Significance of the apoptotic index, mitotic index, and turnover index in premalignant and malignant squamous cell lesion of the oral cavity: How much is their diagnostic and prognostic role?

Preeti Singh; Vijay Kumar; Ganesh Singh; Anshu Singh; Ankita Singh

doi:10.4103/jss.JSS_24_19

ORIGINAL ARTICLE

Year : 2019 | Volume : 46 | Issue : 2 | Page : 49-52

Significance of the apoptotic index, mitotic index, and turnover index in premalignant and malignant squamous cell lesion of the oral cavity: How much is their diagnostic and prognostic role?

Preeti Singh¹, Vijay Kumar¹, Ganesh Singh², Anshu Singh¹, Ankita Singh¹
¹ Department of Pathology, L.L.R.M. Medical College, Meerut, Uttar Pradesh, India
² Department of Community Medicine, L.L.R.M. Medical College, Meerut, Uttar Pradesh, India

Date of Web Publication

28-Jan-2020

Correspondence Address:
Dr. Vijay Kumar
Department of Pathology, L.L.R.M. Medical College, Meerut, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jss.JSS_24_19

Abstract

Background: Carcinoma of the oral cavity is one of the most common cancers in our country. High mitotic index (MI) rate with growth, proliferation, and carcinoma of tissue linked with a lower survival rate. The combination of MI screening with proliferation and apoptotic assay is more compelling and comprehensive give more conclusion about anti-proliferative targets. Aim: The study aimed to show the impact of the apoptotic index (AI), MI, and turnover index (TI) to access the behavior of the lesion. Materials and Methods: A total of 68 histologically proven cases of premalignant and malignant squamous cell carcinoma were analyzed over a period of 1 year. Biopsy specimen with hematoxylin and eosin-stained sections was evaluated and correlated with different grade of the oral lesion with AI, MI, and TI. Results: Statistical analysis in premalignant between mild, moderate, and severe dysplasia shows no significant difference, whereas premalignant and malignant show a significant difference. Conclusion: Apoptotic, mitotic, and turnover base index can provide useful information and prediction of the nature of the lesion.

Keywords: Apoptotic index, mitotic index and turnover index, oral squamous cell carcinoma

How to cite this article:
Singh P, Kumar V, Singh G, Singh A, Singh A. Significance of the apoptotic index, mitotic index, and turnover index in premalignant and malignant squamous cell lesion of the oral cavity: How much is their diagnostic and prognostic role?. J Sci Soc 2019;46:49-52

How to cite this URL:
Singh P, Kumar V, Singh G, Singh A, Singh A. Significance of the apoptotic index, mitotic index, and turnover index in premalignant and malignant squamous cell lesion of the oral cavity: How much is their diagnostic and prognostic role?. J Sci Soc [serial online] 2019 [cited 2023 Mar 27];46:49-52. Available from: https://www.jscisociety.com/text.asp?2019/46/2/49/276978

Introduction

Carcinoma of the oral cavity is one of the most common cancers in our country today. It is the most frequent cancer in males and second most common in females.^[1] Squamous cell carcinoma is usually preceded by premalignant lesions. Early diagnosis of these lesions increases the chances of cure in patients. The biological behavior of the tumor depends both on the proliferative activity and on apoptosis. Proliferative activity of a tumor depends on the stimulation of growth signals from oncogenes and inactivation of tumor-suppressor genes.^[2] Apoptosis is recognized as a physiological mechanism for controlling cell numbers, and its subversion is thought to contribute to carcinogenesis. The tendency of a tumor cell to undergo apoptosis has an important role in tumor progression and response to the treatment.^[3] Mitosis is a process wherein a mother cell divides exactly into two daughter cells. The various phases of mitosis include prophase, metaphase, anaphase, and telophase. Defects of mitosis result in various nuclear abnormalities, namely micronuclei, nucleation, broken egg appearance, pyknotic nuclei, and increased number of and/or abnormal mitotic figures. These abnormal mitotic figures are commonly observed in oral epithelial dysplasia and squamous cell carcinoma. Increased number of and/or abnormal mitotic figures are important criteria that carry increased weightage in the grading of dysplasia.^[4] Several techniques are used to measure cell proliferation and apoptosis. By measuring these parameters, the progression and prognosis of a tumor can be evaluated. Proliferative activity of a tumor can be assessed by measuring the mitotic index (MI) while apoptosis by counting apoptotic bodies.

