Expression of PDL1 and Her2neu in Gastric and Gastroesophageal Junction Adenocarcinoma

Animesh Saurabh; Vandana Raphael; Biswajit Dey; Caleb Harris; Vikas Jagtap; Umesh Das

doi:10.1007/s13193-020-01245-w

Expression of PDL1 and Her2neu in Gastric and Gastroesophageal Junction Adenocarcinoma

Indian J Surg Oncol. 2021 Apr;12(Suppl 1):144-151. doi: 10.1007/s13193-020-01245-w. Epub 2020 Oct 16.

Authors

Animesh Saurabh¹, Vandana Raphael¹, Biswajit Dey¹, Caleb Harris², Vikas Jagtap³, Umesh Das⁴

Affiliations

¹ Department of Pathology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, 793018 India.
² Department of Surgical Oncology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, India.
³ Department of Radiation Oncology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, India.
⁴ Department of Medical Oncology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, India.

Abstract

The process of tumorigenesis in gastric carcinoma involves multiple genetic alterations including overexpression of PD-L1, amplification of Her2neu, and mutation of p53. In the present study, the expressions of PD-L1 and Her2neu were analyzed in relation to clinicopathological parameters including p53 in gastric and gastroesophageal junction adenocarcinoma. We examined 100 biopsy and resection samples of gastric and gastroesophageal junction carcinomas for PD-L1, Her2neu, and p53 protein expressions using immunohistochemistry. Scorings were done based on intensity and percentage of tumor cells expressing the markers. Follow-up and survival analyses were done wherever data was available. PD-L1 and Her2neu were seen in 37% and 38% respectively. The analysis showed PD-L1 expression was significantly associated with depth of invasion (p = 0.0007), nodal metastasis (p = 0.0003), and AJCC staging (p = 0.0085). Her2neu negative including equivocal expression was significantly associated with histological grading (p = 0.0043), Lauren classification (p = 0.0042), depth of invasion (p = 0.04), and nodal metastasis (p = 0.017). Combined analysis of PD-L1 and Her2neu showed significant association with histological grading (p = 0.017), Lauren classification (p = 0.005), depth of invasion (p = 0.0035), and nodal metastasis (p = 0.00073). Univariate Cox regression analysis showed that depth of invasion, nodal metastasis, distant metastasis, AJCC staging, and p53 were negative prognostic factors for patients' overall survival. In multivariate analysis, distant metastasis and Her2neu negativity including equivocal cases were independent prognostic factors. PD-L1 positivity was seen in cases with advanced pathological features, which suggest its role in the tumorigenesis of gastric and gastroesophageal junction adenocarcinoma. Her2neu positivity showed no correlation with advanced pathological features as well as no prognostic significance, which could be attributed to tumor heterogeneity, endoscopic nature of the biopsies, and non-confirmation of equivocal cases by fluorescent in situ hybridization.

Keywords: Gastric adenocarcinoma; Her2neu; Immunohistochemistry; PD-L1.