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Human Epidermal Growth Factor Receptor-2 in Sri Lankan Gastric Carcinoma Patients with Clinicopathological Association and Survival

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Abstract

Background

HER2 protein expression indicates adverse prognosis in gastric adenocarcinoma (GCa). GCa HER2 positivity ranges from 10 to 22.8%. Similar data are scarce in South Asia and unavailable in Sri Lanka.

Aim

To evaluate HER2 protein expression, its clinicopathological relationship and survival in a Sri Lankan GCa cohort.

Methods

One hundred consecutive GCa patients were recruited prospectively for 2 years. Histological diagnosis was confirmed on endoscopic biopsies/gastrectomy specimens. Clinicopathological and overall survival data were collected. HER2 expression was assessed using immunohistochemistry. 2+ and 3+ scores were considered positive. HER2 expression and clinicopathological parameters were analyzed by Chi-squared test and multivariate analysis with logistic regression using SPSS-21. Kaplan–Meier method and log-rank test were used for survival analysis.

Results

Study includes 56 biopsies and 44 resections. Male/female ratio was 1.9:1. Mean age of diagnosis was 61.1 years (range 32–82). Majority tumors were proximally located (58%). HER2 positivity was 9%. Even though intestinal subtype predominated HER2 positivity was mostly among diffuse variant (14.8%). In multivariate analysis, mitotic count >5/hpf, high nuclear grade and tumor necrosis were significantly associated with HER2 positivity, while poor differentiation, signet cells, extracellular mucin, perineural invasion and pathological nodal metastasis (all p < 0.05) showed a correlation in univariate analysis. Mean follow-up duration was 37.4 weeks (range 0–104). HER2 positivity was associated with a significantly lower median overall survival (p = 0.046).

Conclusion

GCa HER2 positivity was 9%, associated with a lower median overall survival. Adverse histological features had a positive correlation with HER2 positivity. These histological features could direct patients for confirmatory HER2 testing in limited resource settings.

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Abbreviations

HER-2:

Human epidermal growth factor receptor

GCa:

Gastric adenocarcinoma

CECT:

Contrast enhance tomography

IHC:

Immunohistochemistry

HPF:

High-power field

CEP:

Centromeric probe

FISH:

Fluorescence in situ hybridization

SISH:

Silver in situ hybridization

GOJ:

Gastroesophageal junctional

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Acknowledgments

The authors wish to thank Dr. Gayani Ranaweera for contributing toward the literature survey and proposal writing for funding and Mrs. G. K. Wijesinghe (Staff technical officer) for technical assistance for the laboratory work. Authors wish to acknowledge The National Research Council, Sri Lanka, for funding this study. The Authors wish to thank Dr. Medhavini Dissanayake and Dr. Sameera Ravishan who helped in data collection and Dr. P. K. B. Mahesh for assistance rendered for statistical analysis.

Funding

The National Research Council of Sri Lanka.

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Authors and Affiliations

  1. University Surgical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka

    Duminda Subasinghe, Sivasuriya Sivaganesh & Dharmabandhu Nandadeva Samarasekera

  2. Department of Pathology, National Hospital of Sri Lanka, Colombo, Sri Lanka

    Ananthi Samarsekera

  3. PathWest Laboratory Medicine, Perth, Australia

    Mariyan Priyanthi Kumarasinghe

  4. School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia

    Mariyan Priyanthi Kumarasinghe

  5. Department of Pathology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka

    Menaka Dilani Samarwickrema Lokuhetty

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  1. Duminda Subasinghe
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  4. Mariyan Priyanthi Kumarasinghe
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  5. Dharmabandhu Nandadeva Samarasekera
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Contributions

MDSL designed the study with contributions from MPK, SS, AS and DNS. DS was involved in laboratory work, data collection, analysis and writing the manuscript. MDSL critically evaluated and edited the manuscript with SS and MPK. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Duminda Subasinghe.

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The data will not be made available in order to protect the participant’s identity.

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Authors declare that they have no conflict of interests.

Ethics approval and consent to participate

This study was conducted according to the principles expressed in the Declaration of Helsinki and approved by the Ethics review committee of Faculty of Medicine, University of Colombo and The National hospital of Sri Lanka.

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Subasinghe, D., Sivaganesh, S., Samarsekera, A. et al. Human Epidermal Growth Factor Receptor-2 in Sri Lankan Gastric Carcinoma Patients with Clinicopathological Association and Survival. Dig Dis Sci 62, 2498–2510 (2017). https://doi.org/10.1007/s10620-017-4647-2

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  • DOI: https://doi.org/10.1007/s10620-017-4647-2

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