Clinicopathological, morphological and ki-67 proliferative index in oral squamous cell carcinoma in a tertiary care teaching hospital

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Author Details : Garima Sharma, Neil Sharma*, Narayani Joshi, B P Nag

Volume : 4, Issue : 1, Year : 2019

Article Page : 1-8

https://doi.org/10.18231/2581-3706.2019.0001

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Abstract

Abstract

Introduction: Oral cancers are neoplasms which are malignant and affect the structures or tissues of the mouth. These malignant neoplasms can begin as lesion which is primary or can be from a distant site which can be metastatic. It can also be an extension of some adjacent tumoural area.^[1]In developing countries, oral cancer is one of the most important cause of morbidity and mortality. Oral cancer is sixth most common cancer worldwide, ranking eighth in developed countries and third in the developing world.^[2] A higher incidence is reported in Southeast Asia. Of all the cancers in the Indian subcontinent, this carcinoma accounts for almost 40%.^[3]

Aims: To study clinicopathological, morphological and ki-67 proliferative index in oral squamous cell carcinoma.

Materials and Methods: This study is carried out in Department of Pathology, Mahatma Gandhi Medical college and Hospital, Sitapura, Jaipur, Rajasthan from 1 June 2015 to 31^st May 2017. Institutional ethical committee approval was obtained prior to study.Informed consent was obtained from the patients before enrolment into the study.

Statistical methods: sensitivity, positive predictive value, negative predictive value, and specificity was calculated. The study was a Hospital based observational study.

Results: A total of 50 histologically diagnosed cases of “oscc”, with clinicopathological parameters and Immunohistochemical marker comprising of Ki-67 was studied. Out of non-invading 12 cases, 9(18%) had “Ki-67 Labeling Index” as high and 3 cases (6%) showed low labeling index.Out of 34(68%) high grade cases, in 29 cases (58%), Ki-67 expression was high and 5 cases (10%) had low expression. Also, out of remaining 16(32%) low grade cases, 7 cases (14%) showed high expression of Ki-67 and 9 cases (18%) showed low expression and show statistically significant p value.

Conclusion: Oral squamous cell carcinoma is significantly associated with elderly age group and with male sex.Ki-67 expression was statistically significant when compared with histological differentiation. This indicates that Ki-67 staining may be of use in individual tumor diagnosis and prognosis. In the histopathological assessment of the severity of oral squamous cell carcinoma, Ki-67 marker proves to be a clinically useful supplement.

Hence we propose that Ki-67 is a useful marker of proliferation. It can be used for the diagnosis of oral epithelial dyspalasias which have tendency to undergo malignant transformation

Keywords: Ki-67, Oral squamous cell carcinoma, Histology.

Introduction

Aims and Objectives

In histological grading, 16 cases (32%) with well differentiated squamous cell carcinoma, 7(14%) had high Ki-67 proliferative index and 9 cases (18%) had low Ki-67 proliferative index. Out of 31 cases (62%) of moderately differentiated squamous cell carcinoma, 26 cases (52%) show high Ki-67 and only 5 cases (10%) had low Ki-67 LI.
Only 3 cases (6%) were poorly differentiated and had high
Ki-67 LI. The relationship of Ki-67 expression was statistically significant when compared with histological grading. (p value=0. 0121).

Out of 50 cases of oral squamous cell carcinoma, maximum cases presented with ulcerative growth (46 cases)
in which maximum cases were diagnosed as moderately differentiated squamous cell carcinoma.

On distributing the patients on the basis of clinical features, mostly patients presented with a complaint of both
dysphagia and hoarseness who were diagnosed as moderately differentiated squamous cell carcinoma

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Fig. 1: A nodular and ulcerated lesion of OSCC on Floor of Mouth and Tongue

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Fig. 2: Ki-67 immunopositivity in MDSCC (moderately differentiated squamous cell carcinoma) of Tongue (H & E,400x)

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Fig. 3: Ki-67 poistive PDSCC(poorly differentiated squamous cell carcinoma) of Buccal Mucosa (H & E,400x)

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Fig. 4: Poorly differentiated squamous cell carcinoma of Buccal Mucosa (H&E 100x)

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Fig. 5: Poorly differentiated squamous cell carcinoma of Tongue (H&E 100x)

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Fig. 6: Poorly differentiated squamous cell carcinoma of Buccal Mucosa (H&E 100x)

Discussion

This study entitled “Clinicopathological, morphological and Ki-67 proliferative index in oral squamous cell carcinoma in a tertiary care teaching hospital” was done in the Department of Pathology, Mahatma Gandhi Medical College, Jaipur during the year 2015-2017 on the 50 cases. Although the lesions are easily accessible for clinical examination, their prognosis can be difficult to assess in the context to location variability, risk factors, histopathological and molecular aspects involved in their appearance and progression. Present study comprises of 50 cases of oral squamous cell carcinoma diagnosed on histopathology.

