Gastric Cancer Diagnostics

Laboratory Tests and Ancillaries

Routine Blood Tests

Routine blood tests include complete blood count (CBC), differential count, and liver and renal function tests. This is done to check for evidence of iron-deficiency anemia and to determine appropriate treatment options.

Immunohistochemistry (IHC)

Immunohistochemistry is a recommended test for the assessment of HER2 overexpression. This evaluates the membranous immunostaining of the tumor cells, including intensity and the extent of staining and percentage of immunoreactive tumor cells, with scores ranging from 0 to 3+. A score of 0 or 1+ means negative for HER2 expression. A score of 2+ is equivocal and needs to have FISH for confirmation.

Fluorescence in situ Hybridization (FISH)

Fluorescence in situ hybridization is done to verify results of HER2 testing that are considered equivocal by IHC.

Tumor Markers

Microsatellite instability (MSI) testing through polymerase chain reaction (PCR) or next-generation sequencing (NGS), or mismatch repair (MMR) testing through immunohistochemistry is recommended for all newly diagnosed gastric cancer. These are performed only in certified laboratories. Next-generation sequencing is a test that is able to detect numerous mutations simultaneously. This is an alternative test for the identification of HER2 amplification, microsatellite instability status, mismatch repair deficiency, tumor mutational burden (TMB) and neurotrophic tropomysin-related kinase (NTRK) gene fusions in patients unable to undergo traditional biopsy or when limited tissue is available for testing. These must be performed in a certified laboratory. HER2 and programmed death ligand 1 (PD-L1) expression is recommended for all patients with gastric adenocarcinoma if metastatic adenocarcinoma is suspected or documented. HER2 testing is recommended if therapy with Trastuzumab is being considered for patients with inoperable locally advanced, recurrent or metastatic gastric adenocarcinoma. PD-L1 testing should be considered for patients with locally advanced, recurrent, or metastatic gastric adenocarcinoma and possible candidates for PD-1 inhibitor therapy. NTRK gene fusion testing should be considered for patients who are possible candidates for TRK inhibitor therapy. Other markers being investigated for gastric cancer diagnosis include FGFR2 amplification/overexpression, MET amplification, claudin (CLDN)-18.2 overexpression and Epstein-Barr virus.

Liquid Biopsy

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Imaging

Diagnostic and Staging Investigations  

Upper Endoscopy  

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Upper endoscopy is also called esophagogastroduodenoscopy or EGD. Gastric cancer appears like an ulcer, a mushroom-shaped or protruding mass or diffuse, flat, thickened areas of mucosa known as linitis plastica. This is performed to determine the presence and location of gastric cancer and to biopsy any suspicious lesions.

Gastroscopic or Surgical Biopsy

Gastroscopic or surgical biopsy is done to diagnose, classify histologically, and identify the status of molecular biomarkers (eg human epidermal growth factor receptor-2 [HER2]). Multiple (6-8) biopsies using standard-size endoscopy forceps are required to provide sufficient specimen for histologic examination.

Endoscopic Ultrasound

Endoscopic ultrasound is done to determine the depth of the tumor invasions (T and N stages), although it is less useful in antral tumors. This provides an accurate initial clinical staging of locoregional gastric cancer. This is a preferred modality if early-stage cancer is suspected or to determine early versus locally advanced disease. Endoscopic ultrasound is done to identify perigastric lymph nodes and the presence of malignant or inflammatory lymph nodes. These nodes appear as enlarged, hypoechoic (dark), homogenous, well-circumscribed, rounded structures. This is done to diagnose submucosal tumors, and to differentiate potentially malignant lesions, endoscopic ultrasound with fine needle aspiration biopsy is done.

Laparoscopic Staging with Peritoneal Washings for Cytology

Laparoscopic staging with peritoneal washings for cytology is done to exclude metastatic disease involving the diaphragm/peritoneum. This is indicated for patients with clinical stages ≥T1b gastric cancers. This is recommended for evaluation of peritoneal spread when surgery or chemoradiation is being considered for medically fit patients with resectable locoregional cancer. This may be considered in medically fit patients with unresectable locoregional cancer. This should be considered in patients receiving preoperative therapy. This may be useful in patients with T3 and/or N+ gastric cancers who are being considered for surgical resection without preoperative therapy. Peritoneal fluid cytology testing may help to improve staging through identification of occult carcinomatosis. Positive peritoneal cytology is associated with poor prognosis and is an independent predictor for identifying patients who are at higher risk for recurrence following curative resection. Laparoscopic lavage cytology is also very useful to identify a subset of patients with M1 disease who are unlikely to benefit from resection alone.

Positron Emission Tomography (PET) Scan

In some cases, a positron emission tomography scan improves detection of occult metastatic disease.

Computed Tomography (CT) Scans

Computed tomography scan is routinely used for preoperative staging. CT scans of the chest, abdomen, and pelvis are recommended for all gastric cancer patients before surgery to evaluate for disease extent and degree of lymph node involvement. This must be performed in medically fit patients after preoperative chemotherapy or chemoradiation completion and before surgical intervention. This is used for restaging of non-surgical candidates after primary treatment. This is done to predict response to preoperative chemotherapy as well as in the evaluation of recurrent gastric cancer.