Abstract
Background: Cervical cancer is the most common cancer in women worldwide with current knowledge showing rising trends of adenocarcinoma over Squamous cell carcinoma. They are more aggressive with relatively worse prognosis. Thus, to improve the overall disease free duration, a novel diagnostic and therapeutic immunomarker is required. The present study aims to evaluate the significance of p16 and HER-2/neu expression in patients of adenocarcinoma cervix.
Material and Methods: A Prospective study on 33 cases of adenocarcinoma cervix diagnosed on resected specimens as well as core biopsies was conducted from January 2019 to December 2019. All relevant clinical data was retrieved from Institute’s electronic medical record system. Histopathological examination and Immunohistochemistry using p16 and HER-2/neu antibodies were performed on all formalin fixed paraffin embedded tissues.
Results: A total of 33 cases of adenocarcinoma cervix were observed in the present study. Positive p16 expression with variable intensity was noted in all the cases. HER-2/neu was strongly expressed in only 4 cases (12%) of Adenocarcinoma cervix. However, positivity was associated with all cases showing parametrial extension and all these cases were histologically diagnosed as high grade. Although statistically significant correlation between HER-2/neu expression, stage of tumor, presence of lympho-vascular invasion and nodal metastasis could not be established but cases with high grade of the tumor and parametrial extension did show strong immunoreactivity with HER-2/neu oncoprotein.
Conclusion: To conclude, p16 positivity was observed in all cases of adenocarcinoma cervix but role of Her2/neu is still debatable and needs further studies with larger sample size to establish its significance.
Keywords: Adenocarcinoma cervix; p16; HER-2/neu; Prognosis.
References
- Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health.2020; 8(2):e191-e203.
- Ueda A, Takasawa A, Akimoto T, Takasawa K, Aoyama T, Ino Y, et al. Prognostic significance of the co-expression of EGFR and HER2 in adenocarcinoma of the uterine cervix. PLoS ONE 2017;12(8): e0184123.
- Pirog EC, Lloveras B, Molijn A, Tous S, Guimerà N, Alejo M, et al. HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases. Mod Pathol.2014 Dec; 27(12):1559-67.
- Holl K, Nowakowski AM, Powell N, et al. Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias: results from a European multinational epidemiological study. Int J Cancer. 2015; 137(12):2858–2868.
- Kleter B, van Doorn LJ, Schrauwen L, et al. Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol. 1999; 37(8):2508–2517.
- Tringler B, Gup CJ, Singh M, et al. Evaluation of p16INK4a and pRb expression in cervical squamous and glandular neoplasia. Hum Pathol. 2004; 35:689–696.
- Gupta N, Singh S, Marwah N, Kumar S, Chabra S, Sen R. HER-2/neu expression in lesions of uterine cervix: is it reliable and consistent? Indian J Pathol Microbiol. 2009; 52(4):482-85.
- Bruni L, Albero G, Serrano B, Mena M, Gómez D, Munoz J, et al. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report 17 June 2019.
- Bodner K, Laubichler P, Kimberger O, Czerwenka K, Zeillinger R, Bodner-Adler B. Expression of p16 protein and epidermal growth factor receptor in patients with adenocarcinoma of the uterine cervix: an immunohistochemical analysis. Arch Gynecol Obstet. 2011;283: 611–616.
- Ueda A, Takasawa A, Akimoto T,Takasawa K, Aoyama T, Ino Y, et al. Prognostic significance of the co-expression of EGFR and HER2 in adenocarcinoma of the uterine cervix. PLoS ONE 2017; 12(8): e0184123.
- Aziz N, Yousfani S. Pattern of presentation of cervical carcinoma at Nuclear Institute of Medicine and Radiotherapy, Pakistan. Pak JMed Sci 2013; 29(3):814-817.
- Young RH, Scully RE. Villoglandular papillary adenocarcinoma of the uterine cervix: a clinicopathologic analysis of 13 cases. Cancer 1989; 63(9):1773–1779.
- Nargesh Izadi-Mood, Kourosh Asadi, Hadi Shojaei. Potential diagnostic value of p16 in premalignant and malignant cervical lesions. J Res Med Sci. 2012; 17(5);428-433.
- Lu X, Toki T, Konishi I, Nikaido T, Fujii S. Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix. A possible marker of a favourable prognosis. Cancer 1988; 82(12):2409–2417.
- Sarwade Pramod, PatilSunita, BinduRajan. Immunohistochemistry study for HER-2/neu expression in lesions of uterine cervix. Int J Cur Res Rev 2016; 8(13):50-57.
- Joseph T and Raghuveer CV. HER-2/neu expression in cervical intraepithelial neoplasia and cervical carcinoma. International Journal of Biomedical and Advance Research 2015; 6(01):47- 52
- Sharma N, Kaushik A, Sumanashree, Sharma U. Evaluation of Her-2 neu Over Expression in Morphological Variants of Cervical Carcinoma, 2016;3(2):A207-A213.
- Mandai M, Konishi I, Koshiyama M, Komatsu T, Yamamoto S, Nanbu K, et al. Altered expression of nm23-H1 and c-erb B-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix. Cancer 1995;75:2523-9.
Corresponding Author
Dr Prakriti Shukla
Assistant Professor, Department of Pathology, Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh, India