Patients presenting to the Department of Surgery meeting the inclusion criteria will be assessed. After the written informed consent, patients will be enrolled in the study. The clinical and demographic data will be collected prospectively using a specified proforma. The details of the investigations carried out as a standard of care for the diagnosis and staging will be recorded in the data collection proforma which includes the Contrast-enhanced Computed Tomography of the abdomen and pelvis (thorax if indicated) and blood investigations including serum biomarkers viz.  CEA, Neutrophil Lymphocytic Ratio.

All patients will undergo Upper Gastrointestinal endoscopy and guided biopsy (Ten tissue bits from the tumour), which is as per recommended guidelines, to confirm the diagnosis and for determining the histopathological characteristics. The location of the tumor and the presence of Barrette’s esophagus changes will be recorded in the proforma. The tumour tissue samples taken from the endoscopically guided biopsy will also be subjected to the testing of various tumour biomarkers which include HER2Neu, p53, E cadherin, MLH1, and PDL1 by Immunohistochemistry on the tissue sample obtained.

The expression of these biomarkers is graded based on the percentage of tumor cell nuclear (p53) and membranous (for Her2neu) staining and the staining intensity.¹⁹ The immunoreactivity for p53 antibody will be scored as the percentage of positively stained nuclei by counting 100–200 (minimum 100) tumour cells²⁰. The immune-expression of E cadherin levels will be dichotomized into negative expression and positive expression (1 =≤10, 2=>10 and ≤ 50%, 3>50%). The raw data will be converted to an immunohistochemical score (IHC) by multiplying the quantity and intensity scores. An IHC score of 9 to 12 will be considered as strong immunoreactivity (+++), 5 to 8 as moderate (++), 1 to 4 as weak (+), and 0 as negative (-). Cases with a score of less than 1 will be considered as negative, and those with ≥1 regarded as positive.

Immunohistochemistry with anti-PDL1 antibody is regarded as positive if more than 5% of the cancer cells show membranous staining.

After the investigations and imaging, patients will be managed as per the standard protocol by the treating surgeon and will undergo curative resection/ palliative resection/ palliative by-pass or neoadjuvant chemotherapy. The type of surgery (total gastrctomy/ subtotal gastrectomy/ palliative resection or by-pass) and the postoperative histopathological details (margin status R0/R1/R2, Tumour and Nodal charecteresitics, histopathological grade, Lauren’s type, routine IHC markers etc). The patients will be followed up after surgery and the postoperative histopathology will be discussed in the tumour board for requirement of adjuvant chemotherapy and any targeted therapy. After the adjuvant therapy, patients will be followed up every three months for first two years and every six monthly during the subsequent years till the completion of the study. In each visit, the clinical examination, blood investigation and imaging etc. will be carried as per the standard protocol. Any recurrence during the follow up will be noted in detail in the proforma. Mortality during any stage of the treatment or follow up will be recorded along with the cause of mortality and the terminal course.