Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

Abstract

BACKGROUND Although the role of p53 in the evolution and prognosis of gastric cancer (GC) has been extensively examined, the exact mechanism of action is incompletely understood. In the last years, p53-target genes were supposed to be involved in the p53 pathway. One of them is the tumor-suppressor gene Maspin, which codifies the protein with the same name. Maspin activity depends on its subcellular localization. To our knowledge, the possible role of TP53 gene in Maspin subcellular localization, in GC cells, has not yet been studied in a large number of human samples. AIM To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization. METHODS The present study included 266 consecutive patients with GC in which TP53 gene status, and mutations in exons 2 to 11, respectively, were analyzed and correlated with immunohistochemical expression of p53 and Maspin. RESULTS None of the 266 cases showed mutations in exon 9. The rate of TP53 mutations was 33.83%. The mutation rate was slightly higher in distally-located GCs, with a lower degree (≤ 5 buds/ high power fields) of dyscohesivity ( P < 0.01). The wild-type cases had a longer survival, compared with mutant GCs, especially in patients without lymph node metastases, despite the high depth of tumor infiltration ( P = 0.01). The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value ( P < 0.01). The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells. CONCLUSION Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression. These findings should be proved in experimental studies.

Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity in tumor‑related genes in gastric cancer

“…The results indicated that, although recommended as classic markers in CRC, not all of the five loci in the B5 panel were sensitive to MSI in GC. In addition, TP53-1 was considered to be the most LOH-prone locus, which was in line with a previous study, which suggested that TP53 was the most mutated gene (18).…”

“…It is well-known that the alteration of tumor-related genes, such as the inactivation of tumor suppressor (TS) genes and the amplification of oncogenes, is a main factor in GC development ( 18 , 19 ). On the other hand, MSs are frequently used as markers for the detection of loss of heterozygosity (LOH), which has been associated with GC progression ( 20 ).…”

Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

“…Deletion of TP53 may upregulate vascular endothelial growth factor A (VEGF-A) expression and promote cancer cell angiogenesis, leading to a poor prognosis ( 36 ). Gurzu et al ( 37 ) analyzed a large number of human gastric cancer samples and found that mutation of exon 7 in TP53 may induce downregulation of the expression of the tumor suppressor gene Maspin, which leads to GC invasion and metastasis. In addition, TP53 mutations induce hypoxic signaling ( 38 ) and inhibit antitumor immunity ( 39 ).…”

Subcellular Expression of Maspin in Colorectal Cancer: Friend or Foe

“…Maspin is a p53-target gene which also depends on the microsatellite status of the tumor cells [1,15,19,20]. In gastric carcinomas, we proved that loss of maspin might be induced by TP53 gene mutations in exon 7 whereas wild-type p53 was hypothesized to be responsible by restoration of the nuclear maspin expression and further decreasing of the metastatic potential [20].…”