Immunohistochemical expression of p16INK4a in premalignant lesions and malignant tumours of cervix

Authors

  • Parminder J. S. Sandhu Department of Pathology, GGS Medical College, Faridkot, Punjab, India
  • Sarita Nibhoria Department of Pathology, GGS Medical College, Faridkot, Punjab, India
  • Vaneet K. Sandhu Department of Pathology, GGS Medical College, Faridkot, Punjab, India
  • Harpreet Kaur Department of Obstetrics and Gynaecology, GGS Medical College, Faridkot, Punjab, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20231561

Keywords:

p16INK4a, Cervical carcinoma, IHC, CIN, HSIL, LSIL

Abstract

Background: Cervical carcinoma is the third most common cancer in women worldwide and firth most common cause of cancer related deaths. Human Papilloma virus, the most common cause of cervical cancer, causes functional inactivation of pRb, resulting in overexpression of p16INK4a. The overexpression of p16INK4a correlates well with the degree of cervical dysplasia and neoplasia. The present study is done to determine the IHC expression of p16INK4a so that it may be used as a biomarker for HPV and may play a role in the prevention, diagnosis and prognosis of cervical neoplasm.

Methods: The present study was conducted on 60 formalin-fixed, paraffin-embedded specimens of cervical neoplasms, which comprised 47 cases of squamous cell carcinoma followed by 8 cases of adenocarcinoma, 3 cases of HSIL and 2 cases of LSIL. These were then subjected to IHC by p16INK4a. Cytoplasmic and nuclear positivity for p16INK4a was noted.

Results: Overall 95% cases were positive for p16INK4a expression, 100% cases of adenocarcinoma, 98% cases of squamous cell carcinoma, 100% cases of HSIL and 0% cases of LSIL were positive for p16 expression.

Conclusions: The present study showed statistical correlation of immunoreactivity of p16INK4a with histological type was clinically significant (p value <0.0001). In our study, p16INK4a immunohistochemical expression increased with increasing degree of dysplasia and with presence of cervical carcinoma.

References

Sarwath H, Bansal D, Husain NE, Muhamed M, Sultan AA, Bedri S. Introduction of p16INK4a, as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan. Infect Agents Cancer. 2017;12:50-4.

Esmaeili HA, Pourlak T, Ghamari B, Shayan FK, Sanaat Z, Soltani GG, et al. Comparison of nuclear P16 immunostaining in atypical and normal endocervical glands: A descriptive analytical study. J Anal Res Clin Med. 2018;6:66-71.

Jacob AA, Sundaram A. P16, Ki67 and P63 staining pattern in squamous metaplasia, CIN and cervical cancer. Int J Res Med Sci. 2018;6:882-8.

Ellenson LH, Pirog EC. The female genital tract. In: Kumar V, Abbas AK, Aster JC, editors. Robbins and Cotran pathologic basis of disease. 10th ed. India: Elsevier. 2020;996-8.

Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U, et al. Overexpression of p16 as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer. 2001;92:276-84.

Murphy N, Ring M, Killalea AG, Uhlmann V, O’Donovan M, Mulcahy F, et al. p16 as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and thin prep smears. J Clin Pathol. 2003;56:56-63.

Cheah PL, Looi LM, Teoh KH, Mun KS, Nazarina AR. p16 is a useful marker of HPV integration allowing risk stratification for cervical malignancies. Asian Pac J Cancer. 2012;13:469-72.

Volgareva G, Zavalishina L, Andreeva Y, Frank G, Krutikova E, Golovina D, et al. p16 as a marker of dysplastic and neoplastic alteration in cervical epithelial cells. BMC Cancer. 2004;4:58-60.

Lesnikova I, Lidang M, Hamilton-Dutoit S, Koch J. p16 as a diagnostic marker of cervical neoplasia: a tissue array study of 796 archival specimens. Diagn Pathol. 2009;4:22-8.

Singh N, Gilks CB, Wong RW, McCluggage WG, Herrington CS. Interpretation of p16 immunohistochemistry in lower anogenital tract neoplasia. BAGP. 2018;1:1-19.

Darragh TM, Colgan TJ, Thomas Cox J, Hellar DS, Henry MR, Luff RD, et al. The Lower Anogential Squamous Terminology Standarization project for HPV-associated lesions: background and consensus recommendations from the college of American Pathologists and the American Society for colposcopy and Cervical Pathology. Int J Gynecol Pathol. 2013;32:76-115.

Stoler MH, Wright TC Jr, Ferenczy A, Ranger-Moore J, Fang Q, Kapadia M, et al. Routine Use of Adjunctive p16 Immunohistochemistry Improves Diagnostic Agreement of Cervical Biopsy Interpretation: Results From the CERTAIN Study. Am J Surg Pathol. 2018;42:1001-9.

Cheah PL, Koh CC, Nazarina AR, Teoh KH, Looi LM. Correlation of p16INK4a immunoexpression and human papilloma virus (HPV) detected by in-situ hybridization in cervical squamous neoplasia. Malys J Pathol. 2016;38:33-8.

Zabin S, Akhtar K, Mohsin Z, Siddiqui SA. Immunohistochemical expression of P16 and Ki-67 in uterine cervical neoplasms. IP J Diagnost Pathol Oncol. 2021;6;194-200.

Izadi-Mood N, Asadi K, Shojaei H, Sarmadi S, Ahmadi SA, Sani S, et al. Potential diagnostic value of p16 expression in premalignant and malignant cervical lesions. J Res Med Sci. 2012;17:428-33.

Kumari K, Vadivelan A. p16INK4A expression in cervical intraepithelial neoplasia and cervical cancer. Original Article Brunei Int Med J. 2013;9:165-71.

Pandey A, Chandra S, Nautiyal R and Shrivastav V. Expression of p16 and hpv 16 with associated risk factors in cervical premalignant and malignant lesions. South Asian J Cancer. 2018;7:236-9.

Srivastava S. P16INK4A and MIB-1: an immunohistochemical expression in preneoplasia and neoplasia of the cervix. Indian J Pathol Microbiol. 2010;53:518-24.

Gupta R, Srinivasan R, Nijhawan R, Suri V, Uppal R. Protein p16INK4a expression in cervical intaepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix. Indian J Pathol Microbiol. 2010;53:7-11.

Kalyani R, Raghuveer CV, Sheela SR. Expression of p16 biomarker in squamous cell carcinoma of uterine cervix and its association with clinicopathological parameters: A cross- sectional study. Biomed Res Ther. 2020;7:3954-6.

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Published

2023-05-26

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Original Research Articles