Diameter of involved nerves is a valuable prognostic factor for gastric cancer.

The prognostic role of perineural invasion (PNI) in gastric cancer remains unclear. We hypothesized that the diameter of the tumor-involved nerves might be a useful indicator for prognosis. By labeling nerves and cancer cells in 204 cases of gastric cancer with single or double immunochemistry, we found that 146 cases were PNI positive and that 58 were PNI negative. For each case with PNI, the maximum diameter of the involved nerve was measured microscopically. Then, we correlated this parameter with the patients' 5-year overall survival, and receiver operating curves were used to determine the cutoff value. We found that the optimal cutoff value for predicting 5-year survival was 65 µm (sensitivity 76.9%, specificity 70.0%). Next, all 204 patients were classified into two groups as follows: Group A, PNI-positive cases in which the largest involved nerves were ≥65 µm in diameter (110 cases); Group B, PNI-positive cases in which the largest involved nerves were P˂65 µm and all PNI-negative cases (94 cases). Compared with Group A, Group B had a better 5-year survival (74.5% vs 27.3%) and a better 5-year disease-free survival (63.8% vs 23.6%). Multivariate analysis suggested that a ≥65 µm maximum diameter of the involved nerves was an independent risk factor for both recurrence (P˂0.001) and gastric cancer-related death (P˂0.001) within 5 years. However, if all patients were classified simply based on whether PNI existed (regardless of the nerve size), this did not provide more information than traditional clinicopathological variables. In conclusion, the presence of cancer-involved nerves with a diameter ≥65 µm was a valuable prognostic factor for gastric cancer.

Reevaluating significance of perineural invasion in gastric cancer based on double immunohistochemical staining.

CONTEXT: In gastric cancer, the significance of perineural invasion remains controversial. Detecting perineural invasion with hematoxylin-eosin staining often leads to misdiagnosis. Labeling nerves by immunohistochemistry greatly assists perineural invasion detection, but it might also be misdiagnosed, because scattered cancer cells are difficult to recognize. OBJECTIVE: To reevaluate the significance of perineural invasion in gastric cancer by double immunohistochemical staining that labels both nerves and cancer cells, and to examine agreements on perineural invasion detection between double immunohistochemical staining and single immunochemical staining (to label nerves) or hematoxylin-eosin staining. DESIGN: We evaluated perineural invasion in 160 cases of gastric cancer with double immunohistochemical staining, single immunochemical staining, and hematoxylin-eosin staining, respectively; then we investigated the prognostic significance of perineural invasion. RESULTS: Perineural invasion was detected in 65.0% (104 of 160), 38.1% (61 of 160), and 56.9% (91 of 160) of cases with double immunohistochemical staining, hematoxylin-eosin staining, and single immunohistochemical staining, respectively. Agreement was low between double staining and hematoxylin-eosin staining (κ = .34), and most false reports occurred in diffuse gastric cancer. Agreement between single immunochemical staining and double staining was good (κ = .67), but it declined in diffuse gastric cancer (κ = .28). Perineural invasion was closely associated with other clinicopathologic variables. Although perineural invasion-positive patients had a worse outcome than perineural invasion-negative patients, it was not an independent prognostic factor (P = .11; hazard ratio, 0.637; 95% confidence interval, 0.366-1.110). CONCLUSIONS: Double immunohistochemical staining could improve accuracy of perineural invasion detection in gastric cancer, particularly in the diffuse type. Moreover, perineural invasion predicts a poor outcome in gastric cancer, but it cannot provide more information than traditional clinicopathologic variables.