Abstract: Objective This study aimed to investigate the expression of Claudin 18.2 and mean vascular density (MVD) in invasive breast cancer (IBC) and their correlation with clinicopathological parameters. Furthermore,we analyzed the relationship between Claudin 18.2 and MVD,and assess their potential application value in breast cancer diagnosis and prognosis evaluation. Methods A total of 78 paraffin-embedded IBC tissue blocks achieved from the Pathology Department of Zhengzhou People’s Hospital from January 2017 to June 2018 were selected,and 27 benign breast lesion tissue samples were selected from the same period. The expression of Claudin 18.2 and CD34 were detected by immunohistochemical SP method. The expression of Claudin 18.2 protein was quantitatively analyzed using ImagePro Plus (IPP) image analysis software,while the number of CD34-positive vessels in five high-power fields were counted with their average was calculated to represent MVD. The relationships between the expression levels of Claudin 18.2 and MVD with clinicopathological features such as age,location,and WHO grade were analyzed. Spearman’s correlation analysis was performed to examine the correlation between Claudin 18.2 and MVD. Results Claudin 18.2 was mainly localized to the cell membrane of IBC,while CD34 mainly labeled blood vessels within the stroma surrounding cancer nests. The expression of Claudin 18.2 protein and MVD in IBC tissues were significantly upregulated compared with those in benign breast lesion tissues (P=0.000). The expression of Claudin 18.2 protein was significantly higher in WHO grade III (12.49±5.97) than in grades I-II (10.26±3.94),and higher in cases with lymph node metastasis (12.65±5.91) than those without (10.22±4.00) (P< 0.05 for both). The MVD value was higher in WHO grade III (48.88±49.40) than in grades I-II (32.05±21.36),higher in the low progesterone receptor (PR) expression group (43.61±44.30) than in the high expression group (32.72±21.17),and significantly higher in the HER2 amplified group (50.82±51.18) than in the non-amplified group (34.82±28.90) (P< 0.05 for all). Spearman correlation analysis revealed a significant positive correlation between Claudin 18.2 and MVD in IBC tissues (r=0.973,P=0.000). Conclusion The high expression of Claudin 18.2 and MVD in IBC is closely related to the occurrence and development of tumors,and there is a significant positive correlation between them. The quantitative detection of Claudin 18.2 protein expression and MVD are of great clinical significance for assessing breast cancer invasion and metastasis,providing a reference for pathological diagnosis,individualized treatment,and prognosis evaluation of IBC.