The aims of this study is assessing the Ki-67 marker and to correlate other prognostic factors such as age, sex, social habit, histological staging and histological grading with expression of these markers.

Distribution of Age Group

In the present study, the mean age of the patients of oral squamous cell carcinoma was 51±15. 5 years and range from 20 to 79 years. The patients was maximally distributed in the 40-69 years (66%) age group.

Sharmistha M Patel et al (2014)^[9] observed the mean age of oral squamous cell carcinoma cases was 49±12. This was in accordance to our study.

Abhay R. Chandak et al (2011)^[29] observed the mean age of oral squamous cell carcinoma cases was 53. 20 years.

According to a study conducted by Sieczka E et al (2011),^[30] the mean age of presentation of oral cancer is 75 years ranging in age from 34 to 94 years in Asian population.

Distribution According to Gender

Our study showed maximum number of cases in male (80%). Female comprised of only 20% of the patient. Thus, the male to female ratio in our study is 4:1.

Males are affected more often than females because of heavier indulgence in both tobacco and alcohol habits in most countries. In India the highest rates of intraoral cancer may be found in women who chew tobacco heavily.^[31]

In a study by Sharma P et al (2010)^[32] on 80 patients of oral squamous cell carcinoma, men were more (68. 7%) than women (31. 2%).

A study by Doshi Neena P et al (2011)^[33]on 80 cases of oral cancer, showed a prevalence of 61. 25% in males. Males were found to be in higher proportion due to high use of tobacco both in the form of chewing and smoking compared to females as the consumption of tobacco and tobacco products was less in the females.

A study carried out by L. P. Dragomir et al (2012)^[34]on 34 oral squamous carcinomas, mostly age of patients was from 20-40 years (61. 8%), males being 85. 3% and smokers and/or alcohol consumers being 85. 3%.

In 80 cases of oral cancer, Khandelkar et al (2006)^[35] studied that prevalence of cancer in males was 61. 25%. Males were found to be in higher proportion due to high use of tobacco both in the form of chewing and smoking compared to females as the consumption of tobacco and tobacco products was less in the females.

Distribution of Patients According to Social Habit and Anatomical Site

In our study group, maximum number (%) of patients chewed tobacco and smoked (48%), followed by combined habit of smoking and alcohol (14%). Tongue was the most commonest of cancer (52%) followed by buccal mucosa (30%).

This is in concordance with the study done by Sharmistha M Patel et al (2014)^[9] on 39 cases who found that tongue was the commonest site of oral cancer followed by buccal mucosa.

In the study on 57 cases of oral cancer, Marcelo Gadelha Vasconcelos et al (2014)^[36]found that the most common site of squamous cell carcinoma was tongue. The most frequent habit was combination of smoking and alcohol (42.1%), smoking alone was followed by it. (31.6%).

Muhammad Kashif et al (2015)^[1] observed that in oral cavity, the most commonly involved site was tongue (mostly lateral border of tongue) (46%) followed by patients present with tumour on Buccal mucosa (6%). Also high proportion of patients with OSCC were habitual smokers and had a habit of pan chewing.

Halboub et al (2012)^[37]also identified floor of mouth, tongue as the most common sites of oral cancer. Smoking (96.3%) and smokeless tobacco (91.8%) were identified as the major risk factors among various risk factors for causing oral cancer.

Whereas the study conducted by Tahir et al (2013)^[38]is in contrast with the present study which reported that Buccal mucosa was the most common site of involvement which was seen predominantly in (32.4%) cases.

Also, the study conducted by Nemes et al (2008)^[39]in Hungary reported that the floor of mouth was the most common site of involvement in OSCC patients.

