Myanmar Health Sciences Research Journal
Original Articles :
Myanamr Health Research Registration 2022; 34(1-3): 26-32.
DOI:

Immunoexpression of p16INK4a and Ki- 67 Patterns on Cell Blocks to Identify Significant Preneoplastic Cervical Lesions

Nan Cho Nwe Mon*, Aye Aye Lwin, Ohn Mar Kyaw, May Thazin Hlaing & Kyaw Soe

Myanmar Health Sciences Research Journal, Vol. 34, No. 1-3, 2022

ABSTRACT

Cervical cancer can be prevented by regular screening. The widely used primary screening test is Pap cytology but it has low single test sensitivity and may generate equivocal results. Therefore, new biomarkers are particularly attractive tests that can be used to specifically identify at one visit. The study was aimed to detect the expression of p16INK4a and Ki-67 patterns on cell blocks to identify significant preneoplastic cervical
lesions for detection of cervical cancer. A retrospective cross-sectional descriptive study was carried out in HIV infected women attending Antiretroviral Therapy Clinic, Insein General Hospital from July, 2018 to September, 2019. The 50 residual samples of abnormal cervical cytology were recruited. These samples included (38/50) of Atypical Squamous Cell of Undetermined Significance (ASCUS), (6/50) of Low Grade Squamous Intraepithelial Lesion (LSIL), (3/50) of High Grade Squamous Intraepithelial lesion (HSIL), (2/50) of Atypical Squamous Cell but cannot exclude HSIL (ASC-H) and (1/50) of Atypical Glandular Cell (AGC). Their mean age was (33; ±7 years). Cell blocks were prepared from residual cellular sediments of samples. Then, they were stained with H& E and with p16INK4a and Ki-67 immunostaining. In 60% (30/50 cases), the diagnosis made on using cell block were abnormal cervical lesions which were agreement with previous Pap cytology diagnosis (p<0.001). According to previous Pap cytology diagnosis, 8% (3/38) of ASCUS, 33% (2/6) of LSIL and 66% (2/3) of HSIL were p16 INK4a and Ki-67 positive. According to cytomorphologic diagnosis on cell block, 13% (3/24) of ASCUS, 50% (2/4) of LSIL and 100% (2/2) of HSIL were p16 INK4a and Ki-67 positive. The immunoexpression of p16 INK4a and Ki-67 exhibited
a statistically significant association (p<0.001) with the presence of significant pre-neoplastic lesions on cell block. Therefore, this immuno-expression is useful to find out early diagnosis of cancer especially in HSIL/Cervical Intraepithelial Neoplasia (CIN2+). This study high-lighted the use of p16INK4a and Ki-67 on cell block preparation enhances ability to distinguish high grade lesions from less significant conditions in diagnostic ambiguity. The application of this immunostaining will reduce the unnecessary referral for colposcopy and tissue biopsy as well as over and under diagnosis in cytology screening.


RESULT
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INTRODUCTION
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Cervical cancer exists as a continuing major public health concern in middle-aged women, particularly in resource poor countries. This cancer was the fourth most common cancer in women ranking after breast cancer, colorectal cancer and lung cancer.1 The long term


SUPPLEMENTARY MATERIAL
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A retrospective cross-sectional descriptive study was carried out from July, 2018 to September, 2019. After getting informed consent, HIV infected women who were attending Antiretroviral Therapy Clinic, Insein General Hospital has been chosen for the study. Their age range was between 18-48 years. Pap smear samples were collected by using cytobrush and stored in -20°C for long-term storage. The 50 residual samples of abnormal cervical cytology were involved in the study.


DISCUSSION
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p16 INK4a and Ki-67 is a surrogate marker of human papilloma virus infection and cell proliferation, respectively. Over expression of p16INK4a can be used as a biomarker for precancerous and cancerous cervical lesions. Ki-67 can be detected within the nucleus of proliferating cells.

Out of 50 cases, 30 cases (60%) of cell block diagnosis were abnormal cervical lesions which were agreed with previous Pap cytology diagnosis in this study. In one of
 the study, 73% (62/85 cases) of the diagnosis made using cell blocks were in agreement with the cytology diagnosis.8


ACKNOWLEDGMENT
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The Authors would like to express our greatest thanks to Department of Medical Research for permission to conduct the study and for supporting the grant to this study. We would like to aslo thanks to Dr. Mon Mon Aung, Dr. Ne Myo Aung and Dr. Mar Mar Kyi (Insein General Hospital) for their kind support. The authors greatly acknowledge the patients who participated in this study.

 


CONFLICT OF INTEREST
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REFERENCES
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2.       Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Annals of Internal Medicine 2000; 132(10): 810-819.

3.       Schiffman M, Wentzensen N, Wacholder S, Kinney W, Gage JC, & Castle PE. Human papillomavirus testing in the prevention of cervical cancer. Journal of the National Cancer Institute 2011; 103(5): 368-383.

4.       Tay TKY, Lim KL, Hilmy MH, Thike AA, Goh ST, Song LH, et al. Comparison of the sensitivity and specificity of p16/Ki-67 dual staining and HPV DNA testing of abnormal cervical cytology in the detection of histology proven cervical intraepithelial neoplasia grade 2 and above (CIN 2+). The Malays Journal of Pathology 2017; 39(3): 257-265.

5.       Yu LL, Chen W, Lei XQ, Qin Y, Wu ZN, Pan QJ, et al. Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China. Oncotarget 2016; 7(16): 21181-21189.