. Aims: We aimed to demonstrate the association between micronucleus frequency and cancer if any was present. Settings and Design: This retrospective study was performed in our laboratory. A total of 4500 conventional cervical smears screened in the past 3 years (January 2015–2018) were included in the study. Materials and Methods: Cervical smear samples of 4000 patients, all of cytologic samples, were analysed using light microscopy under oil immersion (×1000) for the determination of micronuclei. The health information of patients with micronuclei was viewed in the hospital information system, and we investigated whether they had malignant tumours. Statistical Analysis Used: The Chi-square test was performed. Results: One hundred and forty-seven patients had micronuclei, and 3853 had none. Malignant tumours were detected in 29 of the 147 patients, no tumour was detected in 118. A statistically significant correlation was found between the presence of micronuclei and the presence of malignant epithelial tumours in the body and in the presence of micronuclei in cervical smears (P < 0.05). Conclusions: We found that the incidence of malignant epithelial tumours was 108.58-fold higher in cases with micronucleus than those without micronucleus. We believe that we can detect both cervical pathologies and epithelial tumours in other organs using the same test and that this finding should be transferred to pathology reports.

Keywords: Cancer, cervix, micronucleus


How to cite this article:
Solmaz &A, Kahraman G. Does the presence of micronuclei in cervicovaginal smears help diagnose cancer early?. Niger J Basic Clin Sci 2020;17:17-20

How to cite this URL:
Solmaz &A, Kahraman G. Does the presence of micronuclei in cervicovaginal smears help diagnose cancer early?. Niger J Basic Clin Sci [serial online] 2020 [cited 2020 Aug 3];17:17-20. Available from: http://www.njbcs.net/text.asp?2020/17/1/17/285461




  Introduction Top


Despite developments in early diagnosis and treatment, cancer is still an important health problem. When the incidence, mortality and prevalence of cancer worldwide were examined by the Internal Agency for Research on Cancer in 2018, it was reported that there were 18,078,957 new cancer cases and 9.6 million deaths. Lung (2.09 million), breast (2.08 million) and colorectal cancers (1.8 million) are the most common cancers.[1]

It is well established that early diagnosis and screening programmes are crucial in the fight against cancer. It has been demonstrated with studies that early diagnosis decreases mortality in breast, cervical, colon and skin cancers, and screening tests should be performed for these cancers in particular.[2],[3] Tests that will be used in screening have to be acceptable by people, who will be screened, practical, non-invasive and safe.[3]

Some recent studies have focused on determining screening tests to define if there is cancer within the body. Micronucleus screening is one of these suggested tests.[4],[5],[6],[7],[8] Micronucleus is declarative of either a fragmented or whole chromosomes extruded from the main nucleus during the process of mitosis. These acentric fragments or lost chromosomes give rise to small nuclei, which appear similar to the main nuclei on staining, known as micronuclei. Therefore, a micronucleus assay is an ideal parameter to serve as a biomarker in this regard, the presence of micronuclei is a sign of genomic instability.[5],[8],[9] Micronuclei are being screened in buccal smears to determine genetic damage in epithelial cells, which is correlated with epithelial cancers.[4],[5],[6],[7],[8]

Cervical smears, which are commonly used in cervical carcinoma screening, are non-invasive samples of exfoliated epithelial cells, such as buccal mucosa cells. We thought that micronuclei seen in epithelial cells might be a clue in the diagnosis of other organ carcinomas in cervical smears, just like in buccal mucosa scans, and we decided to investigate.


  Materials and Methods Top


This retrospective study was performed in our laboratory. The study was approved by the local ethics committee. Four thousand and five hundred conventional cervical smears screened in the past 3 years (January 2015–2018) were included in the study. The Papanicolaou-stained cervical smear samples of these patients were re-evaluated. They were fixed with a spray. All cytologic samples were analysed using light microscopy under oil immersion (×1000) for the determination of micronuclei. Smears free of Trichomonas vaginalis and candida infections were selected because it was reported in some studies that these infections might lead to micronuclei formation.[10],[11] Accordingly, 4000 patients were included in the study. Cells with degeneration and apoptosis were not included. Counting was avoided in cell clusters and clumps. The evaluation was made as positive or negative for micronuclei.

In the evaluation of the presence of micronuclei, the criteria determined by Thomas et al. were used.[12] According to these criteria: (1) a micronucleus must be less than one-third of the size of the main nucleus and (2) staining characteristics must be the same as the main nucleus [Figure 1]. The health information of the patients with micronuclei was viewed in the hospital information system, and we investigated whether they had malignant tumours.
Figure 1: Micronucleus Papanicolaou ×400 (arrow)

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Statistical analyses

All statistical analyses were performed using the Statistical Package for the Social Sciences Software (Windows version 17.0; SPSS Inc., Chicago, IL, USA). The Chi-square test was performed. Descriptive statistics were used to determine the odds ratio. P < 0.05 was considered statistically significant.


  Results Top


A total of 4000 patients were evaluated. The mean age was 41 years. One hundred and forty-seven (3.67%) patients had micronuclei and 3853 (96.33%) had none. Malignant tumours were detected in 29 of the 147 patients (19.7%); no tumour was detected in 118 (80.3%) patients. Seventeen of the patients with malignant tumours had breast carcinoma, three had gastric adenocarcinoma, two had colon adenocarcinoma, two had cervix carcinoma, three had bladder carcinoma, one had oral mucosa carcinoma and one patient had malignant melanoma. Malignant epithelial tumours were seen in seven of the 3853 (0.1%) patients without micronuclei. Three of these patients had squamous cell carcinoma of the skin, two had adenocarcinoma in the colon and two patients had gastric adenocarcinoma [Table 1].
Table 1: Malignant tumours in patients with and without micronuclei

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A statistically significant correlation was found between the presence of micronuclei and the presence of malignant epithelial tumours in the body and in the presence of micronuclei in cervical smears (P< 0.05), the incidence of malignant epithelial tumours was 108.58-fold higher in cases with micronucleus than those without micronucleus. The sensitivity was 80%, the specificity was 97% and the test validity was 96%.