Distribution According to Histological Grading

In the present study, Out of 50 cases of squamous cell carcinoma, maximum number of cases (62%) were moderately differentiated followed by well differentiated (32%). Only few cases (6%) were of poorly differentiated OSCC.

As considering the histological grading of OSCC, the study conducted Jerjes et al (2010)^[40]stated that half of the patients were presented with MDSCC which is favour of with the present study.

 “Well and moderately differentiated SCC” were the most common histological grade of oral SCC in young patient reported by Iype et al (2000)^[41]and Iamaroon et al (2004).^[42]On the other hand, in studies carried out by Effiom (2008),^[43] poorly differentiated SCC was the most common grade of oral SCC.

Comparison between Gender and Histological Grade of OSCC

Chi-square test was applied to study the relation between gender and histological grade of OSCC and it was found statistically insignificant.

This is in accordance with study done by Muhammad Kashif et al (2015)^[1]who observed, out of 127 patients mostly well differentiated and moderately differentiated tumours were seen (44.9%) whereas only few (10.2%) were poorly differentiated. Relation of gender and histological grade of OSCC was statistically insignificant.

Correlation of Ki-67 Expression and Histological Grade

Ki-67 marker is tested in all 50 cases. Out of total 50 cases, 36 cases (72%) were found to have high proliferation for Ki-67 and only 14 cases (28%) were found to have low proliferation.

In histological grading, the low grade (well differentiated) were 16 cases (32%), and high grade were 34 cases (68%) (moderately and poorly differentiated). Out of 34 (68%) high grade cases, 29 cases (58%) had high Ki-67 expression and 5 cases (10%) had low levels. Also out of remaining 16 (32%) low grade cases, 7 cases (14%) had high expression of Ki-67 and 9 cases(18%) had low levels.

In our study, the immuno expression of Ki-67 was seen in all 50 cases of OSCC. The relationship of Ki-67 expression was statistically significant when compared with histological grading (p value=0. 0121).

On a study of 35 patients with intraepithelial lesions and SCC, Intisar Salim et al(^[44]), observed an increase in over expression of Ki-67 with increase in grade of histopathologic abnormalities in oral IEL and SCC. Ki-67 LI of highest level belonged to poorly differentiated SCC (87. 7%) and high grades IEL (80%).

Rakheja Mahima et al (2015)^[45]in 105 cases showed closely similar results. A highly significant correlation was found between the expression of Ki-67 and grades of OSCC (p<0>

Abhay R. Chandak et al (2011)^[9]studied that Ki-67 LI showed a significant increase from well differentiated to moderately differentiated OSCC.

A significant correlation was observed by Carlos de Vicente et al (2002)^[46] observed between the histological grading and Ki-67 labelling index.

Kannan et al (1996),^[47] and Premlatha et al (2010)^[48] observed that on statistical analysis (with chi-square test), a highly significant correlation was observed between the advancing grades of oral squamous cell carcinoma and expression of Ki-67. (p<0>

According to Kurokawa et al^[49]Ki-67 over expression on tumour borders, is associated to its histological grade (p<0>^[50] did not find any significant correlation of Ki-67 positivity when compared with histological differentiation.

While Piattelli et al (2002)^[51] could not show significant differences among different grades of OSCC.

Correlation of Ki-67 Expression and “TNM” staging

Our study did not show significant correlation of Ki-67 expression with TNM staging.

This is in accordance with study done by A. R. Chandak et al (2011)^[9] on 50 cases of oral squamous cell carcinoma whose results also showed no significant correlation of Ki-67 LI with TNM staging.

Conclusion

Oral squamous cell carcinoma is significantly associated with elderly age group and with male sex. Commonest site being buccal mucosa and is most commonly associated with combined habit of smoking and tobacco chewing.Higher expression of Ki-67 was seen which was statistically significant when compared with histological differentiation. This highlights the importance of Ki-67 in squamous cell carcinoma. In the histopathological assessment Ki-67 helps supplement the clinical data.

Hence we propose that Ki-67 is a useful marker of proliferation. It can predict the transition of oral epithelial dysplasia to malignancy.

Conflict of Interest: None.

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How to cite : Sharma G, Sharma N, Joshi N, Nag B P, Clinicopathological, morphological and ki-67 proliferative index in oral squamous cell carcinoma in a tertiary care teaching hospital. IP J Diagn Pathol Oncol 2019;4(1):1-8

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