Combined detection of P53, Ki67, P504S, and IMP3: Diagnostic implications for gastric cancer and precursor lesions

Differential diagnosis among atypical hyperplasia (AH) (including reparative hyperplasia and intestinal metaplasia), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinoma (AC) in gastric mucosal biopsies is challenging due to histomorphological overlaps, variability in pathological diagnosis consistency, and limited reproducibility.

To evaluate the diagnostic utility of P53, Ki67, P504S, and IMP3 in gastric cancer and its precancerous lesions, focusing on their effectiveness in distinguishing AH, LGD, HGD, and AC.

From January 2018 to September 2020, a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors (2019). The specimens were categorized into four groups: AH, LGD, HGD, and AC. Immunohistochemistry was employed to assess the expression status of P53, Ki67, P504S, and IMP3. Intergroup comparisons were performed using the χ ² test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.

The expression rate of P504S was highest in the LGD group (53.3%, 16/30), while IMP3 expression was highest in the AC group (41.9%, 26/62), followed by the HGD group (33.3%). Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups (P < 0.001). Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD, HGD, and AC groups (P < 0.001), as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups, and between the LGD group and the HGD and AC groups (P < 0.001). Additionally, significant correlations were found between P504S and the polarity expression pattern of Ki67, and between IMP3 and the mutation expression pattern of P53 (P < 0.001). The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC, respectively.

P504S is highly expressed in LGD and is associated with the Ki67 "polarity" expression pattern. IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern. The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC, respectively. The rational use of P504S, Ki67, IMP3, and p53 can help distinguish gastric cancer and precancerous lesions, improving the early cancer diagnosis rate.