|LETTER TO THE EDITOR
|Ahead of print publication
Human epidermal growth factor receptor 2 is frequently over-expressed in gastric carcinoma in north Indian patients
Pragya Jain1, Tanvi Arora2, Neelam Wadhwa2, Mohit Kumar Joshi3
1 Department of Pathology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
2 Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India
3 Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this URL:|
Jain P, Arora T, Wadhwa N, Joshi MK. Human epidermal growth factor receptor 2 is frequently over-expressed in gastric carcinoma in north Indian patients. J Can Res Ther [Epub ahead of print] [cited 2019 Dec 7]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=263858
We read with interest the recently published work of Xu et al. on the expression of human epidermal growth factor receptor 2 (HER2) and other markers in Chinese patients of gastric carcinoma (GC). In this context, we would like to share our experience of HER2 overexpression in north Indian patients of GC. HER2 overexpression is an important molecular mechanism in gastric carcinogenesis. HER2-targeted molecular therapy is thus well-suited option for advanced cases of GC, where surgical intervention is precluded. Accurate determination of HER2 expression status in GC is crucial.
The distribution of GC in India is markedly heterogeneous; the high incidence is known in North-East India and Kashmir. In plains of north India, it is uncommon cancer and does not figure in top 10 cancer sites. Moreover, meager data are available on HER2 expression in GC from this region.
We evaluated HER2 expression by immunohistochemistry (IHC) in 50 histologically confirmed GC in north Indian patients (January 2010–March 2015) using the modified criteria proposed by Hofmann et al. Cases with 2+/equivocal IHC results were subjected to dual color fluorescent in-situ hybridization; HER2/centromere ratio ≥2.0 was considered amplified. Institutional Ethical Committee Clearance was obtained before the commencement of the study.
Thirty-three (66%) cases showed HER2 overexpression, which is comparable to 69% of frequency reported by Xu et al. However, this proportion is higher than most reports from several parts of the world, including India. In a meta-analysis derived from 42 studies across several continents, Jørgensen and Hersom reported a wide range of HER2 positivity (4.4%–53.4%). The previously reported frequency of HER2 positivity in GC from other parts of India varies between 18.7% and 44.2%. Possible reasons for such a wide range of variation could include genetic susceptibility, environmental factors involved in etiopathogenesis of GC, and analytical factors of detection.
The proportion of 2+/equivocal cases with HER2 gene amplification was 17.6%. This is comparable to 26% in the Trastuzumab for Gastric Cancer (ToGA) trial. The HER2 positivity rate in biopsies was comparable to the resection specimens. This is clinically relevant considering that biopsies are often the only available tissue. Similar to Xu et al., we found no correlation of HER2 with demographic factors. Unlike them, we did not find correlation between HER2 and conventional pathologic parameters. The heterogeneity in HER2 association with prognostic factors is noted in the world literature and sets it different from its consistent association with breast cancer. We also found dysplastic glands to express HER2, implying its role in the development of GC.
The ToGA trial has established the role of targeted molecular therapy against HER2 in patients with advanced gastric/gastroesophageal carcinoma. Hence, accurate assessment of HER2 expression by IHC and if required, followed by in situ hybridization has become an integral part of workup of GC patients. We found HER2 overexpression to be a frequent event in north Indian patients of GC, identifying patients who would potentially benefit from targeted molecular therapy. Biopsies are suitable for determination of HER2 expression. HER2 plays an important role in gastric carcinogenesis.
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Conflicts of interes
There are no conflicts of interest.
| > References|| |
Xu W, FU J, Wu H. Human epidermal growth factor receptor 2 expressions and Janu-activated kinase/signal transducer and activator of transcription 3-suppressor of cytokine signalling 3 pathway may be associated with clinic-pathological features and prognosis of gastric cancer. J Can Res Ther 2018;14:311-8.
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Jørgensen JT, Hersom M. HER2 as a prognostic marker in gastric cancer – A systematic analysis of data from the literature. J Cancer 2012;3:137-44.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al.
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-97.
Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al.
Assessment of a HER2 scoring system for gastric cancer: Results from a validation study. Histopathology 2008;52:797-805.