  Discussion Top


In this study, we investigated whether there was a relationship between the presence of micronuclei and the presence of epithelial tumours. There was a 108.58-fold increase in the frequency of malignant epithelial tumours in patients with micronuclei compared with non-micronuclei patients.

Nowadays, cancer is the most commonly studied disease. However, it has more than one definition; it is the uncontrollable reproduction of cells as a result of impairments in regulatory mechanisms of the cell cycle.[13] Cancer begins with an alteration of a single cell with the involvement of various genetic and biochemical factors. Although cancers of different tissues exhibit different features, most cancers are associated with DNA mutations or chromosomal aberrations.[14] Therefore, various diagnostic methods for cancers, in which bioindicators in DNA or chromosomal levels have been developed.[15]

For protection against cancer, it is important to detect any risk conditions early to intervene in the changeable factors responsible for the disease. Molecular epidemiology could represent an effective approach for primary prevention, which may overcome the limits of classic epidemiology based on health damages that have already occurred. In essence, it allows for the evaluation of early molecular alterations predictive of the origin of tumour pathologies.[16] Recent prospective studies evaluating large cohorts of disease-free individuals revealed that increases in micronuclei frequency were associated with an increased risk of cancer at the population level, providing suggestive evidence that this biomarker could be predictive of cancer risk.[17]

Chromosomal aberrations have become prominent in research concerning the early diagnosis of cancer. In a study by Bonassi et al. on Italian and Swedish populations, it was revealed that metaphase chromosomal aberrations increased the risk for cancer 2.3–2.6-folds.[4] Micronucleus screening is suggested as a new way of screening cancer in the body. Retrospective studies suggested that the prevalence of micronuclei is gradually increasing in many types of cancer in the body.[6],[7],[8] Studies investigating micronuclei rates in cancers of some organs have been performed, and micronuclei with an extremely increased rate have been found compared with control groups.[15],[18] In a study concerning cervical cancer that was conducted by Venkatachalam et al.,[19] it was determined that micronuclei were found 2.5-fold more frequently in patients with cancer compared with the control group. In a study by Murgia et al.[20] on digestive and respiratory tract tumours, an increase in micronuclei presence of 3.1-fold was found, and similarly, Milosević-Djordjević et al.[21] reported a 2.4-fold increase in micronuclei presence in pharyngeal, breast and uterine cancers.

Dey et al.[22] compared micronuclei assays of buccal smears of 32 patients with breast carcinoma and 49 patients with benign breast lesions and determined a statistically significantly more common micronuclei presence in the malignant group (2.19 ± 1.08 vs. 0.50 ± 0.45, P < 0.001). In a recent study performed on Mexican women, buccal cell samples of 21 patients with breast cancer were compared with those of 20 healthy females in regards to micronuclei frequency, and a significantly increased frequency was reported in patients with breast cancer.[23] These studies also support our findings even though they were performed with buccal smears, not cervical smears.

In another recent study, Verma and Dey [24] investigated the association of counts of chromatin bridges, multipolar mitoses per smear and micronuclei and nuclear budding with the cytologic grade of breast cancer in fine-needle aspiration cytology (FNAC) specimens of 55 patients with invasive ductal carcinoma. The authors reported the mean number of micronuclei/1000 malignant cells as 1.2 (±1.7), 3.7 (±2.1) and 12.2 (±5.1) in patients with Grade I, Grade II and Grade III breast cancer, respectively, establishing a strong correlation of micronuclei presence with cytological grading. In that study, the micronuclei count was investigated in FNAC samples, and we also determined a significantly increased micronuclei presence in FNAC samples in our study. Similar to our results, Samanta et al.[25] also reported that the mean micronuclei scores of women with invasive ductal carcinoma in FNAC were statistically significantly higher than those of patients with fibroadenoma.

The determination of the presence of micronuclei in the body has also been suggested as a screening tool for some cancers in the body.[26],[27] To the best of our knowledge, there are few studies in literature about the association of micronuclei in cervical smear samples with carcinoma. The primary goal of screening programmes for cancer is to reduce mortality due to cancer with early diagnosis. Screening tests should be relatively easy, reliable and reproducible; and micronuclei scoring in cervical smear samples fulfil these criteria. Accordingly, larger studies are warranted to determine the role of micronuclei scoring in cervical smear samples as a screening test.


  Conclusions Top


Micronucleus describes genetic damage to epithelial cells and is associated with epithelial cancers. On micronucleus examination in the cervical smear, we found that the incidence of malignant epithelial tumours in any organ of the body was 108.58 times higher than in those without micronucleus. Thus, the presence of micronucleus in cervical smears, which is an easily applicable test, can be considered as a screening tool for the detection of epithelial tumours in the body. We believe that using the same test, we can detect both cervical pathologies and the risk of epithelial tumours in other organs. Therefore, we think that this finding should be transferred to pathology reports, and tumour screening can be performed in patients with micronucleus.

Acknowledgements

Clinical information collection and statistical evaluation were performed by Özgen Arslan Solmaz and Gülcan Kahraman.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Flores-Garcia A, Torres-Bugarin O, Salvador Velarde-Félix J, Rangel-Villalobos H, Zepeda-Carrillo EA, Rodríguez-Trejo A, et al. Micronuclei and other nuclear anomalies in exfoliated buccal mucosa cells of Mexican women with breast cancer. J BUON 2014;19:895-9.  Back to cited text no. 23
    
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