PCR versus histology for detection of Helicobacter pylori in gastric biopsies: increased sensitivity of molecular...

Accurate diagnosis of Helicobacter pylori infections is essential for timely eradication; however, histopathological diagnostic performance is limited in some cases such as patchy mucosal colonization. This retrospective study evaluated the diagnostic yield of PCR in archived formalin-fixed, paraffin-embedded (FFPE) gastric biopsy specimens previously evaluated by histology, and compared endoscopic, histologic, and clinical characteristics of histology-negative/PCR-positive and histology-positive/PCR-positive cases.

FFPE gastric biopsies (n = 830), obtained during routine esophagogastroduodenoscopy, were retrospectively analyzed by PCR. Histology, rapid urease test (RUT), culture, and immunohistochemistry (IHC) data were retrieved from clinical records. PCR band intensity was quantified using ImageJ.

PCR identified 77.5% specimens as H. pylori-positive. Among the 476 histology-negative specimens, 63.4% were PCR-positive. Compared with histology, PCR sensitivity was 96.3% (95% CI 93.8-97.8) and specificity was 36.6% (95% CI 32.4-41.0). Histology-negative/PCR-positive cases showed significantly lower RUT positivity (14.7% vs. 92.5%, p < 0.001), endoscopy-detected gastritis (48.0% vs. 64.5%, p < 0.001), nodularity (13.2% vs. 34.6%, p < 0.001) and PCR band intensity (p < 0.001), and markedly reduced histology-detected gastritis (46.1% vs. 100.0%, p < 0.001) and active gastritis (14.2% vs. 86.8%, p < 0.001), consistent with lower bacterial burden.

Retrospective PCR analysis of FFPE gastric biopsies identified a substantial proportion of H. pylori infections missed by routine histology, particularly in cases with reduced bacterial density and minimal inflammatory activity. These findings support PCR as a sensitive complementary tool for H. pylori diagnosis while underscoring the importance of interpreting molecular results within their full clinicopathologic context.