Her4 in gastric adenocarcinoma and its association with molecular prognostic markers Ki-67 proliferation index and p53 mutational status in Saudis: A study at a tertiary care hospital in Eastern Saudi Arabia

BACKGROUND: Gastric cancer is the fifth most common and third leading cause of cancer death worldwide. Her4 receptor has proapoptotic and antiproliferative activity. The role of Her4 in gastric carcinogenesis and its prognostic implications have not been much investigated, as evidenced by the paucity of overall and Saudi regional-based studies. This study aimed to highlight the expression of Her4 in gastric adenocarcinoma (GA) as well as its association with clinicopathological parameters and molecular prognostic markers Ki-67 and p53 in a Saudi cohort. MATERIALS AND METHODS: In this descriptive cross-sectional study, data were retrospectively obtained by selecting all cases of GA from 2012 to 2022, for which Her4 immunohistochemical (IHC) analysis was done by total population sampling technique from the Pathology Department archives of King Fahd Hospital of the University, Al-Khobar, Saudi Arabia. Patients’ demographic and clinicopathological profile, Lauren’s histological classification, and IHC data for Ki-67, p53, and Her2-neu were also retrieved. Her4 positivity was recalibrated and its association with clinicopathological parameters, Ki-67, p53 and Her2-neu was determined. Data analysis performed using SPSS; Chi-square test assessed the relationship between Ki-67 proliferation index and p53 mutation status in Her4-negative cases. RESULTS: Out of the 50 cases of GA selected, Her4-positive cases were 22% (n = 11), and in these Her4-positive cases, 63.6% had intestinal-type morphology, 54.5% were high-grade tumors, male preponderance was 63.6%, the median age was 73 years, and the mean age was 74 years (standard deviation [SD]: 9.3). 3 + positivity was seen at the mean age of 69 years (SD: 14.6), but there was one case at 53 years. A high Ki-67 proliferation index was present in 63.6% and a predominant aberrant/mutational p53 mutation status in 54.4% of the cases. CONCLUSION: Her4 frequency of 22% is lower than other reported studies underlining the concept of geographical and ethnic variation in intrinsic tumor properties. Her4 expression with a higher tumor grade, high Ki-67 proliferation index, and aberrant/mutational p53 status imparts an aggressive tumor characteristic to this set of GA cases.