Materials and Methods

This study was a prospective study comprised 68 histologically proven cases of premalignant and malignant squamous cell lesions of the oral cavity reported in the department of pathology of our hospital. The study was conducted over a period of 1 year. Immmunocompromised patients and recurrence of previously treated cases were excluded from the study. Biopsy specimens were fixed in 10% formalin, dehydrated in ascending grades of alcohol, cleared in xylene and embedded in paraffin. Sections of 2–3 μm thickness were stained with hematoxylin and eosin. Detailed histopathological examination was carried out. Premalignant lesions were mild dysplasia, moderate dysplasia, and severe dysplasia. Malignant group of lesions included were well-differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (MDSCC), and poorly differentiated squamous cell carcinoma (PDSCC). Apoptotic cells were identified by cell shrinkage, condensation, and deep eosinophilia of the cytoplasm and pyknotic, round-to-oval nucleus. Apoptotic index (AI) was calculated as the number of apoptotic cells and apoptotic bodies expressed as the percentage of total number of tumor cells counted in each case. MI was calculated by counting mitosis among 1000 tumor/dysplastic cells. Turnover index (TI) was obtained from the sum of MI and AI, i.e.,

MI + AI = TOI. After calculating these indices, these were correlated with different grades of oral lesions.

Statistical analysis

All the data were analyzed on SPSS version 24 (SPSS Inc., Chicago, USA) programmed. Mann–Whitney test was used for comparing all the three indices between the malignant and premalignant group and also between the subgroups of the malignant group.

Results

The study was conducted on 68 various oral lesions to evaluate the AI, MI, and TI and to correlate these lesions with different grades of oral lesions. Relevant clinical data with reference to age, site of lesion, and history of tobacco chewing were recorded.

Of the 68 cases studied, 61 were male and 7 were female. Major group involved was 40–49 years. Majority of the patients had a history of tobacco chewing [Table 1].

Table 1: Clinical features of squamous cell lesions of the oral cavity

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The most common site involved was the tongue followed by the cheek [Table 2].

Table 2: Frequency of site involved in squamous cell lesion of the oral cavity

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Histologically, cases were grouped as mild, moderate, and severe dysplasia, WDSCC, MDSCC, and PDSCC depending on the degree of differentiation. Mean ± standard deviation value of AI, MI, and TI in various groups is shown in [Table 3].

Table 3: Apoptotic index, mitotic index, and turnover index in the various oral lesions

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For statistical analysis in the premalignant group, a comparison between mild and moderate dysplasia and between moderate and severe dysplasia was made. AI, MI, and TI were calculated. However, both groups show no statistically significant difference (P > 0.05) [Table 4].

Table 4: Mean apoptotic index, mitotic index, and turnover index and various statistical inference in different subgroups of premalignant group

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A comparison between premalignant and malignant group showed a statistically significant difference; also the comparison between well-differentiated and less-differentiated group showed a statistically significant difference (P < 0.05) [Table 5].

Table 5: Mean apoptotic index, mitotic index, and turnover index and statistical inference between premalignant and malignant groups and between well-differentiated and less differentiated subgroups

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Discussion

Squamous cell carcinoma irrespective of the site evolves through a sequence of changes occurring in the normal squamous epithelium, ranging from dysplasia of varying degrees to frank malignancy.^[4] Individuals with primary dysplastic lesions in the oral cavity are at risk for developing oral squamous cell carcinoma.^[5] Various stimuli can induce apoptosis which by various signaling pathways cause activation of the apoptotic machinery. Increased and abnormal mitosis indicates genetic damage. This is an important feature seen in precancerous lesions and cancer. Thus, identification and quantification of mitosis form an indivisible part of the histological grading systems used for the prognostication of precancerous and cancerous lesions.^[4] Apoptosis and cellular proliferation have been known to play an important role in tumor progression and development. In our study, we evaluated 68 cases of various oral lesions for AI, MI, and TI and correlated these indices with various grades of oral lesions.

In our study, apoptotic bodies and mitotic figures were counted using the light microscope. AI was seen to increase with an increased grade of dysplasia. The mild and moderate dysplasia of oral cavity is shown in [Figure 1] while the severe dysplasia and squamous cell carcinoma is displayed in [Figure 2]. An increase of AI was noted with increasing degree of dysplasia with a peak value in WDSCC, which showed that apoptosis increased with disease progression but decreased with loss of differentiation of the tumor.^{[6],[7],[8],[9],[10]}

Figure 1: Microphotography shows mild (left) and moderate (right) dysplasia oral cavity (H and E, ×400)

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Figure 2: Microphotography shows severe dysplasia (left) and squamous cell carcinoma (right) oral cavity (H and E, ×400)

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In our study, comparison between the mean AI, mean MI, and TI in the premalignant versus malignant group showed a statistically significant difference. Comparison between mild versus moderate dysplasia as well as moderate versus severe dysplasia was statistically insignificant. A comparison between well-differentiated and less-differentiated groups showed a statistically significant difference. This finding suggests how the histological behavior of the lesion suddenly changes as they cross the line from premalignant to malignant type. This also reestablished the fact that these highly proliferative lesions also have a high rate of cell turnover. Besides these, proliferative and apoptotic indices have also been found to be useful to distinguish between benign and malignant lesions of the oral cavity.

Conclusion

AI-, MI-, and TI-based parameter can be performed by simple light microscope and can provide useful information and predict the behavior of the lesion. A combination of MI screening with proliferation and apoptotic assay is more compeling and comprehensive give more conclusion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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