Genomically Silent Refractory Gastric Cancer in a Young Patient Exhibits Overexpression of CXCL5

Abstract

Gastric cancer is the third leading cause of cancer-related deaths, with more than one million new cases and approximately 841,000 deaths annually worldwide. We report a case of a young patient (25 years old) with an aggressive form of gastric cancer. The patient had previously been treated for Helicobacter pylori (H. pylori), which is a main risk factor for developing gastric cancer. Genetic testing showed an E-cadherin (CDH1) germline mutation of unknown significance. After eight cycles of chemotherapy, a positron emission tomography (PET) scan showed disease progression with an enlarging hypermetabolic right adnexal mass suspicious for metastatic disease. Tumor pathology demonstrated invasive and poorly differentiated gastric carcinoma. The analysis of the tumor biopsy indicated the very high expression of a chemokine, C-X-C motif chemokine 5 (CXCL5). The combination of H. pylori infection with an existence of a rare CDH1 mutation could have contributed to this aggressive gastric cancer.

Keywords: CDH1; CXCL5; Helicobacter pylori; advanced gastric cancer; young patient.

Figure 1

Computed tomography (CT)/positron emission tomography (PET) scan of patient demonstrated moderate focal uptake along gastric body consistent with known malignancy (yellow arrow in panel (A,B)). There was also a large, mildly hypermetabolic right adnexal area with heterogenous uptake concerning for metastatic involvement (yellow circle). Kidneys (blue arrows) and bladder (orange arrow) demonstrate physiologic uptake.

Figure 2

Hematoxylin and eosin staining revealed invasive, poorly differentiated gastric carcinoma invading into the muscularis propriawith minimal gland formation (panel (A),2× magnification). Panel (B) (20× magnification) demonstrates signet ring cell component (blue arrow) as well as pleomorphic neoplastic cells (red arrow).

Figure 3

Axial CT image of case report patient demonstrated disease recurrence in left abdominal wall (yellow arrow).

Figure 4

CXCL5 was overexpressed in the gastric biopsy of the case patient. CXCL5 expression in 13 other gastric biopsies is shown for comparison. CXCL5 expression was quantified via qRT-PCR and expressed relative to GAPDH using comparative cycle threshold calculations (ΔC_T, Applied Biosystems). 2PN, paired normal control of case patient (2T); T, tumor gastric cancer tissue.